L-精氨酸对高糖高胰岛素诱导心肌细胞肥大的抑制作用  

Inhibitory Effect of L-Arginine on Cardiomyocyte Hypertrophy Induced by High Glucose and Insulin

作　　者：邱红梅[1] 王明丰[1] 吴芹[2] 蒋青松[1] 

机构地区：[1]重庆医科大学药理教研室生物化学与分子药理学重庆市重点实验室,重庆400016 [2]贵州遵义医学院药理教研室贵州省重点药理实验室,贵州遵义563003

出　　处：《中国生物制品学杂志》2010年第7期692-695,共4页Chinese Journal of Biologicals

摘　　要：目的探讨L-精氨酸(L-Arg)对高糖高胰岛素(High glucose and insulin,HGI)诱导心肌细胞肥大的抑制作用。方法体外培养乳鼠心肌细胞,将细胞分为正常对照组(5.5mmol/L葡萄糖)、模型组(HGI组,给予25.5mmol/L葡萄糖与0.1μmol/L胰岛素)、L-Arg低、中、高剂量组(给予HGI组药物,并分别加入0.01、0.1和1.0mmol/L的L-Arg)和L-Arg+L-NAME组[给予HGI组药物,并加入0.1mmol/LL-Arg和一氧化氮合酶(Nitric oxide synthase,NOS)特异性抑制剂L-NAME],以细胞表面积、蛋白质含量和心房利钠因子(Atrial natriuretic factor,ANF)mRNA表达为反映心肌肥大的指标,观察L-Arg对HGI致心肌细胞肥大作用的影响;采用Real-timePCR法检测内皮型一氧化氮合酶(Endothelial NOS,eNOS)和诱生型一氧化氮合酶(Inducible NOS,iNOS)mRNA的表达;比色法和硝酸还原法分别检测细胞培养液中NOS的活性和NO的含量。结果 L-Arg呈浓度依赖性地抑制HGI诱导的心肌细胞肥大;并上调eNOS mRNA的表达及NOS的活性,增加NO的浓度。NOS抑制剂L-NAME可完全阻断L-Arg的上述作用。结论 L-Arg可通过激活eNOS表达,促进NO释放,产生抗HGI诱导心肌肥大的作用。Objective To investigate the inhibitory effect of L-arginine（L-Arg）on the cardiomyocyte hypertrophy induced by high glucose and insulin（HGI）.Methods The cardiomyocytes of suckling mice were cultured in vitro and divided into normal control,model（HGI）,L-Arg at low,moderate and high dosages and L-Arg ＋ L-NAME groups,and treated with 5.5 mmol /L glucose,25.5 mmol /L glucose ＋ 0.1 μmol /L insulin,25.5 mmol /L glucose ＋ 0.1 μmol /L insulin ＋ 0.01,0.1 and 1.0 mmol /L L-Arg and 25.5 mmol /L glucose ＋ 0.1 μmol /L insulin ＋ 0.1 mmol /L L-Arg ＋ L-NAME [a nitric oxide synthase（NOS）-specific inhibitor]respectively.The effect of L-Arg on cardiomyocyte hypertrophy was observed using cell surface area,protein content and atrial natriuretic factor（ANF）mRNA expression as indicators.The expressions of mRNAs of endothelial NOS（eNOS）,and inducible NOS（iNOS）were determined by real-time PCR.The NOS activity and NO content in cell culture were determined by colorimetry and nitrate reduction method respectively.Results L-Arg showed a dosage-dependent inhibitory effect on the cardiomyocyte hypertrophy induced by HGI,while up-regulated the expression of eNOS mRNA and NOS activity and increased the NO content.However,L-NAME blocked all the effects of L-Arg completely.Conclusion L-Arg inhibited the HGI-induced cardiomyocyte hypertrophy by activating the expression of eNOS and promoting the release of NO.

关 键 词：精氨酸 一氧化氮 肌细胞 心脏 高糖高胰岛素 糖尿病 

分 类 号：R542.2[医药卫生—心血管疾病]