Tang Biao, She Xu, Deng Chang-Qing
Department of Physiology, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China.
Exp Ther Med. 2021 Oct;22(4):1123. doi: 10.3892/etm.2021.10557. Epub 2021 Aug 4.
Pyroptosis and necroptosis are closely associated with the mechanism underlying cerebral ischemia-reperfusion (I/R) injury. The combination of astragaloside IV (AST IV) and saponins (PNS) has remarkable effects on the alleviation of cerebral I/R damage. However, whether inhibition of pyroptosis and necroptosis is the mechanism underlying the beneficial effects of this drug combination on cerebral I/R injury remains unclear. To explore the effects and mechanisms of drug treatment, middle cerebral artery occlusion was performed to induce I/R injury in rats, which was verified based on neurological deficit score (NDS), infarct volume and H&E staining. Activation of pyroptosis and necroptosis was detected by western blot analysis of associated proteins. The results of the present study demonstrated that treatment with AST IV and PNS, either alone or in combination, significantly reduced the NDS, cerebral infarct volume and cell injury rate in the cerebral cortex of rats. The treatments also improved pathological injury to the cerebral cortex and reduced the levels of proteins associated with pyroptosis and necroptosis. These effects were stronger in the combination drug group compared with groups treated with a single drug alone. The findings of the present study suggested that the combination of AST IV and PNS exhibited stronger neuroprotective effects in I/R injury than either drug alone, and that the underlying mechanism was associated with inhibition of pyroptosis and necroptosis.
细胞焦亡和坏死性凋亡与脑缺血再灌注（I/R）损伤的潜在机制密切相关。黄芪甲苷（AST IV）和三七总皂苷（PNS）联合使用对减轻脑I/R损伤具有显著效果。然而，抑制细胞焦亡和坏死性凋亡是否是这种药物组合对脑I/R损伤产生有益作用的机制仍不清楚。为了探究药物治疗的效果和机制，采用大脑中动脉闭塞法诱导大鼠I/R损伤，并通过神经功能缺损评分（NDS）、梗死体积和苏木精-伊红（H&E）染色进行验证。通过对相关蛋白的蛋白质印迹分析检测细胞焦亡和坏死性凋亡的激活情况。本研究结果表明，单独或联合使用AST IV和PNS治疗均能显著降低大鼠的NDS、脑梗死体积以及大脑皮质的细胞损伤率。这些治疗还改善了大脑皮质的病理损伤，并降低了与细胞焦亡和坏死性凋亡相关的蛋白水平。与单独使用单一药物治疗的组相比，联合用药组的这些效果更强。本研究结果表明，AST IV和PNS联合使用在I/R损伤中比单独使用任何一种药物都具有更强的神经保护作用，其潜在机制与抑制细胞焦亡和坏死性凋亡有关。
