中国临床药理学与治疗学2020，Vol.25Issue(11)：1214-1222,9.DOI:10.12092/j.issn.1009-2501.2020.11.002
联用芝麻素和维生素E抑制PI3K/AKT信号通路改善自发性高血压大鼠的左室纤维化
Inhibition of PI3K/AKT signaling pathway by sesamin and vitamin E improves left ventricular fibrosis in spontaneously hypertensive rats
摘要
Abstract
AIM:Sesamin (Ses) is one of the ma-jor lignans in sesame seeds with antihypertensive and antifibroticactivities, but its effect is weak. In this experiment, we combined vitamin E ( VitE ) and Ses to observe their effects on blood pressure and left ventricular fibrosis in spontaneously hy-pertensive rats (SHRs), and to explore its possible mechanism. METHODS: Male SHRs were randomly divided into SHRs + Ses + VitE group, SHRs + Ses group, SHRs+VitE group, and SHRs model group. Wistar-Kyoto (WKY) rats were setted as a normal control group. After 10 weeks of administration, systolic blood pressure (SBP) of rats was measured by tail cuff method, and the left ventricle was taken to calculate the organ index. Collagen depo-sition was observed by Masson staining, and cardi-ac collagen volume fraction ( CVF ) was analyzed. Expressions of collagen Ⅰ, collagen Ⅲ, transforming growth factor-β1 (TGF-β1 ), connective tissue growth factor ( CTGF ), matrix metalloproteinase-9 ( MMP-9), matrix metalloproteinase inhibitor-1 (TIMP-1), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT) and phosphoinositol 3 kinase (PI3K) were observed by Western blot. RESULTS: SBP, HW/BW, LVW/HW and CVF in SHRs + Ses + VitE group decreased significantly, and the decrease was higher than that in SHRs+Ses and SHRs+VitE group (P<0.01 or P<0.05). The expression of col-lagen Ⅰ, collagen Ⅲ, TGF-1, CTGF, MMP-9, TIMP-1, p-AKT and PI3K in SHRs + Ses + VitE group de-creased significantly, and the decrease was higher than that in SHRs+Ses and SHRs+VitE group (P<0.01 or P<0.05). CONCLUSION:Ses combined with VitE can reduce the expression of TGF-1, CTGF, MMP-9 and TIMP-1 by inhibiting the activation of AKT/PI3K signaling pathway, thus exerting the effect of lowering blood pressure and improving left ventricular fibrosis.关键词
芝麻素/维生素E/自发性高血压大鼠/左心室纤维化/转化生长因子β1/结缔组织生长因子/磷酸肌醇3激酶/蛋白激酶BKey words
sesamin/vitamin E/hypertension/fi-brosis/TGF-β1/CTGF/PI3K/AKT分类
医药卫生引用本文复制引用
张俊秀,沈媛媛,杨解人,郑书国,郝伟..联用芝麻素和维生素E抑制PI3K/AKT信号通路改善自发性高血压大鼠的左室纤维化[J].中国临床药理学与治疗学,2020,25(11):1214-1222,9.基金项目
Funded by National Natural Science Foundation of China(81600645) （81600645）
National Natural Science Foundation of China(81701161) （81701161）
The University Natural Science Research key Project of Anhui Province(KJ2015A192) （KJ2015A192）
