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

Inhibitory Effects of Rimonabant on Cardiomyocyte Hypertrophy Induced by Angiotensin Ⅱ and Its Mechanism Study

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2×105L^(-1),分为空白对照组、模型组、阳性对照组(氯沙坦10μmol/L)和利莫那班低、中、高浓度组 (0.1、1.0、5.0μmol/L),后5组加入0.1μmol/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Ca^(2+)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(CB_1)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Ca^(2+)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Ca^(2+)浓度和CB_1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Ca^(2+)浓度、下调CB_1蛋白表达有关。

OBJECTIVE:To study the inhibitory effects of rimonabant on cardiomyocyte hypertrophy induced by angiotensinⅡ(AngⅡ)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(losartan10μmol/L),rimonabant lowconcentration,medium-concentration and high-concentration groups(0.1,1.0,5.0μmol/L).The latter 5 groups were cultured with 0.1μmol/L AngⅡto 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.