1.Endometriosis and thyroid cancer:a two-sample mendelian randomization analysis
Yican SHANG ; Chenyu XIONG ; Yanhui HUANG
Journal of Clinical Medicine in Practice 2025;29(10):14-18,25
Objective To investigate the bidirectional causal relationship between endometriosis and thyroid cancer using bidirectional two-sample Mendelian randomization(MR).Methods Ge-nome-wide association study(GWAS)data for endometriosis were obtained from the FinnGen R11 database,and GWAS data for thyroid cancer were sourced from the European Bioinformatics Institute(EMBL-EBI).Single nucleotide polymorphisms(SNPs)that met the requirements were selected as instrumental variables.The inverse variance weighted(IVW)method was employed as the primary analytical approach,supplemented by MR-Egger regression,weighted median method,simple model,and weighted model results.Cochran's Q test,MR-Egger regression intercept analysis,and the leave-one-out method were used to assess the robustness of the results.Results Ultimately,25 SNPs high-ly associated with endometriosis and 3 SNPs highly associated with thyroid cancer were included in this study.The IVW analysis results of the forward MR analysis indicated no significant causal rela-tionship between endometriosis and the risk of thyroid cancer(P=0.50,OR=1.06,95%CI:0.88 to 1.29).This result was also supported by MR-Egger regression,simple model,weighted model,and weighted median analyses(P>0.05).The IVW analysis results of the reverse MR analysis similarly showed no significant causal relationship between thyroid cancer and the risk of endometrio-sis(P=0.09,OR=1.03,95%CI,0.99 to 1.06).The findings from MR-Egger regression,sim-ple model,weighted model,and weighted median analyses all supported this conclusion(P>0.05).Conclusion The MR analysis doesn't show a significant bidirectional causal relationship between endometriosis and thyroid cancer.
2.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
3.AKT1-mediated autophagy of hepatocellular carcinoma cells enhances cell sensitivity to 125I seed irradiation
Chenyu WANG ; Zhizhou WU ; Li LIU ; Yunhua XIAO ; Xuequan HUANG
Journal of Army Medical University 2025;47(6):539-550
Objective To investigate the impact of serine/threonine-protein kinase 1(AKT1)-mediated autophagy in hepatocellular carcinoma(HCC)cells on their sensitivity to 125I seed irradiation.Methods ① iProX database and STRING12.0 website were utilized to analyze the proteomic data of HCC before and after 125I seed irradiation to explore the differentially expressed proteins and associated functional connections.Meanwhile,The Cancer Genomics Atlas(TCGA)database was employed to analyze the relationship between AKT1 expression level and the survival of HCC patients.② Human HCC cell lines HUH7 and Hep3B were exposed to continuous irradiation from 125I radioactive seeds with an initial apparent activity of 0.8 mCi per seed for approximately 120 h,accumulating a total dose of 8 Gy,while the control cells were cultured under normal condition for 120 h.③ Autophagy inhibitor,chloroquine(CQ)and inducer,rapamycin(RAPA)were used to treat the HCC cells respectively to establish the CQ group and the RAPA group.The lentiviral transfection technique was employed to construct the HCC cells with overexpressed AKT1,namely the AKT1 group.The HCC cells treated in the same way were continuously irradiated with 125I seeds for 120 h to construct the CQ+125I group,the RAPA+125I group,and the AKT1+125I group.④The changes in microtubule-associated protein light chain 3(LC3),p62,AKT1 and p-AKT1 were detected by Western blotting.Cell immunofluorescence assay was employed to observe the expression of autophagy related proteins,such as LC3.The colony forming ability and apoptotic rate were detected with plate cloning assay and flow cytometry.Results ① Continuous irradiation with 125I seeds resulted in decreased expression of p62 and increased ratio of LC3Ⅱ/LC3Ⅰ(P<0.05)when compared with the negative control(NC)group.Immunofluorescence assay revealed more green fluorescence spots of LC3.When compared with the 125I group,the CQ+125I group had significantly increased expression of p62(P<0.01),decreased ratio of LC3Ⅱ/LC3Ⅰ(P<0.01),lower apoptotic rate(P<0.01),and more colony formations(P<0.01).In contrast,the results in the RAPA+125I group were opposite to those of the CQ+125I group.