miR-34a 通过抑制 SIRT1 的活性促进大鼠心肌梗死。
MiR-34a promotes myocardial infarction in rats by inhibiting the activity of SIRT1.
机构信息
Department of Cardiology, Changhai Hospital, Shanghai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):7059-7065. doi: 10.26355/eurrev_201908_18750.
OBJECTIVE
To investigate the effect of micro ribonucleic acid (miR)-34a regulating silent information regulator 1 (SIRT1) on myocardial infarction (MI) rats.
MATERIALS AND METHODS
A total of 30 male, 8-week-old rats were divided into three groups, including: sham group (M group), MI group and MI + miR-34a treatment group (miR group). Tissue morphology in the MI region was observed via hematoxylin-eosin (HE) staining. Myocardial apoptosis in the three groups was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Furthermore, the protein levels of SIRT1, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in myocardial cells were detected via Western blotting.
RESULTS
Compared with M group, left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) increased significantly in MI group and miR group (p<0.05), while left ventricular ejection fraction (LVEF) and fractional shortening (FS) decreased obviously (p<0.05). The results of HE staining showed that the inflammatory infiltration of myocardial cells and intercellular collagen fibers significantly increased, and the neuronal damage was remarkably aggravated in MI group and miR group when compared with M group (p<0.05). Compared with MI group, myocardial necrosis, inflammatory cell infiltration and intercellular collagen fibers all increased significantly in miR group (p<0.05). Moreover, the results of TUNEL assay revealed that myocardial apoptosis rate in MI group [(21.35±3.12)%] was remarkably higher than that of M group [(9.53±1.17)%]. Meanwhile, it was significantly higher in miR group [(42.38±3.44)%)] than that of MI group, displaying statistically significant differences (p<0.05). The number of apoptotic cells increased obviously in MI group when compared with M group, while it decreased significantly in MI group when compared with miR group (p<0.05). Besides, the protein levels of SIRT1 and Bcl-2 in myocardial tissues in miR group were remarkably lower than those of M group and MI group (p<0.05). Furthermore, the protein level of Bax in miR group was higher than that of M group and MI group, and there were statistically significant differences (p<0.05).
CONCLUSIONS
Overexpression of miR-34a inhibits the activity of SIRT1, thereby promoting the apoptosis of MI.
目的
研究微小 RNA-34a（miR-34a）调控沉默信息调节因子 1（SIRT1）对心肌梗死（MI）大鼠的影响。
材料与方法
雄性 8 周龄大鼠 30 只，随机分为三组：假手术组（M 组）、MI 组和 MI+miR-34a 治疗组（miR 组）。苏木精-伊红（HE）染色观察 MI 区组织形态。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）法检测三组心肌细胞凋亡。Western blot 法检测心肌细胞中 SIRT1、B 细胞淋巴瘤-2（Bcl-2）和 Bcl-2 相关 X 蛋白（Bax）的蛋白水平。
结果
与 M 组比较，MI 组和 miR 组左心室舒张末期直径（LVEDD）和左心室收缩末期直径（LVESD）明显增大（P<0.05），左心室射血分数（LVEF）和短轴缩短率（FS）明显降低（P<0.05）。HE 染色结果显示，MI 组和 miR 组心肌细胞炎症浸润和细胞间胶原纤维明显增加，神经元损伤明显加重（P<0.05）。与 MI 组比较，miR 组心肌坏死、炎症细胞浸润和细胞间胶原纤维明显增加（P<0.05）。此外，TUNEL 检测结果显示，MI 组心肌细胞凋亡率[（21.35±3.12）%]明显高于 M 组[（9.53±1.17）%]，miR 组[（42.38±3.44）%]明显高于 MI 组，差异均有统计学意义（P<0.05）。与 M 组比较，MI 组凋亡细胞数量明显增多，miR 组明显减少（P<0.05）。此外，miR 组心肌组织中 SIRT1 和 Bcl-2 蛋白水平明显低于 M 组和 MI 组（P<0.05），Bax 蛋白水平明显高于 M 组和 MI 组，差异均有统计学意义（P<0.05）。
结论
miR-34a 过表达抑制 SIRT1 活性，从而促进 MI 细胞凋亡。
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