黄芪甲苷肾保护作用机制

Renal protective effects and mechanisms of astragaloside IV

黄芪甲苷IV(AS-IV)是黄芪的主要活性成分之一,AS-IV肾保护作用及机制目前尚未完全阐明。笔者对AS-IV肾保护作用及其分子机制的相关研究进行了综述。AS-IV能上调α3β1整合素及抑制整合素连接酶表达,从而改善高糖诱导的足细胞粘附功能失调;还可通过抗氧化、恢复Bax/Bcl-2表达平衡及抑制Caspase-3激活,从而防治糖尿病肾病足细胞凋亡;可抑制核因子-κB(NF-κB)介导的炎症基因表达,防治缺血性急性肾损伤(AKI);可恢复Bax/Bcl-2表达平衡及抑制Caspase-3和磷酸化p38MAPK过度激活,从而防治缺血性及造影剂肾病和肾小管细胞凋亡;可调节细胞骨架蛋白,减轻补体膜攻击复合物诱导的足细胞损伤,可能被用于治疗膜性肾病。因此,AS-IV可能成为防治肾脏病的新型药物。

Astragaloside IV （AS-IV） is one of the major active components of the astragalus membranaceus （Fisch） Bge. It was reported that AS-IV ameliorated ischemia-reperfusion injury in brain and heart, however, its renal protective effects and mechnisms have not been fully investigated yet. In this paper, we have reviewed the renal protective effects and the molecular mechanisms of AS-IV. AS-IV improved high glucose-induced podocyte adhesion dysfunction, which was partly attributed to ct3~l integrin upregulation and integrin-linked kinase （ILK） inhibition. As a novel antioxidant, AS-IV also prevented glucose-induced podocyte apoptosis partly through restoring the balance of and B cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） expression and inhibiting caspase-3 activation. Moreover, AS-IV prevented ischemic acute kidney injury （AKI） through inhibition of nuclear factor K-light-chain- enhancer of activated B cells （ NF- ~B） mediated inflammatory genes expression. AS- IV also prevented renal dysfunction, tubular injury, and apoptosis in ischemic and contrast-induced AKI models through restoring the balance of Bax/Bcl-2 expression and inhibiting caspase-3 and p38 mitogen-activated protein kinase （MAPK） activation. AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membrane attack complex so that AS-IV might be used to treat membranous nephropathy. Therefore, AS-IV might become a new drug for the prevention and treatment of kidney diseases.