人参皂苷Rg1抑制PGF2α诱导心肌细胞肥大

Ginsenoside Rg1 inhabits cardiomyocyte hypertrophy induced by prostaglandin F_(2α)

目的观察人参皂苷Rg1(ginsenoside Rg1,Rg1)对前列腺素F2α(prostaglandin F2α,PGF2α)所致心肌肥大的影响。方法利用培养的新生大鼠心肌细胞,以细胞直径、蛋白含量?心房利钠因子(atrial natriuretic factor,ANF)mRNA的表达为心肌肥大标志,观察药物的抗心肌肥大效应。AN-FmRNA的表达用Real-time PCR检测;用Fura-2/AM负载的培养心肌细胞检测细胞内游离钙浓度([Ca2+]i);一氧化氮试剂盒测定细胞上清液中一氧化氮(nitric oxide,NO)代谢物的含量,以探讨Rg1可能的作用机制。结果PGF2α0.1μmol·L-1使心肌细胞直径明显增大,蛋白质含量明显增加,ANF mRNA的表达增强,并使[Ca2+]i明显升高。Rg115.6、31.2和62.4μmol·L-1使经PGF2α处理的心肌细胞的直径分别缩短18.4%、32.7%和43.8%;使心肌细胞蛋白含量分别减少8.2%、14.6%和17.7%;Rg1 62.4μmol·L-1还使ANF mRNA的表达降低;Rg1 15.6、31.2和62.4μmol·L-1呈剂量依赖地抑制PGF2α所致的[Ca2+]i升高;NO前体L-精氨酸(L-arg)1 mmol.L-1具有相似的作用。此外,NO合酶抑制剂L-NAME可取消L-arg的作用,并部分抑制Rg1的效应;Rg1还明显升高心肌细胞上清液NO代谢物的含量。结论Rg1可抑制PGF2α诱导的心肌细胞肥大,该作用可能与其促进心肌细胞NO的释放,降低由PGF2α所升高的心肌细胞[Ca2+]i有关。

Aim To study the effect of ginsenoside Rgl （Rgl）on cardio myocyte hypertrophy induced by prostaglandin F2α（ PGF2α） , and to probe primarily into its mechanism. Methods The cultured neonatal rat cardiomyocyte hypertrophic response and the antihypertrophic effects of Rgl were observed by measuring the cell diameter, protein content and the expression of atrial natriuretic factor （ANF） mRNA, which was assayed by real-time PCR. For mechanism studies, the intracellular free calcium concentration （ [ Ca^2＋ ] i ） in cultured cardiomyocytes was measured by using Fura- 2/AM as a fluorescent indicator, nitric oxide （NO） metabolite level in the culture medium was tested by using Nitric Oxide Synthase Detection Kit. Results PGF2α 0. 1 la,mol · L^-1 caused the increases in the cardiomyocyte cell diameter, protein content and the ex- pression of ANF mRNA. It could increase the [ Ca^2 ＋ ] i in cultured cardiomyocytes. Rgl 15.6, 31.2, 62. 4 la,mol · L^-1 could concentration-dependently inhibit the cardiomyocyte hypertrophy induced by PGF2,, and the cell diameter of cardiomyocyte treated by PGF2, was decreased by 18.4% ,32. 7% ,43.8% （ P 〈 0. 01 ） ; the protein content was reduced by 8.2%, 14. 6%, 17. 7% （ P 〈 0. 01 ）, respectively. Furthermore, the elevated ANF mRNA expression induced by PGF2, was also inhibited by Rgl. L-arginine（L-arg）, a precursor of NO, had similar effects with Rgl at 1 mmol · L^-1. The NOS inhibitor L-NAME （ 1 mmol · L^-1 ） could a- bolish the effects of L-arg, and inhibit partly the effects of Rgl, and Rgl could increase the metabolite of NO in the cultured medium. Conclusion Rgl could in- hibit the cardiomyocyte hypertrophy induced by PGF2,, which might be related to its promoting effect on the re- lease of NO and its inhibitory effect on the elevated [ Ca^2 ＋ ] i induced by PGF2a.