② Analysis on the iProX database showed that the expression of AKT1 was decreased in the irradiated group,and analysis on the TCGA database indicated that high expression of AKT1 predicted a poor prognosis for HCC patients(P<0.01).③After irradiation with 125I seeds,the expression of AKT1 at both the RNA and protein levels was decreased in the 125I group(P<0.01).After overexpression of AKT1,the level of autophagy was decreased(P<0.05).Irradiation of HCC cells with overexpressed AKT1 using 125I seeds could partially restore the level of autophagy.In the AKT1+125I group,the expression of AKT1,pAKT1 and p62 were all decreased,and the ratio of LC3Ⅱ/LC3Ⅰwas increased than the AKT1 group(P<0.05).④ The apoptotic rate of the AKT1+125I group was lower than that of the 125I group(P<0.05)and higher than that in the AKT1 group(P<0.05).In HUH7 cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group(P<0.05).In Hep3B cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group,and the clonogenic ability of the AKT1 group was higher than that of the NC group(P<0.05).Conclusion 125I seed irradiation induce lethal autophagy in HCC cells by reducing the expression of AKT1,providing a new theoretical basis for the implantation of 125I radioactive seeds in the treatment of HCC.
4.Phase Change and Quantity-quality Transfer Analysis of Medicinal Materials, Decoction Pieces and Standard Decoction of Haliotidis Concha (Haliotis discus hannai)
Zhihan YANG ; Jingwei ZHOU ; Weichao WANG ; Yu HUANG ; Chuang LUO ; Lian YANG ; Chenyu ZHONG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):206-214
ObjectiveTo explore the quantity-quality transfer process of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(Haliotis discus hannai) by analyzing the physical phase and compositional changes, so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha(H. discus hannai) from different habitats were collected and prepared into corresponding calcined products and standard decoction, and the content of CaCO3 of the three samples were determined and the extract yield and transfer rate of CaCO3 were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry(XRF), X-ray diffraction(XRD) was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry(FTIR) was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram, while combining hierarchical cluster analysis(HCA), principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) to find the common and differential characteristics, in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha(H. discus hannai). ResultsThe CaCO3 contents of the 20 batches of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(H. discus hannai) were 93.87%-98.95%, 96.02%-99.97% and 38.29%-51.96%, respectively, and the extract yield of standard decoction was 1.71%-2.37%, and the CaCO3 transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity, and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction, the difference in the relative contents was obvious, which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO3 of aragonite and calcite, while calcined Haliotidis Concha only contained CaCO3 of calcite, and standard decoction mainly contained CaCO3 of calcite and Na2CO3 of natrite. FTIR results showed that there were internal vibrations of O-H, C-H, C=O, HCO3- and CO32- groups in Haliotidis Concha, while O-H, HCO3- and CO32- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO3 content, the transformation of CaCO3 aragonite crystal form to calcite crystal form and the absence of organic components after calcination, and the changes of calcined products and standard decoction are mainly the decrease of CaCO3 content and the increase of Na2CO3 relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction, which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.
