miRNA-1与糖尿病心肌病心肌细胞肥大相关性的初步探讨  

Association of miRNA-1 Expression and Cardiomyocyte Hypertrophy in Diabetes

作　　者：李雯琦[1] 刘书雷[1] 徐明彤[2] 黄辉[1] 陈筱潮[1,3] 王景峰[1,3] 

机构地区：[1]中山大学附属孙逸仙纪念医院心内科,广东广州510120 [2]中山大学附属孙逸仙纪念医院内分泌科,广东广州510120 [3]广东省心电生理和心律失常重点实验室,广东广州510120

出　　处：《中山大学学报（医学科学版）》2013年第2期170-175,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81270915);广东省自然科学基金(S2011010001614);广州市科技计划重点项目(12C21121666)

摘　　要：【目的】观察糖尿病大鼠动物模型心脏及大鼠离体心肌细胞在高糖诱导下miRNA-1的表达水平,测定心肌细胞的大小、蛋白含量以及ANP和BNP的表达,并探讨其相关性。【方法】STZ诱导建立糖尿病大鼠模型(模型组15只,对照组10只),在成模后8周进行心功能、心肌肥大相关基因ANP和BNP mRNA、miRNA-1的检测。并分离原代乳鼠心肌细胞进行培养,在24 h、48 h和72 h时间点动态观察正常糖浓度(5 mmol/L)和高糖浓度(30 mmol/L)心肌细胞miRNA-1表达的差异,并分析比较不同葡萄糖浓度培养下心肌细胞的直径、蛋白质含量以及心肌细胞肥大基因的表达,统计分析高糖浓度培养心肌细胞miRNA-1表达与心肌细胞肥大相关指标的相关性。【结果】糖尿病大鼠模型8周末显示心功能障碍,miRNA-1较对照组明显下降,ANP及BNP mRNA明显升高,组间差别均有统计学意义。高糖诱导大鼠离体心肌细胞miRNA-1的总量随时间呈先升后降趋势并有统计学意义(F=15.109,P=0.001);高糖刺激使心肌细胞直径、心肌细胞蛋白含量随培养的时间延长而逐步增高,并明显大于正常糖浓度培养下的心肌细胞;高糖刺激时心肌细胞ANP及BNP mRNA表达变化趋势与miRNA-1表达一致,ANPmRNA表达与miRNA-1存在线性相关(r=0.990,P=0.01)。【结论】糖尿病大鼠心肌组织及高糖培养诱导原代乳鼠心肌细胞miRNA-1发生明显改变,乳鼠心肌细胞miRNA-1表达与心肌细胞肥大变化相一致,与心肌细胞ANP的表达变化呈线性相关。[ Objective ] To investigate the relationship between expression of miRNA-1 and cadiomyocyte hypertrophy in diabetic rats in vivo and in vitro. [ Methods ] The cardiac function, ANP mRNA, BNP mRNA, and miRNA-1 in the hearts of STZ induced diabetic rats 8 weeks after the establishment of model were observed respectively （nDCM = 15, nNC =10）. Neonatal rat cardiomyocytes were isolated and cultured in 5 mmol/L glucose （normal glucose, NG） or 30 mmol/L glucose （high glucose, HG） for 24, 48, and 72 hours. The expression of miRNA- 1 was examined on each time point, so as to the cellular diameters, protein level, ANP mRNA and BNP mRNA. The relationship between miRNA-1 and hypertrophic effect caused by high glucose was analyzed. [ Results ] After 8 weeks of diabetes, diabetic rats showed cardiac dysfunction, decrease of miRNA- 1 and increase of ANP and BNP mRNA. The expression of miRNA-1 in HG group increased at first and decreased afterwards （F = 15.109, P = 0.001 ）. The changes of cellular diameters and protein level in HG group were gradually increased with cultured time and significantly higher than those in NG group. The expressive tendency of ANP and BNP mRNAs in HG group were similar with the expression of miRNA- 1. Particularly, the expression of ANP mRNA positively correlated with the expression of miRNA-1 （r = 0.990, P = 0.01 ）. [ Conclusion] High glucose induced the alteration of miRNA-1 expression in neonatal rat cardiomyocytes and diabetic rats. This alteration of miRNA-1 in neonatal rat cardiomyocytes was accompanied by increase of cardiomyocyte diameter and cellular protein level. The expression of ANP mRNA was related with the expression of miRNA- 1 positively.

关 键 词：糖尿病心肌病 miRNA-1 心肌肥大 ANP 

分 类 号：R363[医药卫生—病理学]