School of Medicine, Hunan University of Medicine, Huaihua, China.
Department of Pediatrics, First People's Hospital of Huaihua, China.
Adv Clin Exp Med. 2021 Feb;30(2):139-146. doi: 10.17219/acem/130608.
Ischemic stroke, also known as cerebrovascular accident or cerebral stroke, occupies the first place in the world's top 10 causes of death, with high incidence, mortality and disability rates.
To investigate the effect of stilbene glycoside upregulated SIRT3/AMPK expression on neuronal mitochondrial autophagy and neuronal apoptosis in ischemic stroke.
The PC12 cells were cultured without serum to construct an ischemic neuron model. The cells were divided into 6 groups: normal group (untreated cells), model group (ischemic treated cells), TSG group (stilbene glycoside treatment), NC group (SIRT3 and AMPK negative control treatment), si-SIRT3 group (SIRT3 silencing treatment), TSG+si-SIRT3 group (joint treatment), and TSG+si-SIRT3+oe-AMPK group (joint treatment). Cell survival and the expression of related molecules were detected.
Compared with normal group, the model group had significantly decreased cell survival rate, mitochondrial membrane potential, as well as the expression of Bcl-2, LC3II/I, P62, PINK1, Parkin, SIRT3, AMPK, and p-AMPK, while showing significantly increased proportion of apoptosis and the expression of caspase 3 and Bax. Compared with the model group, TSG treatment promoted cell survival rate and mitochondrial autophagy, and inhibited apoptosis, while SIRT3 silencing treatment reduced cell survival rate and mitochondrial autophagy, and increased apoptosis. The SIRT3 silencing could block the inhibitory effect of TSG on the apoptosis of ischemic PC12 cells and promote mitochondrial autophagy, and AMPK overexpression could save the apoptosis of ischemic PC12 cells caused by SIRT3 silencing, and promote mitochondrial autophagy.
By promoting the expression of SIRT3/AMPK, TSG promotes mitochondrial autophagy in ischemic neurons and inhibits their apoptosis.
缺血性脑卒中，又称脑血管意外或脑中风，在全球十大死因中位居榜首，具有发病率、死亡率和致残率高的特点。
探讨二苯乙烯苷上调 SIRT3/AMPK 表达对缺血性脑卒中神经元线粒体自噬及神经元凋亡的影响。
无血清培养 PC12 细胞构建缺血性神经元模型，将细胞分为 6 组：正常组（未处理细胞）、模型组（缺血处理细胞）、TSG 组（二苯乙烯苷处理）、NC 组（SIRT3 和 AMPK 阴性对照处理）、si-SIRT3 组（SIRT3 沉默处理）、TSG+si-SIRT3 组（联合处理）、TSG+si-SIRT3+oe-AMPK 组（联合处理），检测细胞存活率及相关分子表达。
与正常组比较，模型组细胞存活率、线粒体膜电位降低，Bcl-2、LC3II/I、P62、PINK1、Parkin、SIRT3、AMPK、p-AMPK 表达减少，凋亡比例、caspase 3、Bax 表达增加；TSG 处理促进细胞存活率及线粒体自噬，抑制细胞凋亡，SIRT3 沉默处理降低细胞存活率及线粒体自噬，增加细胞凋亡；SIRT3 沉默可阻断 TSG 对缺血性 PC12 细胞凋亡的抑制作用并促进线粒体自噬，AMPK 过表达可挽救 SIRT3 沉默引起的缺血性 PC12 细胞凋亡并促进线粒体自噬。
二苯乙烯苷通过促进 SIRT3/AMPK 表达，促进缺血性神经元线粒体自噬，抑制其凋亡。
