熊去氧胆酸对阿霉素诱导的H9c2心肌细胞的影响及机制研究

目的:探讨熊去氧胆酸(UDCA)对阿霉素(DOX)诱导的H9c2心肌细胞损伤的影响及机制。方法:体外培养H9c2细胞,1μM DOX和不同浓度UDCA处理H9c2,CCK-8法测定细胞活力;实时定量聚合酶链反应检测心肌细胞凋亡分子Bax及炎症因子IL-1β、IL-6的表达;Western blotting检测UDCA对DOX诱导的心肌细胞凋亡相关蛋白Bax、Bcl2、Caspase3表达水平变化。结果:与对照组相比,DOX组心肌细胞活力减弱;炎症因子IL-1β,IL-6表达上调;促凋亡分子Bax和cleaved Caspase3表达增多;抑制凋亡蛋白Bcl2下调(P<0.05)。与DOX组相比,UDCA+DOX组显著恢复心肌细胞活力;炎症因子IL-1β、IL-6表达下调;促凋亡分子Bax、cleaved Caspase3下调;抑制凋亡蛋白Bcl2表达上调(P<0.05)。结论:UDCA能缓解DOX诱导的H9c2心肌细胞损伤,其机制可能与抑制炎症及凋亡有关。本研究为阿霉素心肌毒性的防治提供新的实验基础及理论依据。

Effects of Ursodeoxycholic Acid on Doxorubicin-induced Injury in H9c2 Cardiomyocytes and Its Mechanism

Objective: To investigate the effect of Ursodeoxycholic Acid(UDCA) on doxorubicin(DOX)-induced cardiotoxicity in H9 c2 cardiomyocytes and the mechanisms. Methods: The H9 c2 cardiomyocytes were treated with DOX with or without UDCA of different doses. The cell viability was measured by CCK-8 assay, and the inflammatory factors were examined by quantitative real-time polymerase chain reaction(qRT-PCR). As for apoptosis, Western blotting, qRT-PCR were used to analyze. Results: Compared with control group, the viability of H9 c2 cells, the anti-apoptotic protein Bcl2 were decreased(P<0.05). Additionally, the release of inflammatory factors(IL-1β, IL-6), apoptotic molecules(Bax and Cleaved Caspase3) was increased(P<0.05). Compared with DOX group, UDCA+DOX group restored the cell viability, ameliorated the release of inflammatory factors(IL-1β, IL-6), inhibited pro-apoptotic molecules(Bax and Cleaved Caspase3), promoted anti-apoptotic molecules Bcl2 as well(P<0.05). Conclusions: UDCA suppresses DOX-induced injury in H9 c2 cardiomyocytes by reducing inflammation and apoptosis, which provides a pivotal theoretical basis for the clinical application of UDCA in the prevention and treatment of DOX-induced cardiotoxicity.