5.Phase Change and Quantity-quality Transfer Analysis of Medicinal Materials, Decoction Pieces and Standard Decoction of Haliotidis Concha (Haliotis discus hannai)
Zhihan YANG ; Jingwei ZHOU ; Weichao WANG ; Yu HUANG ; Chuang LUO ; Lian YANG ; Chenyu ZHONG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):206-214
ObjectiveTo explore the quantity-quality transfer process of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(Haliotis discus hannai) by analyzing the physical phase and compositional changes, so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha(H. discus hannai) from different habitats were collected and prepared into corresponding calcined products and standard decoction, and the content of CaCO3 of the three samples were determined and the extract yield and transfer rate of CaCO3 were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry(XRF), X-ray diffraction(XRD) was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry(FTIR) was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram, while combining hierarchical cluster analysis(HCA), principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) to find the common and differential characteristics, in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha(H. discus hannai). ResultsThe CaCO3 contents of the 20 batches of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(H. discus hannai) were 93.87%-98.95%, 96.02%-99.97% and 38.29%-51.96%, respectively, and the extract yield of standard decoction was 1.71%-2.37%, and the CaCO3 transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity, and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction, the difference in the relative contents was obvious, which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO3 of aragonite and calcite, while calcined Haliotidis Concha only contained CaCO3 of calcite, and standard decoction mainly contained CaCO3 of calcite and Na2CO3 of natrite. FTIR results showed that there were internal vibrations of O-H, C-H, C=O, HCO3- and CO32- groups in Haliotidis Concha, while O-H, HCO3- and CO32- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO3 content, the transformation of CaCO3 aragonite crystal form to calcite crystal form and the absence of organic components after calcination, and the changes of calcined products and standard decoction are mainly the decrease of CaCO3 content and the increase of Na2CO3 relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction, which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.
6.Antimicrobial resistance surveillance in the bacterial strains isolated from pediatric intensive care units in China:results from 2020 to 2022
Jing LIU ; Huiyuan YAN ; Gangfeng YAN ; Guoping LU ; Pan FU ; Chuanqing WANG ; Danqun JIN ; Wenjia TONG ; Chenyu ZHANG ; Jianli CHEN ; Yi LIN ; Jia LEI ; Yibing CHENG ; Qunqun ZHANG ; Kaijie GAO ; Yuanyuan CHEN ; Shufang XIAO ; Juan HE ; Li JIANG ; Huimin XU ; Yuxia LI ; Hanghai DING ; Hehe CHEN ; Yao ZHENG ; Qunying CHEN ; Ying WANG ; Hong REN ; Chenmei ZHANG ; Zhenjie CHEN ; Mingming ZHOU ; Yucai ZHANG ; Yiping ZHOU ; Zhenjiang BAI ; Saihu HUANG ; Lili HUANG ; Weiguo YANG ; Weike MA ; Qing MENG ; Pengwei ZHU ; Yong LI ; Yan XU ; Yi WANG ; Yanqiang DU ; Huijun CAI ; Bizhen ZHU ; Huixuan SHI ; Shaoxian HONG ; Yukun HUANG ; Meilian HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):303-311
Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2%)and gram-negative organisms(60.8%).The top three organisms were S.aureus(13.6%,1 453/10 688),A.baumannii(10.0%,1 067/10 688),and coagulase-negative Staphylococcus(9.9%,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1%,19.4%,8.8%,30.9%,67.4%,and 28.8%,respectively.Overall,more than 50%of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25%of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80%of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3%in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.
7.Functional Connectivity of Lower Limb Sensorimotor Cortex in Type 2 Diabetic Peripheral Neuropathy via Resting-State fMRI
Yitong GUAN ; Wanting LIU ; Peichun PAN ; Jing LI ; Chenyu ZHANG ; Yang HUANG ; Dongsheng ZHANG ; Xiaoling ZHANG
Chinese Journal of Medical Imaging 2025;33(8):805-810
Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.
8.Functional Connectivity of Lower Limb Sensorimotor Cortex in Type 2 Diabetic Peripheral Neuropathy via Resting-State fMRI
Yitong GUAN ; Wanting LIU ; Peichun PAN ; Jing LI ; Chenyu ZHANG ; Yang HUANG ; Dongsheng ZHANG ; Xiaoling ZHANG
Chinese Journal of Medical Imaging 2025;33(8):805-810
Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.
