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[钙网蛋白在压力超负荷诱导的心肌肥厚中的潜在作用研究]

[Study on Potential Role of Calreticulin in Pressure Overload Induced Cardiac Hypertrophy].

作者信息

Wu Siyuan, Lu Lihui, Zhao Mingyue, Wu Wenchao, Fu Hua, Liu Xiajing

出版信息

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2016 Jun;33(3):512-9.

Abstract

This study aims to investigate the role of calreticulin in(CRT)pressure overload induced cardiac hypertrophy.In our study,cardiac hypertrophy was induced by left ventricular pressure overload in male SD rats subjected to transverse aortic constriction(TAC)operation.Expression of gene and protein of calreticulin,markers of cardiac hypertrophy and endoplasmic reticulum stress(ERS)were measured with real-time qPCR and Western blot respectively.Meanwhile,atorvastatin(a known ERS inhibitor)and calreticulin-specific small interference ribonucleic acid(siRNA)were used to inhibit the expression of ERS and calreticulin respectively.The experimental data demonstrated that the gene and protein levels of calreticulin,hypertrophic and ERS markers were increased significantly in the heart tissues of TAC rat models after 4weeks.Moreover,atorvastatin administration improved the cardiac function and reduced the expression of calreticulin and ERS markers in TAC rats.In addition,cultured primary neonatal rat cardiomyocytes(NCMs)were treated with norepinephrine(NE),angiotensionⅡ(AngⅡ)or isoprenaline(ISO)to induce hypertrophic phenotype and ERS.The expression of hypertrophic markers was reduced in NCMs transfected with calreticulin-siRNA.The results suggested that calreticulin might be a promising target for the treatment of cardiac hypertrophy.

摘要

本研究旨在探讨钙网蛋白(CRT)在压力超负荷诱导的心肌肥大中的作用。在我们的研究中,通过对雄性SD大鼠进行横向主动脉缩窄(TAC)手术,使其左心室压力超负荷,从而诱导心肌肥大。分别采用实时定量聚合酶链反应(qPCR)和蛋白质免疫印迹法检测钙网蛋白的基因和蛋白表达、心肌肥大标志物以及内质网应激(ERS)。同时,使用阿托伐他汀(一种已知的ERS抑制剂)和钙网蛋白特异性小干扰核糖核酸(siRNA)分别抑制ERS和钙网蛋白的表达。实验数据表明,4周后TAC大鼠模型心脏组织中钙网蛋白的基因和蛋白水平、肥大标志物以及ERS标志物均显著升高。此外,给予阿托伐他汀可改善TAC大鼠的心功能,并降低钙网蛋白和ERS标志物的表达。另外,用去甲肾上腺素(NE)、血管紧张素Ⅱ(AngⅡ)或异丙肾上腺素(ISO)处理原代培养的新生大鼠心肌细胞(NCMs),以诱导肥大表型和ERS。用钙网蛋白-siRNA转染的NCMs中肥大标志物的表达降低。结果表明,钙网蛋白可能是治疗心肌肥大的一个有前景的靶点。

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