丹参酮ⅡA通过增强自噬抑制AGEs诱导内皮细胞凋亡

Tanshinone ⅡA suppresses AGEs-induced endothelial cell apoptosis by enhancing autophagy

目的研究自噬在丹参酮ⅡA抑制晚期糖基化产物(AGEs)诱导内皮细胞凋亡中的作用及相关机制。方法丹参酮ⅡA及AGEs处理内皮细胞,MTT法检测细胞活性,流式细胞术检测细胞凋亡率,Western blot检测相关蛋白量表达。结果与对照组相比,AGEs组和丹参酮ⅡA组自噬相关蛋白LC3-Ⅱ表达增加,SQSTM1/p62表达减少,AGEs+丹参酮ⅡA组LC3-Ⅱ表达进一步增加,SQSTM1/p62表达进一步下降。与对照组相比,AGEs组细胞凋亡率增加,细胞活性下降,与AGEs组相比,AGEs+丹参酮ⅡA组细胞凋亡率下降,细胞活性增加,AGEs+自噬抑制剂3-MA组细胞凋亡率增加,细胞活性下降。丹参酮ⅡA组p-AKT、p-mTOR表达下降,呈时间依赖性。结论丹参酮ⅡA通过增强自噬抑制AGEs诱导的内皮细胞凋亡,这可能与其抑制AKT/mTOR信号通路相关。

Objective To study the effect and mechanism of autophagy in tanshinone Ⅱ A suppressing AGEs-induced endothelial cell apoptosis. Methods Endothelial cells were managed by tanshinone ⅡA and AGEs, MTT was used to detect cell viability, FCM was used to detect cell apoptosis rate, and Western blot was used to detect protein expres- sion. Results Compared with the control group, the expression of autophagy-associated protein LC3- Ⅱ was enhanced in the AGEs group and the tanshinone Ⅱ A group, and the expression of SQSTM1/p62 was reduced. The expression of LC3- Ⅱ was further enhanced in the AGEs＋tanshinone Ⅱ A group, and the expression of SQSTM1/p62 was further re- duced. Compared with the control group, the rate of cell apoptosis was enhanced, and the cell viability was reduced in the AGEs group. Compared with the AGEs group, the rate of cell apoptosis was reduced and the cell viability was en- hanced in the AGEs＋tanshinone Ⅱ A group, and the rate of cell apoptosis was enhanced and the cell viability was re- duced in the AGEs＋autophagy inhibitor 3-MA group. The expressions of p-AKT and p-mTOR were reduced in the tanshinone Ⅱ A group, with time dependence. Conclusion Tanshinone Ⅱ A suppresses AGEs-induced endothelial cell apoptosis by enhancing autophagy, which may he associated with its suppression of AKT/mTOR signal channel.