针刺调控自噬保护脑缺血再灌注损伤的研究进展

Progress of researches on acupuncture treatment of cerebral ischemia-reperfusion injury by regulating autophagy in the ischemic cerebral tissue

自噬是机体的一种自我保护机制,在缺血、缺氧等应激状态下对维持细胞存活和内环境的稳定起到重要作用。但是,过度的自噬可启动细胞的自噬性细胞凋亡。研究发现,针刺不仅能直接调控自噬体的数量,调控自噬相关蛋白微管相关蛋白1轻链3、B淋巴细胞瘤基因2同源结构域蛋白和自噬底物蛋白p62的表达,还可以通过调控Ⅲ型磷脂酰肌醇3激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白(mTOR)及腺苷酸活化蛋白激酶-mTOR-UNC51样激酶1相关信号通路来抑制或激活自噬,从而改善脑缺血再灌注损伤(CIRI)。通过总结近年来针刺调控自噬防治CIRI的研究,为临床推广运用针刺治疗缺血性脑卒中提供实验依据。

Excessive autophagy is one of the crucial factors of cerebral ischemia-reperfusion injury(CIRI),which has been demonstrated to be one of the targets for acupuncture treatment of ischemic stroke.In the present paper,we make a review about the development of acupuncture intervention induced improvement of CIRI(such as reducing the infarction area,improving learning-memory ability and motor function)by regulating autophagy in animal studies.Outcomes showed that acupuncture intervention can function in 1)inhibiting CIRI-induced increase of the number of lysosomes and autophagic lysosomes,and relieving structural injury of mitochondria,and reducing the number of autophagosome in the central region of the ischemic cerebral cortex tissue;2)down-regulating the expression of microtubule-associated proteinⅡlight chain 3(LC3Ⅱ)and the ratio of LC3-Ⅱ/LC3-Ⅰin the ischemic cerebral region,and 3)regulating the expression of Beclin 1(autophagy-related gene),promoting the expression of P62(autophagy-related adaptor protein).In addition,acupuncture can also regulate phosphoinositide 3 kinase(PI3 K)-protein kinase B(AKT)-mammalian target of rapamycin complex 1(mTOR)signaling at different time-points(down-regulation at the early stage and up-regulation at the later stage),and activating AMP-activated protein kinase(AMPK)-mTOR-UNC51-like kinase-1 signaling to relieve cerebral ischemic injury.These results reveal some mechanisms of acupuncture therapy underlying improvement of CIRI and provide experimental basis for clinical application of acupuncture therapy in the treatment of ischemic stroke.