9.Antimicrobial resistance surveillance in the bacterial strains isolated from pediatric intensive care units in China:results from 2020 to 2022
Jing LIU ; Huiyuan YAN ; Gangfeng YAN ; Guoping LU ; Pan FU ; Chuanqing WANG ; Danqun JIN ; Wenjia TONG ; Chenyu ZHANG ; Jianli CHEN ; Yi LIN ; Jia LEI ; Yibing CHENG ; Qunqun ZHANG ; Kaijie GAO ; Yuanyuan CHEN ; Shufang XIAO ; Juan HE ; Li JIANG ; Huimin XU ; Yuxia LI ; Hanghai DING ; Hehe CHEN ; Yao ZHENG ; Qunying CHEN ; Ying WANG ; Hong REN ; Chenmei ZHANG ; Zhenjie CHEN ; Mingming ZHOU ; Yucai ZHANG ; Yiping ZHOU ; Zhenjiang BAI ; Saihu HUANG ; Lili HUANG ; Weiguo YANG ; Weike MA ; Qing MENG ; Pengwei ZHU ; Yong LI ; Yan XU ; Yi WANG ; Yanqiang DU ; Huijun CAI ; Bizhen ZHU ; Huixuan SHI ; Shaoxian HONG ; Yukun HUANG ; Meilian HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):303-311
Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2%)and gram-negative organisms(60.8%).The top three organisms were S.aureus(13.6%,1 453/10 688),A.baumannii(10.0%,1 067/10 688),and coagulase-negative Staphylococcus(9.9%,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1%,19.4%,8.8%,30.9%,67.4%,and 28.8%,respectively.Overall,more than 50%of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25%of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80%of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3%in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.
10.Effect of ligustrazine on learning and memory function of rats with aluminum-induced cognitive im-pairment and its mechanism
Chenyu LI ; Yunjing JIA ; Qiushengxi ZHANG ; Zuozhu HUANG ; Yang LIU ; Yanwu LING
Journal of Xinxiang Medical College 2024;41(9):801-808
Objective To explore the effect of ligustrazine on the learning and memory function of rats with aluminum-induced cognitive impairment and its mechanism.Methods Sixty male Wistar rats were divided into a blank control group,a model group,a low-dose ligustrazine group,a high-dose ligustrazine group,and a piracetam group using a random number table method,with 12 rats in each group.The rats in the blank control group were not subjected to any treatment;the rats in the model group,low-dose ligustrazine group,high-dose ligustrazine group,and piracetam group were first prepared with aluminum toxicity models by daily gavage of 100 mg·kg-1 AlCl3 solution.After successful modeling,the rats in the piracetam group were intragastrically administered with piracetam at a dose of 400 mg·kg-1,while rats in the low-dose and high-dose ligustrazine groups were intragastrically administered with 100 and 200 mg·kg-1 ligustrazine,respectively;the rats in the blank control group and the model group were intragastrically administered with the same volume of physiological saline.All rats in the five groups received intragas tric administration once a day for 30 consecutive days.After 30 days of intervention,the Morris water maze test was used to evaluate the learning and memory function of rats in the five groups.After completing the water maze experiment,rats in the five groups were anesthetized with 200 g·L-1 chloral hydrate,and their brain tissues were quickly removed after decapitation.Immunohistochemical staining was used to observe the expression of calcium voltage-gated channel subunit alpha 1E(CACNA1E),calmodulin(CALM),and brain-derived neurotrophic factor(BDNF)in the hippocampal CA1 region of rats in the five groups;Western blot was used to detect the relative expression levels of CACNA1E,CALM,and BDNF proteins in the hippocampal CA1 region of rats in the five groups;and real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of CACNA1E,CALM,and BDNF mRNA in the hippocampal CA1 region of rats in the five groups.Results On the 1st day of the Morris water maze test,the latent periods of rats in the model group,piracetam group,low-dose ligustrazine group,and high-dose ligustrazine group were significantly higher than those in the blank control group(P<0.05);there was no statistically significant difference in the latent periods of rats among the piracetam group,low-dose ligustrazine group,high-dose ligustrazine group,and model group(P>0.05).On the 3rd day of the Morris water maze test,the latent periods of rats in the model group,piracetam group,low-dose ligustrazine group,and