Protective Effects of Matrine on Acute Myocardial Hypertrophy Induced by Isoproterenol via Akt/mTOR/p70S6K/eIF4E Signaling Pathway in Rats

PI3K/AKT/mTOR通路 蛋白激酶B 苦参碱 免疫印迹 磷酸化 化学 肌肉肥大 信号转导 内科学 药理学 内分泌学 医学 生物化学 基因 色谱法
作者
Hui Ma,Hongwan Dang,Shijie Wei,Xiaoying Yang,Wenping Zhang
标识
DOI:10.1101/2021.01.15.426879
摘要

Abstract This study aimed to investigate whether matrine (Ma) attenuates isoproterenol (ISO)-induced acute myocardial hypertrophy via activating Akt/mTOR/p70S6K/eIF4E signaling pathway in rats. We collected 42 male Sprague–Dawley rats weighing 300±20g, randomly divided into seven groups (n=6). The myocardial hypertrophy (MH) model was well established by 85 mg/kg ISO. Changes in hemodynamic parameters were recorded using electrocardiogram after 24h with ISO injection. Western blot and real-time polymerase chain reaction were used to evaluate the expression of Akt, mechanistic target of rapamycin (mTOR), p70S6K, and eIF4E. Tissue arrangement of the 200 and 100 mg/kg Ma+ISO groups was regularly smaller than that of the ISO group. For the protein expression, Akt values in the 200 and 100 mg/kg Ma+ISO groups were 1.57- and 1.81-fold higher than in the ISO group, respectively. Moreover, compared with the ISO group, the expression trends of mTOR in the 200, 100, and 50 mg/kg Ma+ISO groups significantly downregulated. The levels of p70S6K and eIF4E reduced in the 200, 100, and 50 mg/kg Ma+ISO groups according to the ISO group (P<0.05). MRNA expression of p70S6K and eIF4E in the ISO group were 1.90- and 6.38-fold higher compared with that in the 100 mg/kg Ma+ISO group. Ma exerted neuroprotective effects against pachyntic injury. Akt activity was accelerated, but activities of mTOR, p70S6K, and eIF4E were inhibited by Ma. Activation of the Akt/mTOR/p70S6K/eIF4E signaling pathway might be the targets for the protective effects of Ma on acute myocardial hypertrophy in rats.
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