1.Skin pharmacokinetics of inositol nicotinate in heparin sodium inositol nicotinate cream
Yaling CUI ; Qiong WU ; Liangyu MA ; Bei HU ; Dong YAO ; Zihua XU
Journal of Pharmaceutical Practice and Service 2025;43(1):6-9
Objective To establish an HPLC method to determine the concentration of inositol nicotinate(IN) in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t1/2 was (4.555±2.054) h, Tmax was (6±0)h, Cmax was (16.929±2.153)mg/L, AUC0−t was (150.665±16.568) mg·h /L ,AUC0−∞ was (161.074±23.917) mg·h /L, MRT(0−t) was (9.044±0.618)h, MRT(0−∞) was (10.444±1.91) h, CLz/F was (0.19±0.03) L/(h·kg), and Vz/F was (1.19±0.437) L/(h·kg). Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.
2.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
3.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
4.Exploration of Spectrum-effect Relationship of Zhuriheng Dropping Pills Against Macrophage Foaming Based on UPLC-Q-Exactive Orbitrap MS
Qiong ZHAI ; Fangyuan LIANG ; Yuewu WANG ; Ren BU ; Xin DONG ; Jingkun LU ; Peifeng XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):176-186
ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming, the pharmacodynamic components of Zhuriheng dripping pills(ZRH) were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0, 5, 10, 15, 20 times clinical equivalent doses were prepared by a rat everted gut sac(EGS), and the oxidized low density lipoprotein(ox-LDL)-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination, and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids, and partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection(VIP) value>1.0 as contributing components, and Pearson correlation analysis was used to determine the spectral effect relationship, determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α(PPARα), PPARγ, PPARβ, human retinoid X receptor α(RXRA) and nuclear transcription factor-κB(NF-κB) with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was performed to detect the mRNA levels of PPARγ, scavenger receptor A1(SRA1) and adenosine triphosphate-binding cassette transporter A1(ABCA1) in RAW264.7 cells, Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells, and enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination, the ZRH intestinal absorption fluids could significantly reduce macrophage foaming, and intestinal absorption fluids with 15, 20 times clinical equivalent doses had the best effect, the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy, including organic acids, phenylpropanoids, iridoids, flavonoids, bile acids, coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα, PPARγ, PPARβ, RXRA and NF-κB, and the docking energy values were all less than -6.0 kcal·mol-1(1 cal≈4.19 J). The results of validation showed that, compared with the normal group, the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression, a significant decrease in ABCA1 mRNA expression, a significant increase in the level of PPARγ protein expression, and a significant increase in the levels of IL-1β and NF-κB(P<0.01), compared with the model group, the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression(P<0.05, P<0.01), ABCA1 mRNA expression level was significantly up-regulated, the levels of IL-1β and NF-κB were significantly reduced(P<0.01), and PPARγ protein expression level was significantly reduced(P<0.05). ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming, which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors, and can provide a reference for the quality control and clinical application of ZRH.
