摘要
目的:探讨丹参酮ⅡA对阿霉素(又称多柔比星)所致大鼠H9c2心肌细胞损伤的影响和机制。方法:以H9c2细胞为研究对象,在有或无AMPK抑制剂dorsomorphin处理下,采用丹参酮ⅡA和(或)阿霉素处理H9c2细胞,应用CCK-8法测定细胞活力,LDH法测定细胞损伤情况,免疫荧光实验分析细胞自噬情况,Western blot检测细胞AMPK的活化情况。结果:与对照组相比,阿霉素处理后H9c2细胞的活力减弱,LDH释放增多,自噬增加,AMPK的活化受抑制(P<0.05);与阿霉素组相比,加用丹参酮ⅡA联合处理能部分恢复H9c2细胞的活力,减少LDH释放,进一步增加自噬,促进AMPK活化(P<0.05);AMPK抑制剂dorsomorphin处理后,丹参酮ⅡA恢复H9c2细胞活力、减少LDH释放和促进自噬的作用减弱(P<0.05)。结论:丹参酮ⅡA能减轻阿霉素所致H9c2心肌细胞的损伤,其机制可能与激活AMPK介导的自噬有关。本研究为临床上应用丹参酮ⅡA防治阿霉素心肌损伤提供实验基础和理论依据。
AIM: To investigate the effect of tanshinone ⅡA on doxorubicin-induced rat H9c2 cardiomyocyte injury. METHODS: The H9c2 cardiomyocytes were treated with tanshinone ⅡA and/or doxorubicin with or without AMPK inhibitor dorsomorphin. The cell viability was measured by CCK-8 assay, the LDH release was examined for evaluating the cell injury, autophagy was analyzed by immunofluorescence staining, and AMPK activation was determined by Western blot. RESULTS: Compared with control group, the viability of H9c2 cells was decreased, the release of LDH was increased, the autophagy degree was increased, and AMPK activation was inhibited after treatment with doxorubicin(P<0.05). Compared with doxorubicin group, the treatment with tanshinone ⅡA restored the cell viability, reduced the release of LDH, further increased autophagy degree, and activated AMPK in the H9c2 cells(P<0.05). AMPK inhibitor dorsomorphin attenuated the abilities of tanshinone ⅡA to restore the cell viability, reduce the release of LDH, and increase autophagy degree in the H9c2 cells(P<0.05). CONCLUSION: Tanshinone ⅡA attenuates doxorubicin-induced injury in H9c2 cardiomyocytes, and its mechanism might be related to AMPK-mediated autophagy, which provides experimental and theoretical basis for the clinical application of tanshinone ⅡA in the prevention and treatment of doxorubicin-induced cardiomyocyte injury.
作者
王朝华
徐勤
肖慧琼
袁李礼
WANG Zhao-hua;XU Qin;XIAO Hui-qiong;YUAN Li-li(Department of Cardiology,Brain Hospital of Hunan Province,Changsha 410007,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2019年第3期406-410,共5页
Chinese Journal of Pathophysiology
基金
湖南省自然科学基金资助项目(No.2018JJ3285)
湖南省卫生计生委科研计划课题项目(No.B20180079)
作者简介
通讯作者:袁李礼,Tel:0731-85232242,E-mail:shushu622@qq.com.
