1.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
2.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
3.Effect of Shufeng Jiedu Capsules on Relieving Influenza Virus Pneumonia by Suppressing TLR/NF-κB Pathway in Respiratory Epithelial Cells
Zihan GENG ; Lei BAO ; Shan CAO ; Qiang ZHU ; Jun PAN ; Shuran LI ; Ronghua ZHAO ; Jing SUN ; Yanyan BAO ; Shaoqiu MU ; Xiaolan CUI ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):61-68
ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules (SFJD) in alleviating influenza A (H1N1) virus pneumonia and focus on its effect on Toll-like receptor (TLR) signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 (PR8) strain of influenza A virus. Mice were randomly divided into a normal group, a PR8 infection (PR8) group, and an SFJD group (8.4 g·kg-1), with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg-1 daily, while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography (Micro-CT) was performed on day 5, and the mice were dissected to collect their lungs, after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR, tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) proteins in epithelial cell adhesion molecule (EpCAM)-positive cells, and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry, and Western blot was used to detect the expression of TLR, MyD88, TRAF6, Toll-interleukin receptor domain-containing adaptor inducing interferon-β (TRIF), inhibitor of κB kinase α (IKKα), and nuclear factor-κB (NF-κB) in the sorted epithelial cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in lung tissue. ResultsAt the transcriptional level, SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells, downregulating multiple TLR signaling pathway-related genes (P<0.01). At the protein level, SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 (P<0.05), the expression levels of TLR2, TLR3, TLR4, TRIF, TRAF6, IKKα, and NF-κB in epithelial cells(P<0.05, P<0.01), as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue (P<0.01). ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.
4.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
5.Measles virus antibody levels in cord blood of 1 058 newborns in Ankang city of Shaanxi Province
Chunge WAN ; Xiaoqiang DAI ; Yanqi LUO ; Lin XIANG ; Lei CHEN ; Yanyan FU
Chinese Journal of Microbiology and Immunology 2024;44(9):809-813
Objective:To analyze the levels of antibody to measles virus in cord blood of newborns in Ankang city, and provide reference for the development of measles prevention and control measures and strategies.Methods:From January to December, 2023, 1 058 pregnant women from 10 county-level general hospitals in Ankang city were recruited in this study. Neonatal umbilical cord blood samples were collected for detecting IgG antibody against measles with ELISA. SPSS 21.0 software was used to analyze the positive rate of antibody to measles virus and the influencing factors.Results:The overall positive rate of IgG antibody to measles virus was 89.22% (944/1 058), and the geometric mean concentration (GMC) was 570.26 mlU/ml. The positive rates of IgG antibody against measles virus in umbilical cord blood of neonates born to women aged ≤20, 21-25, 26-30, 31-35, and ≥36 years old were 91.07% (51/56), 90.27% (232/257), 89.54% (351/392), 88.12% (230/261), and 86.96% (80/92), respectively (χ 2=1.355, P=0.852). Multivariate logistic regression analysis showed that the positive rate of IgG antibody against measles virus in umbilical cord blood samples was higher in neonates with gestational age ≥37 weeks than in those with gestational age <37 weeks [OR (95%CI): 0.403 (0.262-0.622)]. Besides, the positive rate was also higher in newborns with a birth weight of 3.0-3.5 kg than in those with birth weight <3 kg or ≥3.5 kg [OR (95%CI): 0.868 (0.462-1.629), 1.765(1.087-2.865)]. Conclusions:The positive rate and the GMC of IgG antibody to measles virus in neonatal umbilical cord blood decrease with maternal age. It is recommended that women of childbearing age should receive supplementary immunization with measles-containing vaccine before pregnancy.
6.Characterization of muscle synergy during sitting and standing in older adults with hallux valgus
Yanyan LIU ; Lei QIAN ; Ruiping LIU ; Jun OUYANG ; Gang LIU
The Journal of Practical Medicine 2024;40(10):1376-1381
Objective To analyze changes in neuromuscular control during sit-to-stand(STS)in older adults with hallux valgus(HV)through muscle synergy,and thus to explore the effect of falls in older adults with HV.Methods Four groups of subjects were included in this study,13 young controls(YC);12 young HVgroup(HVY);14 healthy elderly controls(EC);and 15 elderly HV group(HVE).All subjects completed the STS maneuver in an armless chair,and EMG data were integrated using non-negative matrix factorization to compare muscle synergies in the YC,HVY,EC,and HVE groups;plantar pressures(COP),ground reaction forces(GRF),and fall scores(FES-I)were collected.Results Compared with YC group,HVY,EC,and HVE groups had lower relative activation amplitude of abductor hallucis and lateral gastrocnemius in STS preparation phase;meanwhile,EC and HVE groups needed more muscle activation to maintain stability of trunk and foot-ankle joints in STS stabi-lization phase;and HVE group needed more co-contractions of thigh muscles to maintain stability of the knee joint.The COP,FES-I of HVE group was higher than that of the other groups(P<0.05).Conclusion In STS,healthy older adults and older adults with HV required more muscle activation to maintain trunk and ankle stability;older adults with HV required more co-contraction of the thigh muscles to maintain knee stability;in addition to this,older adults with HV were more prone to falls.