5.Randomized Controlled Trial and Correlation Analysis of Gandouling Tablet in Treatment of Abnormal Lipid Metabolism of Wilson's Disease with Turbid Phlegm and Blood Stasis
Feng LIANG ; Ting DONG ; Liwei TIAN ; Chenling ZHAO ; Ruixue GUO ; Qiong WANG ; Yuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):121-128
ObjectiveTo investigate the clinical efficacy of Gandouling tablet (GDL) on abnormal lipid metabolism in Wilson
6.Application value of bone cement containing rhbFGF and RHBMP-2 in PKP treatment of osteoporotic lumbar com-pression fracture
Yu-Dong XIA ; Rong ZHANG ; Qiong LIU ; Jia-Ru CHEN
China Journal of Orthopaedics and Traumatology 2024;37(1):15-20
Objective To investigate the effect of bone cement containing recombinant human basic fibroblast growth fac-tor(rhbFGF)and recombinant human bone morphogenetic protein-2(rhBMP-2)in percutaneous kyphoplasty(PKP)treat-ment of osteoporotic vertebral compression fracture(OVCF).Methods A total of 103 OVCF patients who underwent PKP from January 2018 to January 2021 were retrospectively analyzed,including 40 males and 63 females,aged from 61 to 78 years old with an average of(65.72±3.29)years old.The injury mechanism included slipping 33 patients,falling 42 patients,and lifting injury 28 patients.The patients were divided into three groups according to the filling of bone cement.Calcium phosphate con-sisted of 34 patients,aged(65.1±3.3)years old,14 males and 20 females,who were filled with calcium phosphate bone cement.rhBMP-2 consisted of 34 patients,aged(64.8±3.2)years old,12 males and 22 females,who were filled with bone cement con-taining rhBMP-2.And rhbFGF+rhBMP-2 consisted of 35 patients,aged(65.1±3.6)years old,14 males and 21 females,who were filled with bone cement containing rhbFGF and rhBMP-2.Oswestry disability index(ODI),bone mineral density,anteri-or edge loss height,anterior edge compression rate of injured vertebra,visual analog scale(VAS)of pain,and the incidence of refracture were compared between groups.Results All patients were followed for 12 months.Postoperative ODI and VAS score of the three groups decreased(P<0.00l),while bone mineral density increased(P<0.001),anterior edge loss height,anterior edge compression rate of injured vertebra decreased first and then slowly increased(P<0.001).ODI and VAS of group calcium phos-phate after 1 months,6 months,12 months were lower than that of rhBMP-2 and group rhbFGF+rhBMP-2(P<0.05),bone miner-al density after 6 months,12 months was higher than that of rhBMP-2 and group calcium phosphate(P<0.05),and anterior edge loss height,anterior edge compression rate of injured vertebra of group rhbFGF+rhBMP-2 after 6 months and 12 months were lower than that of group rhBMP-2 and group calcium phosphate(P<0.05).There was no statistical difference in the incidence of re-fracture among the three groups(P>0.05).Conclusion Bone cement containing rhbFGF and rhBMP-2 could more effective-ly increase bone mineral density in patients with OVCF,obtain satisfactory clinical and radiological effects after operation,and significantly improve clinical symptoms.
7.Evaluation value of miRNA-21 and miRNA-431 in the development and prognosis of pulmonary tuberculosis
LU Qiong, ; DONG Zhen ; WANG Wanru
China Tropical Medicine 2024;24(2):166-
Objective To evaluate the value of bronchoscopy specimens' microRNA-21 (miRNA-21) and microRNA-431 (miRNA-431) in the development and prognosis of pulmonary tuberculosis. Methods A total of 43 confirmed pulmonary tuberculosis patients admitted to Shaanxi Provincial Tuberculosis Prevention Hospital from May 2022 to July 2023 were included as the study group, and 43 healthy volunteers during the same period were included as the control group. In the study group, the severity of lung lesions was classified as mild in 14 cases, moderate in 19 cases, and severe in 10 cases. According to the prognosis, patients were divided into poor prognosis and good prognosis groups. The miRNA-21 and miRNA-431 levels of patients with different disease severity and prognosis in the study group and the control group were compared, and the factors affecting the development and prognosis of tuberculosis were analyzed by logistic multivariate analysis, and a prediction model for the development and prognosis of tuberculosis was established. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of the model. Results The levels of miRNA-21 and miRNA-431 in the study group were significantly higher than those in the control group, and the difference between groups was statistically significant (P<0.05). In the study group, the levels of miRNA-21 and miRNA-431 were positively correlated with the severity of the disease, and the levels in severe pulmonary tuberculosis patients were significantly higher than those in mild and moderate pulmonary tuberculosis patients, with statistically significant differences between the groups (P<0.05). In the study group, the levels of miRNA-21 and miRNA-431 in patients with pulmonary tuberculosis with poor prognosis were significantly higher than those in patients with pulmonary tuberculosis with good prognosis, with statistically significant differences between the groups (P<0.05). Using miRNA-21 and miRNA-431 expression as independent variables, and the development and prognosis of pulmonary tuberculosis as dependent variables, logistic regression analysis was performed. The results showed that the high expression of miRNA-21 and miRNA-431 were both influential factors for the development and prognosis of pulmonary tuberculosis (P<0.05). The ROC curve analysis showed that the optimal cutoff value of the prediction model was 0.0895, and the area under the curve (AUC) of miRNA-21, miRNA-431 and combined were 0.614 (0.651-0.732), 0.671 (0.686-0.811), and 0.891 (0.787-0.993). Conclusions The high expression levels of miRNA-21 and miRNA-431 in patients with tuberculosis are closely related to the development of the disease and can predict the prognosis of patients with tuberculosis to a certain extent. The comprehensive application value of combined diagnosis is high, and it is recommended to promote clinical use.
