MiR-182模拟物提高1型糖尿病小鼠的心脏功能

Improvement of cardiac function by MiR-182mimics in type 1 diabetic mice

目的探讨miR-182模拟物对1型糖尿病小鼠心脏功能的影响及可能作用机制。方法 40只8周龄雄性C57小鼠随机分为正常对照组(n=5),miR-182模拟物对照组(n=5),1型糖尿病组(n=15),1型糖尿病+miR-182模拟物治疗组(n=15)。腹腔注射链脲佐菌素(STZ)建立1型糖尿病动物模型。实验于8周末结束,采用小动物用高分辨超声仪测量小鼠心脏功能;运用透射电镜观察心肌组织超微结构改变;利用real-time PCR技术检测心肌组织β-肌球蛋白重链(β-MHC),α-肌球蛋白重链(α-MHC),心房钠尿肽(ANP),I型(Col I)和III型胶原(Col III)mRNA及miR-182 mRNA的表达含量。结果 1miR-182模拟物可改善1型糖尿病小鼠的心脏功能,增加心脏射血分数及左室短轴缩短率(P<0.01);2miR-182模拟物可降低糖尿病小鼠心肌组织ANP、Col I、Col III的表达及β/a-MHC比值(P<0.01);3miR182模拟物可改善1型糖尿病小鼠心肌超微结构变化,减轻自噬。结论MiR-182模拟物能改善1型糖尿病小鼠的心脏功能,其机制可能与减轻心肌肥大和心肌纤维化,减轻线粒体结构损伤及减轻自噬有关。

Objective To investigate the effects of miR-182 mimics on cardiac function in type 1 diabetic mice and explore the mechanisms of action .Methods Forty 8-week-old C57 mice were randomly divided into 4 groups：control group （n=5）, miR-182 mimics control groups group （n=5）, type 1 diabetes group （n=15） and type 1 diabetes treated by miR-182 mimics （n=15）.Eight weeks after modeling , the cardiac function was evaluated by a high-resolution ultra-sonic imaging system for small animals （Vevo 2100）.The samples of cardiac tissue was used to observe the ultrastructural changes by electron microscopy and to detect the expression levels of β-MHC,α-MHC, ANP, Col I, Col III and miR-182 mRNA .Results ①MiR-182 mimics improved the cadiac function of type 1 diabetic mice with an increase of left ventricu-lar function and left ventricular short axis fractional shortening （ P＆lt;0.01）;②MiR-182 mimics significantly decreased the expression level of ANP , Col I, Col III protein and the ratio of β/α-MHC in cardiac tissue;③MiR-182 mimics induced ul-trastructural changes of cardiac tissue in type 1 diabetic mice and the phenomenon of autophagy .Conclusions MiR-182 mimics may improve the cardiac function of type 1 diabetic mice , which is associated with decreased expression of hypertro-phy-related gene ANP,β/α-MHC ratio and expression of Col I, Col III, reduction of mitochondrial damage and autophagy .