【摘要】 目的探讨人参皂苷Rg1(ginsenoside Rg1,Rg1)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)所致心肌细胞肥大的影响,并初探其分子机制。方法在培养的新生大鼠心肌细胞中加入AngⅡ0.1μmol.L-1,HE染色观测细胞形态学变化,并以心肌细胞直径?蛋白含量和心房利钠因子(atrial natriuretic factor,ANF)mRNA的表达为肥大指标。为分析药物的作用机制,用Fura-2/AM负载心肌细胞检测细胞内游离钙浓度[Ca2+]i;并检测钙调神经磷酸酶(calcineurin,CaN)mRNA的表达变化。ANF和CaN mRNA的表达采用Real-time PCR测定。结果AngⅡ0.1μmol.L-1使心肌细胞直径明显增大,蛋白质含量明显增加,并使ANF mRNA的表达显著升高。加入Rg1 15.6、31.2和62.4μmol.L-1使AngⅡ所增大的心肌细胞直径分别缩短13%、33%、43%(P<0.01);并使心肌细胞蛋白含量分别减少10%、14%和19%(P<0.01),Rg1 62.4μmol.L-1还显著抑制AngⅡ所上调的ANF mRNA的表达。与此同时,上述浓度的Rg1还使AngⅡ所升高的[Ca2+]i分别抑制了19.3%?28%和38.6%(P<0.01,n=6);Rg1 62.4μmol.L-1还使AngⅡ所升高CaN mRNA的表达明显降低。结论Rg1可抑制AngⅡ诱导的心肌细胞肥大,该作用可能与其降低由AngⅡ所升高的心肌细胞[Ca2+]i,并由此而抑制Ca2+-CaN信号通路有关。更多还原

【Abstract】 OBJECTIVE To observe the effects of ginsenoside Rg1(Rg1)on cardio myocyte hypertrophy induced by angiotensin Ⅱ(AngⅡ),and to investigate its molecular mechanism.METHODS AngⅡ-induced neonatal rat cardiomyocyte hypertrophic responses and the antihypertrophic effects of Rg1 were assayed by measuring the cell diameter,protein content and the expression of atrial natriuretic factor(ANF) mRNA.For analyzing the antihypertrophic mechanism,the intracellular free Ca2+ concentration(i) and the calcineurin(CaN) mRNA expression in cultured cardiomyocytes were measured by using Fura 2/AM as fluorescent indicator and by Real-time PCR,respectively.RESULTS AngⅡ 0.1 μmol·L-1 induced significantly the increases of the cell diameter,protein content and the expression of ANF mRNA in cultured cardiomyocytes.Ginsenoside Rg1 15.6,31.2,62.4 μmol·L-1 concentration-dependently inhibited the elevated cell diameter by 13%,33% and 43%(P<0.01,n=3),and the elevated protein content by 10%,14% and 19%(P<0.01,n=6),compared with AngⅡ-model group.The up regulated ANF mRNA expression induced by AngⅡ was significantly decreased by Rg1 62.4 μmol·L-1.The increase of AngⅡ-induced i was inhibited by 19.3%,28% and 38.6%,respectively,and 62.4 μmol·L-1 Rg1 remarkably decreased the expression of CaN mRNA.CONCLUSION Rg1 can inhibit the cardiomyocyte hypertrophy induced by AngⅡ,which may be related to its inhibitory effect on the elevated i,resulting in inactivation of CaN transduction pathway.更多还原