8.Prevalence of non-alcoholic fatty liver disease and associated factors in overweight and obese children in Hohhot
YU Qiong, LI Jianying, CAO Puli, LIU Dong, ZHANG Jian, LI Ruifeng
Chinese Journal of School Health 2024;45(5):742-745
Objective:
To explore prevalence and associated factors of nonalcoholic fatty liver disease (NAFLD) in overweight and obese children in Hohhot City, so as to provide the oretical basis for developing health education plans and implementing prevention and treatment of NAFLD in children.
Methods:
A total of 156 overweight and obese children was enrolled from 4 primary schools in Hohhot City using cluster sampling method during 28th Aug. 2022 to 5th Mar. 2023. Height and weight were measured and body mass index was calculated, and fasting blood was taken in the early morning for fasting blood glucose, alanine aminotransferase, aspartate aminotransferase. Single factor analysis was conducted using ttest, χ2 test and Fishers exact probability method, while multivariate analysis was conducted using Logistic regression analysis and subject characteristic curves.
Results:
The differences in age, waist circumference, hip circumference, fasting glucose, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, uric acid, and triglyceride were statistically significant between the nonNAFLD and the NAFLD group (U/t=1 070.0-2 164.0, P<0.05). Significant differences were observed in aspartate aminotransferase (AST) and uric acid levels (AST OR=1.16, 95%CI=1.04-1.28; uric OR=1.01, 95%CI=1.00-1.01, P<0.05). The area under a receiver operating characteristic were 0.737 for aspartate aminotransferase and 0.665 for uric acid, respectively.
Conclusions
The prevalence of NAFLD is high in overweight/obese children in Hohhot, and both elevated aspartate aminotransferase and hyperuricemia could increase the risk of NAFLD in overweight/obese children. Special attention should be paid to the NAFLD in overweight and obese children. It is recommended to reduce both BMI and uric level in the prevention and treatment of NAFLD to achieve better treatment outcomes.
9.Exploration of deferred informed consent in clinical research
Yan WANG ; Xu LI ; Kuikui WEI ; Mengdan LIU ; Qiong WU ; Pingping DONG ; Xiaomei CAO ; Weiqin LI ; Yuxiu LIU
Chinese Medical Ethics 2024;37(2):152-157
Informed consent is an important ethical symbol in clinical research,and researchers have the responsibility to fully inform participants of the research information before conducting clinical research.However,it is difficult to obtain complete informed consent form participants or their guardians within a narrow treatment time period in clinical research conducted in emergency situations.Currently,in addition to traditional general informed consent,there are also reality-accepted informed consent,including exemption of informed consent,broad informed consent,and deferred informed consent.By introducing the origin and development process of deferred informed consent in clinical research,this paper sorted out the current application status of deferred informed consent,proposed the prerequisites for applying deferred informed consent in emergency situations,and explored the issues that need to be noted during the application process of deferred informed consent.It is hoped to provide an ethical defense and ethical procedure for the application of deferred informed consent in clinical research in emergency situations.
10.Effect of Ginkgo biloba extract in post-stroke depression model rats
Si-Min XIE ; You-Qiong WANG ; Miao-Miao MO ; Dong-Yi WANG ; Hai-Lan CHEN ; Bin YANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1933-1937
Objective To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9%NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)%,(91.57±1.03)%,(54.72±7.34)%,(88.35±4.36)%,(63.55±12.73)%and(81.04±4.31)%;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P<0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P<0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P<0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P<0.05,P<0.01),reduced the expression of NF-κB(P<0.01),and reduced the phosphorylation of IKBα(P<0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.


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