| 张 铮,杨 超,靳志涛,蒋 伟,赵 力,杨军珂,丁力平,王承竹,柳彦君,孙志敏,胡桃红.mTOR信号通路诱导的自噬在心肌细胞缺氧损伤中的作用研究[J].,2017,17(9):1619-1622 |
| mTOR信号通路诱导的自噬在心肌细胞缺氧损伤中的作用研究 |
| The Effect of mTOR induced Autophagy on the Apoptosis of Cardiomyocytes induced by Hypoxia |
| 投稿时间：2016-09-23 修订日期：2016-10-13 |
| DOI：10.13241/j.cnki.pmb.2017.09.005 |
| 中文关键词: mTOR 心肌细胞 缺氧/去血清损伤 自噬 凋亡 |
| 英文关键词: mTOR Cardiomyocytes Hypoxia/serum deprivation injury Autophagy Apoptosis |
| 基金项目:国家自然科学基金青年科学基金项目（81400274，31600681，31440039） |
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| 中文摘要: |
| 摘要 目的：探讨自噬在心肌细胞缺氧损伤中的作用及分子机制。方法：体外分离培养乳鼠心肌细胞，体外建立缺氧/去血清（H/SD）模型以模拟在体的缺血环境。分别给予自噬抑制剂3-甲基腺嘌呤 (3MA, 5 mM)和mTOR抑制剂雷帕霉素(1.0 μg/L)调节心肌细胞自噬水平。分别采用TUNEL染色检测心肌细胞凋亡，Western blot方法检测心肌细胞蛋白表达水平。结果：H/SD损伤可以显著诱导心肌细胞自噬水平(P<0.05)，并且细胞自噬水平可以被3-MA及雷帕霉素调节。同时，H/SD可以显著增加心肌细胞凋亡(P<0.05)，而给予3-MA抑制自噬水平可以减少细胞凋亡(P<0.05)。相反，雷帕霉素增加自噬同样可以加重缺氧导致的心肌细胞凋亡(P<0.05)。H/SD损伤过程中，心肌细胞mTOR信号通路被激活，而自噬抑制剂3-MA可以显著提高缺氧条件下心肌细胞中p-mTOR(Ser2448)的表达水平（P<0.05），并增加mTOR下游分子p-p70S6k（P<0.05）和p-S6（P<0.05）的表达。结论：mTOR信号通路诱导的细胞自噬可能参与了缺氧损伤诱导的心肌细胞凋亡。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the potential role of autophagy on apoptosis in cardiomyocytes(CMs) induced by hypoxic in- jury. Methods: CMs were cultured in normal or hypoxia/serum deprivation (H/SD) medium for 24 h. The autophagy state was regulated by 3-Methyladenine (3MA) and rapamycin administration. Furthermore, TUNEL assay was performed to determine apoptosis in CMs. Moreover, Western blot assay was performed to assess the expressions of signaling proteins. Results: Hypoxic stress increased autophagy and apoptosis in CMs. Meanwhile, hypoxia increased the activation of mTOR signaling. Moreover, the apoptosis in CMs induced by hy- poxia injury was abolished by 3-MA, whereas was aggravated by rapamycin. Conclusion: Our data provide evidence that mTOR signal- ing induced autophagy may play an essential role in the apoptosis of CMs induced by hypoxic injury. |
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