五味子醇甲通过调控自噬流减轻大鼠脑缺血再灌注损伤

目的:探究五味子醇甲(Sch A)减轻大鼠脑缺血再灌注损伤的作用及其潜在机制.方法:成年雄性SD大鼠随机分为假手术组(sham组)、模型组[大脑中动脉闭塞(MCAO)组]及Sch A低、中、高剂量治疗组,每组6只.制备大鼠左侧MCAO模型,90 min后再灌注,治疗组Sch A的剂量分别为40、80和160μg·kg?...

Schisandrin A attenuates cerebral ischemia-reperfusion injury in rats by regulating autophagic flux

AIM:To investigate the protective effect of schisandrin A(Sch A)on the brain of rats with cerebral ischemia-reperfusion injury and its potential mechanism.METHODS:Male SD rats were subjected to left middle cerebral artery occlusion(MCAO)for 90 min before reperfusion.The rats were divided into sham operation group(sham group),model group(MCAO group),low-dose Sch A group,medium-dose Sch A group,and high-dose Sch A group(n=6 in each group).The low,medium and high doses of Sch A were 40,80 and 160μg·kg^?1·d^?1,respectively.The modified neurological severity scores(mNSS)were evaluated after 7 d,and the volume of cerebral infarction was detected by TTC staining.The autophagic flux was assessed by Western blot detection of the expression levels of autophagy-associated proteins P62,LAMP1,cathepsin B and ubiquitin in brain ischemic penumbra neurons.Immunofluorescence double labeling was used to detect the induction of autophagy in the neurons of cerebral ischemic penumbra by Sch A.RESULTS:Compared with MCAO group,the mNSS and cerebral infarction volume of the MCAO rats treated with Sch A were decreased in a dose-dependent manner,with significant difference in high-dose Sch A group(P<0.05).Compared with sham group,the protein expression of cathepsin B in MCAO group was decreased,and the protein expression of P62 and ubiquitin was increased(P<0.05).Compared with MCAO group,the protein expression of cathepsin B was increased significantly after Sch A treatment,while the protein expression of P62 and ubiquitin was decreased,also with significant difference in high-dose Sch A group(P<0.05).The difference of LAMP1 level in each group was not statistically significant(P>0.05).Moreover,the immunofluorescence results showed that compared with MCAO group,the proportion of LC3-Ⅱ positive neurons in the cerebral ischemic penumbra of the rats in Sch A groups was increased,and the increase was significant in high-dose Sch A group(P<0.01).CONCLUSION:Sch A may induce neuronal autophagy in the cerebral ischemic penumbra of SD rats and reverse the expression levels of neuronal autophagy-related proteins cathepsin B,P62 and ubiquitin to protect against cerebral ischemia-reperfusion injury.