利莫那班对血管紧张素Ⅱ诱导心肌细胞肥大的抑制作用及其机制研究
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篇名: 利莫那班对血管紧张素Ⅱ诱导心肌细胞肥大的抑制作用及其机制研究
TITLE:
摘要: 目的:研究利莫那班对血管紧张素Ⅱ(AngⅡ)诱导心肌细胞肥大的抑制作用及其机制。方法:取大鼠心肌细胞接种于6孔板中,密度调整为2×105 L-1,分为空白对照组、模型组、阳性对照组(氯沙坦10 μmol/L)和利莫那班低、中、高浓度组(0.1、1.0、5.0 μmol/L),后5组加入0.1 μmol/L AngⅡ建立心肌肥大细胞模型,然后分别加入相应浓度的药物,培养24 h后,观察并测量每一个视野内球形细胞的直径和细胞数量,检测心肌细胞中Ca2+浓度、一氧化氮(NO)含量、一氧化氮合酶(NOS)活性和Ⅰ型大麻受体(CB1)蛋白表达情况。结果:各组心肌细胞数量差异无统计学意义(P>0.05)。与空白对照组比较,模型组心肌细胞直径明显增大,心肌细胞中Ca2+浓度和CB1蛋白表达水平均明显增加,NO含量和NOS活性明显降低,差异均有统计学意义(P<0.05)。与模型组比较,阳性对照组和利莫那班低、中、高浓度组心肌细胞直径明显缩小,心肌细胞中Ca2+浓度和CB1蛋白表达水平均明显降低,NO含量和NOS活性明显增加,差异均有统计学意义(P<0.05),且利莫那班组作用呈浓度依赖性。结论:利莫那班可抑制AngⅡ诱导的心肌细胞肥大,其作用机制可能与降低Ca2+浓度、下调CB1蛋白表达有关。
ABSTRACT: OBJECTIVE: To study the inhibitory effects of rimonabant on cardiomyocyte hypertrophy induced by angiotensinⅡ(Ang Ⅱ) and its mechanisms. METHODS: Rat cardiomyocytes were incubated in 6 well culture plates with density of 2×105 L-1. They were divided into blank control group, model group, positive control group (losartan10 μmol/L), rimonabant low- concentration, medium-concentration and high-concentration groups (0.1,1.0, 5.0 μmol/L). The latter 5 groups were cultured with 0.1 μmol/L Ang Ⅱ to induce cardiomyocyte hypertrophy model, and then given relevant concentration of drugs. After cultured with 24 h, diameter and number of spherical cells in each field of vision were observed and measured. The Ca2+ concentration, NO content, NOS activity and protein expression of cannabinoid receptor 1(CB1) in cardiomyocyte were determined. RESULTS: There was no statistical significance in the number of cardiomyocyte (P>0.05). Compared with blank control group, the diameter of cardiomyocytes in model group increased, and Ca2+ concentration and protein expression of CB1 in cardiomyocytes were increased significantly; NO content and NOS activity decreased significantly, with statistical significance (P<0.05). Compared with model group, the diameter of cardiomyocytes in positive control group, rimonabant low-concentration, medium-concentration and high-concentration groups were decreased significantly, and Ca2+ concentration and protein expression of CB1 in cardiomyocytes were decreased significantly; NO content and NOS activity increased significantly, with statistical significance (P<0.05), and the effects of the rimonabant groups were dose-dependent. CONCLUSIONS: Rimonabant can inhibite cardiomyocyte hypertrophy induced by AngⅡ, the mechanism of which may be associated with the decrease of Ca2+ concentration and protein expression of CB1.
期刊: 2018年第29卷第21期
作者: 扈晓霞,韩世飞,李晶
AUTHORS: HU Xiaoxia,HAN Shifei,LI Jing
关键字: 利莫那班;血管紧张素Ⅱ;心肌细胞肥大; Ca2+浓度;Ⅰ型大麻受体
KEYWORDS: Rimonabant; AngiotensinⅡ; Cardiomyocyte hypertrophy; Ca2+ concentration; Cannabinoid receptor 1
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