白藜芦醇对异丙肾上腺素诱导心肌细胞肥大的抑制作用

The inhibitory effects of resveratrol on myocardical hypertrophy induced by isoprenaline

目的:探讨白藜芦醇对异丙肾上腺素(ISO)诱导的乳鼠心肌细胞肥大的作用及其可能机制。方法:异丙肾上腺素10μmol/L诱导心肌细胞肥大,实验分为:正常组、异丙肾上腺素组、白藜芦醇25μmol/L组、白藜芦醇50μmol/L组、N-[2-[N-(4-氯肉桂)-N-甲基氨基]苯基]-N-(2-羟乙基)-4-甲氧苯磺酰胺磷酸酯盐(KN93)0.2μmol/L组。Lowry法测心肌细胞蛋白含量;鬼笔环肽染色测细胞大小;RT-PCR测细胞内ANP mRNA表达;Fura-2/AM为荧光探针,观察胞内[Ca2+]i瞬间变化,电泳法测定钙调蛋白激酶(Ca MKⅡ)蛋白表达。结果:异丙肾上腺素使心肌细胞蛋白含量增加,细胞体积增大,ANP mRNA表达增加,[Ca2+]i瞬变增加,Ca MKⅡ蛋白表达增高。与异丙肾上腺素组相比,白藜芦醇50μmol/L和KN93 0.2μmol/L组蛋白含量降低,细胞体积减少,ANP mRNA表达降低,[Ca2+]i瞬变降低,Ca MKⅡ蛋白表达降低。结论:白藜芦醇可通过降低胞内[Ca2+]i瞬变和Ca MKⅡ表达抑制异丙肾上腺素诱导的乳鼠心肌细胞肥大。

Aim： The aim of the present study was to study the protective effect of resveratrol on isoprenaline（ ISO） induced myocardial hypertrophy,and to explore a possible mechanism. Methods： The hypertrophic cardiomyocytes were induced by ISO 10 μmol / L. Experiment was divided into 5 groups： control group,ISO group,resveratrol 25 μmol / L,resveratrol 50 μmol / L,N-[2-N-4-Chlorocinnamyl-N-methylaminomethylphenyl]-N-[2-hydroxyethyl]-4-methoxybenzenesulfonamide（ KN93） 0. 2 μmol / L group. The total protein content was measured by the method of Lowry. The cardiomyocytes size was measured by rhodamine-labeled phalloidin staining; ANP mRNA expression was measured by RT-PCR; [Ca2 ＋]i transient was measured by cell-loading Fura-2 /AM. The expression of calmodulin dependent kinaseⅡ（ Ca MKⅡ） was determined by Western blot. Results： Compared with control group,ISO increased the total protein content,the cardiomyocytes size,ANP mRNA expression,[Ca2 ＋]i transient and the expression of Ca MKⅡ. Compared with ISO group,the protein content,cell size,ANP mRNA expression,[Ca2 ＋]i transient and Ca MKⅡ protein expression were decreased in Resveratrol 50 μmol/L and KN93 0. 2 μmol/L group. Conclusion： Resveratrol has a protective effect on ISO induced myocardial hypertrophy,and the mechanism was related with decreasing [Ca2 ＋]i transient and the Ca MKⅡ signaling pathway.