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目的探讨缺氧诱导因子2α(HIF-2α)在缺氧诱导LO2肝细胞凋亡中的作用及其机制。方法构建HIF-2α特异性的沉默干扰RNA(siRNA)并转染LO2细胞,分别在常氧及缺氧条件下培养细胞,采用流式细胞术检测细胞凋亡,Western blot法检测内质网应激及细胞凋亡相关蛋白的表达。结果与常氧条件相比,缺氧处理后HIF-2α表达、细胞凋亡、内质网应激与凋亡相关蛋白表达均明显增加,而siRNA能有效抑制上述指标的增加过程。结论缺氧条件下HIF-2α通过内质网应激途径引发LO2细胞凋亡,可能是缺氧性肝脏疾病治疗的一个潜在靶点。
Objective To investigate the role of hypoxia inducible factor 2α (HIF-2α) in hepatocyte apoptosis induced by hypoxia in LO2 and its mechanism. Methods HIF-2α specific silencing RNA (siRNA) was constructed and transfected into LO2 cells. The cells were cultured under normoxia and hypoxia respectively. The apoptosis of cells was detected by flow cytometry. The endoplasmic reticulum Stimulate the expression of apoptosis-related proteins. Results Compared with normoxic condition, the expression of HIF-2α, apoptosis, endoplasmic reticulum stress and apoptosis-related protein expression were significantly increased after hypoxia treatment, and siRNA could effectively inhibit the increase of the above parameters. Conclusions Hypoxia induces apoptosis of LO2 cells through the endoplasmic reticulum stress pathway, which may be a potential target for the treatment of hypoxic liver disease.