钙调神经磷酸酶信号通路参与PGF_(2α)诱导的心肌细胞肥大  

Calcineurin signal transduction pathway involves in cardiomyocyte hypertrophy induced by prostaglandin F_(2α)

作　　者：蒋青松[1] 黄燮南[2] 周岐新[1] 杨贵忠[2] 戴支凯[2] 吴芹[2] 石京山[2] 

机构地区：[1]重庆医科大学药理教研室,重庆400016 [2]遵义医学院药理教研室,贵州遵义563003

出　　处：《中国病理生理杂志》2007年第7期1272-1276,共5页Chinese Journal of Pathophysiology

基　　金：贵州省科技厅资助项目[No(2004)3057]

摘　　要：目的:研究前列腺素F2α(PGF2α)诱导心肌细胞肥大的作用及其细胞内信号转导通路。方法:利用乳鼠心肌细胞培养,以细胞直径、蛋白质含量和心房利钠因子(ANF)mRNA表达为心肌肥大反应指标,观察PGF2α致心肌肥大效应。采用Fura-2/AM为荧光指示剂测定心肌细胞内钙浓度([Ca2+]i);RT-PCR法半定量测定mRNA表达;Western blotting方法检测蛋白表达。结果:随着PGF2α浓度升高(10-10-10-5mol/L),心肌细胞直径、蛋白含量和[Ca2+]i均明显高于溶剂对照组(P(0.01);PGF2α10-7mol/L使ANF mRNA表达明显高于对照组(P(0.01);钙调神经磷酸酶(CaN)mRNA及CaN信号通路(含CaN及其下游因子NFAT3和GATA4)蛋白的表达亦明显高于对照组(P(0.05)。加入CsA(CaN阻断剂)后,PGF2α诱导的心肌细胞肥大和[Ca2+]i升高的作用明显降低(P(0.01),CaN mRNA和CaN信号通路蛋白的表达亦明显减少(P(0.05)。结论:PGF2α诱导的心肌细胞肥大至少部分与其升高[Ca2+]i从而激活CaN信号转导通路有关。AIM： To study the role of prostaglandin F2α （PGF2α） in cardiac hypertrophy and its relation with calcineurin （CaN） signal transduction pathway in vitro. METHODS ： The cultured neonatal rat cardiomyocyte was used to observe the hypertrophic effect of PGF2α, and the hypertrophic response was assayed by measuring the cell diameter, protein content and atrial natriuretic factor （ANF） mRNA expression. 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. ANF and CaN mRNA expressions, and the expressions of CaN and its downstream effectors, NFAT3 and GATA4 proteins were assayed by RT - PCR and Western blotting, respectively. RESULTS ： In cultured cardiomyocytes, PGF2α induced profound hypertrophic morphology change, the significant increase in cell diameter and protein content in a concentration - dependent manner compared with those in vehicle control （ P 〈 0.01 ）. The same result was found in measuring the [ Ca^2＋] i in cardiomyocytes （P 〈0.01 ）. PGF2α at concentration of 10^-7 mol/L significantly promoted ANF and CaN mRNA expressions and the protein expressions of CaN/NFAT3/GATA4 compared with those in the vehicle control （P 〈0.05）. Cyclosporin A, a CaN inhibitor, markedly inhibited the myocyte hypertrophy （ P 〈 0.01 ）, reduced the increased [ Ca^2＋ ]i （ P 〈0.01 ） and decreased the expressions of CaN mRNA and CaN/NFAT3/GATA4 proteins （ P 〈0.05 ） compared with those of only PGF2α 10^-7 mol/L treatment. CONCLUSION： Cardiomyocyte hypertrophy induced by.PGF2α, may be, at least in part, mediated by CaN signal transduction pathway activated by increasing [ Ca^2＋] i.

关 键 词：前列腺素F类 心肌肥大 信号转导 钙神经素 

分 类 号：R363[医药卫生—病理学]