7.Establishment and Analysis of the Method for Determining Silicone Oil Content on the Surface of Rubber Closures
Xiaocong PU ; Kun REN ; Yanyan GUO ; Huangjing LIN ; Daiguo ZHAO ; Lei CHEN
Herald of Medicine 2024;43(11):1769-1773
Objective To establish a method for determining the amount of silicone oil on the surface of rubber closures,which is one of the packaging material standards in the Pharmacopoeia of the People's Republic of China.Methods The development process of the method for determining silicone oil content on the surface of rubber closures was described,taking the infrared transmission mode as example.Through method validation,the scientific and rational aspects of the method were examined.Key points of the determination method were analyzed,including the selection of quantitative peaks,selection of measurement solvent,selection of extraction solvent and conditions,selection of instrument measurement methods,selection of liquid cell windows for infrared transmission mode,selection of quantification methods,and selection of dimethyl silicone oil reference standards.Results The infrared spectroscopy mode was chosen to determine the amount of polydimethylsiloxane on the surface of rubber closures based on the peak height of the Si-CH3 bond vibration absorption at 1 260 cm-1.Cyclohexane was used as the measurement solvent.The same concentration of polydimethylsiloxane reference solution was measured using both infrared transmission mode and attenuated total reflection mode,and quantification was performed based on peak height.The results from the two measurement modes were essentially the same.The linear range of polydimethylsiloxane was about 0.3-10.0 mg·mL-1,and its correlation coefficient was 0.999 8.The average recovery of the method was 102.3%-105.6%.The LOD of polydimethylsiloxane was 0.1 mg·mL-1.The silicone oil measurement results of seven batches for rubber closures were consistent with the silicone oil amounts provided by the manufacturer.Conclusion Enterprises can choose either the infrared transmission mode or the attenuated total reflection mode to measure the amount of polydimethylsiloxane on the surface of rubber closures based on their actual conditions.
8.Analysis of pathological differences in lupus nephritis between the Li and Han ethnic groups in Hainan
Wenjuan LEI ; Ju CHEN ; Yanyan FENG ; Jun ZHOU
Journal of Chinese Physician 2024;26(5):712-716
Objective:To explore the differences in renal pathological characteristics between Li and Han patients with lupus nephritis (LN) in Hainan region.Methods:A retrospective analysis was conducted on the renal pathological data of 135 patients with systemic lupus erythematosus (SLE) who underwent renal biopsy in the Department of Nephrology and Rheumatology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from January 2013 to December 2023. They were divided into Li ( n=22) and Han ( n=113) patients according to their ethnicity. The SLE disease activity index (SLEDAI-2000), renal pathological classification, glomerulosclerosis, and tubulointerstitial lesions of LN patients from different ethnicities were analyzed. Results:During the follow-up period, there was no statistically significant difference in the incidence rate of end-stage renal disease in LN patients between Li nationality and Han nationality (13.6% vs 7.9%, P=0.656). The SLEDAI-2000 score of Li ethnic LN patients was mainly mild and moderate activity, while Han ethnic LN patients were mainly moderate and severe activity. There was no statistically significant difference in SLEDAI-2000 between the two groups ( P=0.577). The pathological subtypes of LN patients in both Li and Han ethnic groups are mainly Ⅳ/Ⅳ+ Ⅴ. There was no statistically significant difference between the two groups in different pathological subtypes of Ⅰ, Ⅱ, Ⅲ/Ⅲ+ Ⅴ, Ⅳ/Ⅳ+ Ⅴ, and Ⅴ (all P>0.05). There was no statistically significant difference in AI and CI between the two groups (all P>0.05). There was no statistically significant difference in the proportion of glomerulosclerosis between Li and Han LN patients ( P>0.05). However, the acute and chronic renal tubulointerstitial lesions in Li ethnic LN patients are more severe than those in Han ethnic group ( P=0.008 and P=0.038). Conclusions:The incidence rate of end-stage renal disease in LN patients of Li nationality is higher than that in Han nationality. The acute and chronic renal tubular and interstitial lesions in LN patients of Li nationality are more serious than those in Han nationality.
