Liu Shengzhong, He Ying, Shi Jun, Liu Lulu, Ma Hao, He Li, Guo Yingqiang
Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Cardiac Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
J Cell Physiol. 2019 Apr 24. doi: 10.1002/jcp.28556.
Osthole could alleviate myocardial ischemia/reperfusion (I/R) injury. However, the underlying mechanism remains unclear. In this study, we explored whether microRNA (miR)-30a and its target autophagy marker Beclin-1 involved in the osthole protective role in the rat and cells myocardial I/R injury models. The myocardial damages including increases in myocardial collagen content and cell apoptosis in I/R injury model were observed by Masson's Trichrome Staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. Osthole significantly inhibited the myocardial damages. Osthole inhibited the induction of miR-30a expression by I/R in rat and hypoxia/reoxygenation (H/R) in myocardial cells. After knockdown, the expression of miR-30a by miR-30a inhibitor, H/R induced cell apoptosis was significantly inhibited. The level of Beclin-1 expression and ratio of LC3BII/LC3BI were inhibited by I/R in rat and H/R in myocardial cells, whereas osthole significantly increased them. Knockdown of miR-30a significantly upregulated the Beclin-1 expression and ratio of LC3BII/LC3BI. Inhibition of autophagy by 3-MA significantly reversed the protective role of osthole in H/R myocardial cell. Therefore, we concluded that the mechanism by which osthole alleviate myocardial I/R injury may be achieved by enhancing the autophagy partially via inhibiting the expression of miR-30a.
蛇床子素可减轻心肌缺血/再灌注（I/R）损伤。然而，其潜在机制仍不清楚。在本研究中，我们探讨了微小RNA（miR）-30a及其靶标自噬标志物Beclin-1是否参与蛇床子素对大鼠和细胞心肌I/R损伤模型的保护作用。通过Masson三色染色和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）检测观察到I/R损伤模型中心肌损伤，包括心肌胶原含量增加和细胞凋亡。蛇床子素显著抑制心肌损伤。蛇床子素抑制I/R诱导的大鼠miR-30a表达以及心肌细胞缺氧/复氧（H/R）诱导的miR-30a表达。用miR-30a抑制剂敲低miR-30a后，H/R诱导的细胞凋亡得到显著抑制。I/R抑制大鼠和心肌细胞H/R诱导的Beclin-1表达水平及LC3BII/LC3BI比值，而蛇床子素显著升高它们。敲低miR-30a显著上调Beclin-1表达及LC3BII/LC3BI比值。3-MA抑制自噬显著逆转了蛇床子素对H/R心肌细胞的保护作用。因此，我们得出结论，蛇床子素减轻心肌I/R损伤的机制可能是通过部分抑制miR-30a的表达来增强自噬实现的。
