竹节参总皂苷调节大鼠海马区自噬减轻脑缺血再灌注损伤

Total Rhizome Panacis japonica saponins ameliorate cerebral ischemia reperfusion injury via regulating autophagy in rats’hippocampus

目的探讨竹节参总皂苷对脑缺血再灌注损伤大鼠海马组织中自噬的影响。方法 40只SD雄性大鼠随机分为假手术组、模型组、竹节参总皂苷低剂量组(50 mg/kg)、竹节参总皂苷高剂量组(100 mg/kg)。提前连续给药7 d。末次给药30 min后,采用线栓法制备大脑中动脉闭塞模型使大鼠缺血1.5 h,再灌注24 h后进行神经功能评分。TTC染色检测脑梗死范围百分比,电镜观察自噬小体,Western blot检测海马组织中微管相关蛋白1轻链3(LC3)、自噬底物蛋白p62的蛋白表达。结果与假手术组相比,模型组大鼠神经功能评分和脑梗死范围百分比增加(P<0.01),自噬小体增多,LC3-Ⅱ/LC3-Ⅰ增加(P<0.01),p62表达下调(P<0.01)。与模型组比较,竹节参各组大鼠的神经功能损伤明显改善,脑梗死范围百分比减小(P<0.01),自噬小体减少,LC3-Ⅱ/LC3-Ⅰ降低(P<0.01),p62表达上调(P<0.01)。结论竹节参总皂苷可能通过抑制自噬的过度激活,从而减轻脑缺血再灌注损伤的发生。

AIM To explore the effect of total Rhizome Panacis japonica saponins(tRPJSs)on autophagy in rats’hippocampal injured by cerebral ischemia⁃reperfusion(CIR).METHODS Forty male Sprague⁃Dawley rats were randomly divided into 4 groups:sham group,model group,low⁃dose tRPJSs group(50 mg/kg),high⁃dose tRPJSs group(100 mg/kg).For the rats pretreated with either tRPJSs or saline solution consecutively for 7 days,30 min after the last administration,they were built middle cerebral artery occlusion models by thread⁃occlusion method for 1.5 h of ischemia and 24 h of reperfusion.And then the rats had the neurological deficit scores assessment,the infarct volume calculation by TTC staining,the autophagosome observation by electron microscopy,and the expression levels of microtubule⁃associated protein 1 light chain 3(LC3)and p62 detection by Western Blot.RESULTS Compared with the sham group,the model group were observed with increased neurological deficit scores and percentage of cerebral infarct(P<0.01),increased number of autophagosomes and increased rate of LC3⁃Ⅱ/LC3⁃Ⅰ(P<0.01),and markedly down⁃regulated expression of p62(P<0.01).Compared with the model group,tRPJSs groups shared markedly ameliorated neurological deficits,reduced percentage of cerebral infarct(P<0.01),reduced autophagosomes number,decreased rate of LC3⁃Ⅱ/LC3⁃Ⅰ(P<0.01),and markedly up⁃regulated expression of p62(P<0.01).CONCLUSION tRPJSs may alleviate cerebral ischemia⁃reperfusion injury via suppressing the over⁃activation of autophagy.