二苯乙烯苷减轻小鼠急性脑缺血再灌注后的氧化应激损伤及其对自噬的影响

Tetrahydroxystilbene glycoside alleviates oxidative stress injury after acute cerebral ischemia-reperfusion in mice and its effect on autophagy

目的 研究小鼠急性脑缺血再灌注损伤(CIRI)后二苯乙烯苷(TSG)对自噬作用的影响及其神经保护作用。方法 雄性昆明种小鼠100只,随机分为假手术组、模型组和TSG低、中、高剂量组(3、6、12 mg/kg)。采用双侧颈总动脉结扎法建立急性脑缺血再灌注模型,缺血2 h再灌注24 h,于缺血和再灌注前尾静脉注射给药各1次。断头取脑检测脑组织含水量,采用试剂盒检测血清中超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量,HE染色检测小鼠脑组织病理变化,蛋白质印迹法检测自噬相关蛋白的表达。结果 与模型组比较,TSG组脑皮层神经元的病理性损伤较轻,神经元数量增加,形态改善,核固缩减轻;TSG中、高剂量组显著降低脑组织含水量及MDA的含量,并可显著升高血清中SOD活性(P <0. 01),TSG高剂量组亦可显著抑制自噬相关基因Atg6 (Beclin1)和微管相关蛋白1轻链3(LC3-Ⅱ/Ⅰ)蛋白的表达(P <0. 05)。结论 TSG对小鼠急性CIRI具有很好的神经保护作用,作用机制可能与抑制CIRI中自噬激活有关。

Objective To investigate the effect of tetrahydroxystilbene glycoside(TSG)on autophagy and its neuroprotective effect after acute cerebral ischemia-reperfusion injury(CIRI)in mice.Methods 100 male swiss mice were randomly divided into sham group,model group and TSG(3 mg/kg)group,TSG(6 mg/kg)group,TSG(12 mg/kg)group.The model of acute cerebral ischemia-reperfusion was established by bilateral common carotid artery ligation.The mice were given ischemia for 2 hours and reperfusion for 24 hours and TSG was injected into the tail vein once before ischemia and reperfusion.The brain water content of brain tissue was detected by decapitation.The activity of superoxide dismutase(SOD)and malondialdehyde(MDA)in serum were detected by kit.The pathological changes of brain tissue were detected by HE staining.The expression levels of autophagy-related proteins were detected by Western blot.Results Compared with the model group,the pathological damages of the cortical neurons in the TSG group were lighter,the number of neurons increased,the morphology improved,and the nuclear pyknosis was relieved.The water content of brain tissue and the content of MDA were reduced by 6 mg/kg and 12 mg/kg dose groups of TSG significantly and the serum SOD activity was significantly increased(P<0.01).The expression levels of autophagy-related gene Atg6(Beclin1)and microtubule-associated protein 1 light chain 3(LC3-Ⅱ/Ⅰ)proteins were also significantly inhibited by 12 mg/kg dose groups of TSG(P<0.05).Conclusion TSG has a good neuroprotective effect on acute cerebral ischemia-reperfusion injury in mice.Its mechanism may be related to the inhibition of autophagy activation in cerebral ischemia-reperfusion injury.