绞股蓝总苷对慢性脑缺血大鼠海马神经元的保护作用及其机制研究

Protective Effect and Mechanism of Gypenosides on Hippocampus Neurons in Rats with Chronic Cerebral Ischemia

目的探讨绞股蓝总苷对慢性脑缺血大鼠海马神经元的保护作用及可能机制。方法选取50只健康SD大鼠,♂,随机分为假手术组、模型组和绞股蓝高、中、低剂量组,每组10只。通过双侧颈总动脉永久性结扎法,建立慢性脑缺血模型,造模手术后24h,绞股蓝总苷高、中、低剂量组大鼠分别灌胃100,50,25mg·kg^-1的绞股蓝总皂苷,每日1次,连续8周。Morris水迷宫法检测大鼠空间学习记忆力;TUNEL法检测海马部位神经元的凋亡情况;Western blot法检测脑组织GSK-3β和TNF-α蛋白的表达,并检测凋亡相关通路蛋白p38及caspase-3的表达。结果与模型组相比,绞股蓝总苷高、中、低剂量组逃避潜伏期显著缩短(P<0.01),穿台次数明显增多(P<0.05);海马部位神经元凋亡数量明显减少(P<0.01);GSK-3β和TNF-α蛋白的表达显著降低(P<0.01);caspase-3和P38的表达显著降低(P<0.01)。结论绞股蓝总苷通过抑制凋亡通路P38/caspase-3的激活,减少神经元凋亡,从而对神经元发挥保护作用。

OBJECTIVE To explore the protective effect of gypenosides on neurons of hippocampus in rats with chronic cerebral ischemia and its possible mechanism.METHODS Fifty healthy male SD rats were randomly divided into 5 groups: sham operation group,model group,gypenosides high,medium and low dose groups,10 rats in each group.The chronic cerebral ischemia model was established by permanent ligature of bilateral common carotid artery.After 24 h of the operation,rats in gypenosides high,medium and low dose group were fed with 100,50,25 mg·kg^-1 gypenosides saponins respectively,and 1 times·d^-1 for 8 weeks.The Morris water maze method was used to detect the spatial learning and memory of rats;the number of neuron apoptosis in hippocampus was detected by TUNEL;the expression of GSK-3β and TNF-α protein was detected by Western blot,and the expression of apoptosis-related protein P38 and caspase-3 were detected.RESULTS Compared with the model group,the escape latency of gypenosides high,medium and low dose groups was significantly shortened(P<0.01) and the number of passing through the safety platform increased(P<0.05),the number of neuron apoptosis in the hippocampus was significantly decreased(P<0.01),the expression of GSK-3β and TNF-α protein decreased significantly(P<0.01),and the expression of P38 and caspase-3 decreased significantly(P<0.01).CONCLUSION Total glucoside of gypenosides can inhibit the expression of apoptosis- related protein P38 and caspase-3,thus protecting the neurons.