川芎嗪对血管紧张素Ⅱ诱导心肌细胞肥大的影响及其机制  

Effects of Tetramethylpyrazine on Ang II-induced Cardiomyocyte Hypertrophy and the Underlying Mechanisms

作　　者：余良主[1] 李敏才[1] 佘同辉[1] 韩璐[1] 

机构地区：[1]湖北科技学院基础医学院,湖北咸宁437100

出　　处：《中国实验方剂学杂志》2013年第20期154-157,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：湖北省教育厅科学技术研究项目(B20122804);湖北科技学院科学研究项目(BK1104;ZX1201)

摘　　要：目的:探讨川芎嗪(TMP)对血管紧张素II(Ang II)所诱导心肌细胞肥大的抑制作用及其机制。方法:利用Ang II(0.1μmol·L-1)刺激新生大鼠心肌细胞建立肥大细胞模型。培养心肌细胞随机分为6组:对照组,Ang II(0.1μmol·L-1)组,低剂量TMP(0.01 mmol·L-1)组,中剂量TMP(0.1 mmol·L-1)组,高剂量TMP(1 mmol·L-1)组,吡咯烷二硫化氨基甲酸酯(PDTC,100μmol·L-1)组。在给药处理24 h后,收集各组心肌细胞,检测心肌细胞总蛋白含量、β-肌球蛋白重链(β-MHC)mRNA表达量和核因子-κB(NF-κB)蛋白表达量。结果:Ang II刺激导致培养心肌细胞的总蛋白含量[Ang II组(296.7±27.6)mg·L-1,对照组(184.3±11.6)mg·L-1,P<0.05]、β-MHC mRNA表达量(Ang II组0.936±0.059,对照组0.496±0.030;P<0.05)明显增加,这证实心肌肥大的发生;TMP以剂量依赖的方式抑制Ang II诱导的心肌细胞肥大。同时TMP 1mmol·L-1降低Ang II诱导的肥大心肌细胞中磷酸化NF-κB(Ang II组0.861±0.065,TMP组0.655±0.052,P<0.05)和I-κB蛋白的表达量(Ang II组0.785±0.042,TMP组0.525±0.045,P<0.05)。在应用Ang II刺激心肌细胞同时,给予NF-κB抑制剂PDTC也能抑制Ang II诱导的心肌细胞肥大。结论:川芎嗪通过抑制心肌细胞内NF-κB途径,而抑制Ang II诱导的心肌细胞肥大。川芎嗪的这些作用构成了它对心脏疾病具有保护作用的机制之一。Objective：To investigate the inhibitory effects of tetramethylpyrazinee （TMP） on angiotensin Ⅱ （Ang Ⅱ）-induced cardiomyocyte hypertrophy and the underlying mechanisms.Method：Ang Ⅱ-induced cardiomyocyte hypertrophy model was established in isolated neonatal rat ventricular myocytes.The cells were then randomly divided into 6 groups：control group,Ang Ⅱ （0.1 μmol ·L-1） group,low-dose TMP （0.01 mmol ·L-1）group,middle-dose TMP （0.1 mmol · L-1） group,high-dose TMP （1 mmol · L-1） group,pyrolidine dithiocarbamate （PDTC,a NF-κB inhibitor,100 μmol·L-1） group.After 24 h treatment,cardiomyocytes were harvested to measure total protein content by Lowry＇s method,β-myosin heavy chain （β-MHC） mRNA expression by Real-time PCR,and NF-κB content by Western blotting.Result：Ang Ⅱ induced cardiomyocyte hypertrophy characterized by increased total protein content [Ang Ⅱ groupg （296.7 ± 27.6） mg ·L-1 ; control group （184.3 ±11.6） mg ·L-1,P ＜ 0.05] and enhancedβ3-MHC mRNA expression （Ang Ⅱ group 0.936 ± 0.059 ; control group 0.496 ± 0.030,P ＜ 0.05）,while TMP significantly inhibited Ang Ⅱ-induced hypertrophic growth in a dosedependent manner.Meanwhile,TMP （1 mmol ·L-1） also attenuated Ang Ⅱ-induced increase in phosphorylated NF-κB （Ang Ⅱ group 0.861 ± 0.065 ; TMP group 0.655 ± 0.052,P ＜ 0.05） and Ⅰ-κB protein content （Ang Ⅱgroup 0.785 ± 0.042 ; TMP group 0.525 ± 0.045,P ＜ 0.05） in cardiomyocytes.Furthermore,inhibition of NFκB by the specific inhibitor PDTC markedly suppressed Ang Ⅱ-induced hypertrophic responses.Conclusion：Our findings suggested that TMP inhibits Ang Ⅱ-induced cardiomyocyte hypertrophy through suppression of NF-κB pathway,which might contribute to the protective role of TMP in cardiac diseases.

关 键 词：川芎嗪 肥大 心肌细胞 核因子-ΚB 

分 类 号：R285.5[医药卫生—中药学]