high-dose ligustrazine group were significantly higher than those in the blank control group(P<0.05);the latent periods of rats in the piracetam group and high-dose ligustrazine group were significantly lower than those in the model group and low-dose ligustrazine group(P<0.05);there was no statistically significant difference in the latent periods of rats between the low-dose ligustrazine group and the model group(P>0.05).On the 5th day of the Morris water maze test,the latent periods of rats in the model group,piracetam group,low-dose ligustrazine group,and high-dose ligustrazine group were significantly higher than those in the blank control group(P<0.05);the latent periods of rats in the piracetam group and high-dose ligustrazine group were significantly lower than those in the model group and low-dose ligustrazine group(P<0.05);there was no statistically significant difference in the latent periods of rats between the low-dose ligustrazine group and the model group(P>0.05).On the 3rd and 5th days of the Morris water maze test,there was no statistically significant difference in the latent periods of rats between the piracetam group and the high-dose ligustrazine group(P>0.05).The times of rats crossing platform in the model group,piracetam group,low-dose ligustrazine group,and high-dose ligustrazine group were significantly lower than those in the blank control group,and the times of rats crossing platform in the piracetam group and high-dose ligustrazine group were significantly higher than those in the model group and low-dose ligustrazine group(P<0.05);there was no statistically significant difference in the times of rats crossing platform between the low-dose ligustrazine group and the model group(P>0.05);there was no statistically significant difference in the times of rats crossing platform between the piracetam group and the high-dose ligustrazine group(P>0.05).Under the microscope,brown CACNA1E,CALM,and BDNF positive cells could be observed in the hippocampal CA1 region.The expressions of CACNA1E,CALM,and BDNF proteins in the hippocampal CA1 region of rats in the model group,piracetam group,low-dose ligustrazine group,and high-dose ligustrazine group were significantly lower than those in the blank control group,and the expressions of CACNA1E,CALM,and BDNF proteins in the hippocampal CAl region of rats in the piracetam group and high-dose ligustrazine group were significantly higher than those in the model group and low-dose ligustrazine group(P<0.05);there was no statistically significant difference in the expressions of CACNA1E,CALM,and BDNF proteins in the hippocampal CAI region of rats between the low-dose ligustrazine group and the model group(P>0.05);there was no statistically significant difference in the expressions of CACNA1E,CALM,and BDNF proteins in the hippocampal CA1 region of rats between the piracetam group and the high-dose ligustrazine group(P>0.05).The relative expression levels of CACNA1E,CALM,and BDNF proteins and mRNAs in the hippocampal CA1 region of rats in the model group,piracetam group,low-dose ligustrazine group,and high-dose ligustrazine group were significantly lower than those in the blank control group(P<0.05);the relative expression levels of CACNA1E,CALM,and BDNF proteins and mRNAs in the hippocampal CA1 region of rats in the piracetam group and high-dose ligustrazine group were significantly higher than those in the model group and low-dose ligustrazine group(P<0.05);there was no statistically significant difference in the relative expression levels of CACNA1E,CALM,and BDNF proteins and mRNAs in the hippocampal CA1 region of rats between the low-dose ligustrazine group and the model group(P>0.05);there was no statistically significant difference in the relative expression levels of CACNA1E,CALM,and BDNF proteins and mRNAs in the hippocampal CA1 region of rats between the piracetam group and the high-dose ligustrazine group(P>0.05).Conclusion Ligustrazine has significant protective effects on aluminum-induced cognitive impairment in rats and can greatly enhance the learning and memory function of rats.The mechanism may be related to the up-regulation of CANA1E,CALM and BDNF expression in the brain induced by ligustrazine.

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