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延胡索乙素对大鼠急性心肌梗死的心脏保护作用。

Cardioprotective Effects of Tetrahydropalmatine on Acute Myocardial Infarction in Rats.

机构信息

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China.

Institute of Traditional Chinese Medicine, Shandong Hongjitang Pharmaceutical Group Co., Ltd., Jinan 250103, P. R. China.

出版信息

Am J Chin Med. 2022;50(7):1887-1904. doi: 10.1142/S0192415X2250080X. Epub 2022 Sep 4.

Abstract

Tetrahydropalmatine (THP) is an active component of . The current study investigates the possible cardioprotective effects of tetrahydropalmatine in acute myocardial ischemia (AMI) rats. The anterior descending coronary artery of SD rats was ligated to establish an AMI model. After two weeks of gavage of THP, cardiac function was determined by echocardiography. The organ index and the infarct size were assessed after the experiment, and the histopathological myocardial tissue changes were observed. In addition, the apoptosis index of myocardial cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of SOD, MDA, CAT, GSH-Px, BNP, and cTn-I were measured by enzyme-linked immunosorbent assay. To determine relevant proteins, the Western blot and molecular docking were applied. Compared with the model group, THP could enhance rat cardiac ejection function to improve cardiac function, drastically lessen the infarct size, reduce myocardial cell damage and inflammatory cell infiltration. THP might also prevent ischemic myocardial damage by inhibiting myocardial cell apoptosis and efficiently reducing oxidative stress. Specifically, THP could decrease MDA, BNP, c-TnI activities, as well as the expression of Bax and Caspase-3 protein, while increasing SOD, GSH-Px, CAT activities, and Bcl-2 level. Furthermore, THP could significantly promote the phosphorylation of PI3K and Akt proteins. The involved pathways and proteins have also been verified through molecular docking. According to these findings, THP may preserve the myocardium due to its anti-oxidant and anti-apoptotic properties.

摘要

延胡索乙素(THP)是 的一种活性成分。本研究旨在探讨延胡索乙素对急性心肌缺血(AMI)大鼠的可能心脏保护作用。结扎 SD 大鼠的前降支冠状动脉以建立 AMI 模型。灌胃 THP 两周后,通过超声心动图测定心功能。实验结束后评估器官指数和梗死面积,并观察心肌组织的病理变化。此外,通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)测定法检测心肌细胞的凋亡指数。通过酶联免疫吸附试验测定 SOD、MDA、CAT、GSH-Px、BNP 和 cTn-I 的水平。应用 Western blot 和分子对接确定相关蛋白。与模型组相比,THP 可增强大鼠心脏射血功能,改善心功能,显著减小梗死面积,减轻心肌细胞损伤和炎性细胞浸润。THP 还可能通过抑制心肌细胞凋亡和有效降低氧化应激来防止缺血性心肌损伤。具体而言,THP 可以降低 MDA、BNP、c-TnI 的活性以及 Bax 和 Caspase-3 蛋白的表达,同时增加 SOD、GSH-Px、CAT 的活性和 Bcl-2 水平。此外,THP 可以显著促进 PI3K 和 Akt 蛋白的磷酸化。通过分子对接也验证了涉及的途径和蛋白。根据这些发现,THP 可能通过抗氧化和抗凋亡特性来保护心肌。

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