Aim To determine the interaction between endogenous IMD and cardiomyocyte hypertrophy. Method Myocyte hypertrophy was induced by treating the cells with angiotensin II ( Ang II ). Radioim-munoassay and Western blot analysis were used to determine IMD content in cultured neonatal rat ventricular myocytes, real-time PCR was used to measure mR-NA levels of IMD and the IMD receptor components calcitonin receptor-like receptor ( CRLR ) and receptor activity modifying proteins ( RAMPs ) , and the hyper-trophic response was characterized by a significant increase in [ 3H ]-Leu incorporation and BNP mRNA expression. Results Angiotensin II led to an obviousdecrease in the production, secretion, and mRNA expression of IMD and Ang II also influenced the mRNA expression of CRLR/RAMPs. In contrast, treatment with IMD antibody and specific antagonists of the IMD receptor potentiated the Ang II induced hypertrophic response in neonatal cardiomyocytes. Conclusion Endogenous IMD and its receptor system are involved in the onset and development of cardiac hypertrophy, which can be a potential therapeutic way for cardiac hypertrophy.%目的 研究内源性中叶素(IMD)与心肌细胞肥大间的相互作用关系.方法 血管紧张素Ⅱ(AngⅡ)孵育乳鼠心肌细胞构建心肌肥大模型.应用Western blot及放射免疫法测定心肌细胞IMD产生和分泌,实时定量PCR(Real-time PCR)方法检测心肌细胞IMD及其受体系统降钙素受体样受体/受体活性修饰蛋白(CRLR/RAMPs)基因表达的变化.并以[3H]-亮氨酸([3H]-Leu)摄入及脑钠素(BNP)基因表达作为心肌细胞肥大的指标.结果 AngⅡ孵育下调心肌细胞IMD生成、表达,并影响其受体系统的基因表达.反过来,利用IMD抗体及其受体阻断剂阻断内源性IMD的生物学效应可增强AngⅡ诱导的心肌细胞肥大反应.结论 内源性IMD及其受体系统参与了心肌肥大的发生、发展,对其生成、表达的干预有可能成为今后防治心肌细胞肥大的新途径.
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