9.Qualitative and Quantitative Analysis of Chest CT Features of Anti-MDA5 Antibody Positive Dermatomyositis
Lei WANG ; Yanyan XU ; Zhenguo HUANG ; Yanhong REN ; Xiaoming SHU ; Min LIU
Chinese Journal of Medical Imaging 2024;32(6):559-563,571
Purpose To observe the CT imaging features of dermatomyosistis patients with anti-melanoma differentiation related genes 5(MDA-5),and to analyze the relationship between CT imaging indicators and short-term prognosis of patients.Materials and Methods Sixty-seven MDA-5-positive dermatomyosistis patients admitted to China-Japan Friendship Hospital from January 2017 to December 2018 were retrospectively included.Prognosis of included patients in one year were followed-up.Analysis of the relationship between chest CT imaging and short-term poor prognosis.Results Among 67 patients,nine patients died in one year.There was a statistically significant difference between the two groups(the death group and the survivor group)in the interstitial lung disease(ILD)imaging types(χ2=0.198,P=0.025)and pulmonary/aortic diameter ratios(U=103.0,P=0.004).CT imaging of dermatomyosistis-ILD with anti-MDA5 antibody positive patients showed organizing pneumonia.Mortality of diffuse alveolar damage type was significantly higher than that of other types.Logistic regression analysis showed that pulmonary/aortic diameter ratio(OR:4.208,P=0.002)was a strong independent risk factor for the death of patients with anti-MDA5 antibody.Conclusion Most patients with anti-MDA5 antibody positive dermatomyositis show ILD,with the main feature of organic pneumonia.Patients with poor prognosis within 1 year have different types of ILD,while the pulmonary/aortic diameter ratio is a strong independent risk factor for the death of dermatomyosistis-ILD with anti-MDA5 antibody positive patients.
10.Improvement of Depression-like Behavior of Depression Model Mice by Sinisan via Regulating GSK-3β/A20/C/EBPβ to Inhibit Activation of Microglia
Hongyun CHEN ; Dongying YANG ; Huiqing LIAO ; Yanyan ZENG ; Linke PAN ; Shasha BAI ; Di DENG ; Yafei SHI ; Rong ZHANG ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):16-23
ObjectiveTo investigate the antidepressant effect of Sinisan (SNS) by regulating glycogen aynthase kinase-3β (GSK-3β)/tumor necrosis factor alpha-induced protein 3(A20)/CCAAT enhancer binding protein β(C/EBPβ) to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group, model group, fluoxetine group (5.0 mg·kg-1), low-dose Sinisan group (4.9 g·kg-1), medium-dose Sinisan group (9.8 g·kg-1), and high-dose Sinisan group (19.6 g·kg-1), with 12 mice in each group. After one week of adaptive feeding, chronic unpredictable mild stress (CUMS) was performed to establish the depression model. In the fifth week, drug treatment was conducted for four weeks. In the ninth week, behavioral tests were performed, including sucrose preference test (SPT), open field test (OPT), elevated plus maze (EPM) test, and forced swimming test (FST). Western blot was used to detect the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide synthase (iNOS), GSK-3β, A20, and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68) in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS, compared with the normal group, the mice in the model group had a significantly reduced sucrose preference rate (P<0.01), and the activity in the central area of the OPT was significantly reduced (P<0.01). The activity in the open arm area of the EPM test was significantly reduced (P<0.05), and the immobility time of FST was increased (P<0.01). The expression levels of inflammatory proteins IL-1β, IL-6, and iNOS were increased (P<0.01), and the fluorescence co-localization index of Iba1 and CD68 was increased (P<0.05). The protein expression levels of GSK-3β and C/EBPβ were significantly increased (P<0.05, P<0.01). After four weeks of SNS intervention, compared with the model group, the mice in the SNS group had significantly increased sucrose preference rate (P<0.01), significantly increased activities in the central area and the open arm area in the OPT and the EPM test (P<0.05), and significantly reduced immobility time in the FST (P< 0.01). The protein expression levels of IL-1β, IL-6, and iNOS were significantly decreased (P<0.05), and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group (P<0.05). The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased (P<0.01), and that of A20 was significantly increased (P<0.01). ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

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