中国临床药理学杂志2024，Vol.40Issue(13)：1933-1937,5.DOI:10.13699/j.cnki.1001-6821.2024.13.018
银杏叶提取物对脑卒中后抑郁大鼠的影响
Effect of Ginkgo biloba extract in post-stroke depression model rats
摘要
Abstract
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.关键词
银杏叶提取物/脑卒中抑郁/神经炎症/Toll样受体4(TLR4)/核因子-κB(NF-κB)Key words
Ginkgo biloba extract/post-stroke depression/neuroinflammation/Toll like receptor 4(TLR4)/nuclear factor-κB(NF-κB)分类
医药卫生引用本文复制引用
谢思敏,王有琼,莫苗苗,王冬怡,陈海兰,杨斌..银杏叶提取物对脑卒中后抑郁大鼠的影响[J].中国临床药理学杂志,2024,40(13):1933-1937,5.基金项目
广西自然科学基金面上基金资助项目(2023GXNSFAA026239) （2023GXNSFAA026239）
广西自然科学基金青年科学基金资助项目(2018GXNSFBA281120) （2018GXNSFBA281120）
