三七总皂苷抑制星形胶质细胞活化改善脂多糖导致的小鼠抑郁样行为

Panax notoginseng saponin relieves LPS-induced depression-like behavior by inhibiting activation of astrocytes in mice

目的 :观察三七总皂苷(PNS)对脂多糖(LPS)诱导的小鼠抑郁样行为以及海马星形胶质细胞(AST)活化的影响。方法 :将小鼠随机分为生理盐水(NS)组、LPS组、PNS+LPS组。利用喷糖实验、糖水偏好实验及强迫游泳实验检测小鼠抑郁样行为,免疫组织化学显色观察胶质原纤维酸性蛋白(GFAP)的表达变化,免疫印迹检测海马GFAP、乙醛脱氢酶1蛋白家族L1(ALDH1L1)的表达变化,荧光定量PCR检测海马GFAP和肿瘤坏死因子-α(TNF-α)mRNA的表达。结果 :与NS组相比,LPS组舔糖潜伏期延长、糖水偏好百分比下降、强迫游泳不动时间增加,PNS预处理可逆转上述抑郁样行为;与NS组相比,LPS组海马GFAP阳性细胞数目增加,GFAP及ALDH1L1蛋白表达上调,GFAP及TNF-αmRNA表达上调,PNS预处理均可减少GFAP、ALDH1L1及TNF-α的表达;结论 :三七总皂苷可能通过抑制星形胶质细胞活化,改善脂多糖导致的小鼠抑郁样行为。

Objective:To explore the effect of panax notoginseng saponins(PNS)on lipopolysaccharide(LPS)-induced depression-like behavior and activation of astrocytes(AST)in mice.Methods:Male Kunming mice were randomly assigned to NS group,LPS group,and PNS+LPS group.Splash test,Sucrose preference test(SCPT)and force swimming test(FST)was used to observe the depression-like behavior.Expression of astrocyte marker GFAP and ALDH1L1 in the hippocampus was determined by immunohistochemistry and Western blotting.RT-qPCR was used to investigate the mRNA expression of GFAP and TNF-α.Results:LPS led to prolonged latency in the Splash test,reduced sucrose preference,and increased immobility time in forced swimming test,while PNS evidently reversed the LPS-induced depression-like behavior.Immunohistochemistry result showed that LPS led to significantly increased number of GFAP positive cells in the hippocampus.Western blotting results showed that LPS led to significantly increased expression of GFAP and ALDH1L1 in the hippocampus.PCR results showed that mice in LPS group had increased mRNA expression of GFAP and TNF-αin the hippocampus,while PNS attenuated the expression of abovementioned indexes.Conclusion:PNS can relieve LPS-induced depression-like behavior in mice by inhibiting activation of astrocytes in the hippocampus.