MiR-182模拟物提高1型糖尿病小鼠的心脏功能
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国家自然科学基金面上项目(NO.81270208)。


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

    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。

    Abstract:

    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 ultrasonic 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 ① MiR-182 mimics improved the cadiac function of type 1 diabetic mice with an increase of left ventricular function and left ventricular short axis fractional shortening (P<0.01);② MiR-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 ultrastructural 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 hypertrophy-related gene ANP,β/α-MHC ratio and expression of Col Ⅰ, Col Ⅲ, reduction of mitochondrial damage and autophagy.

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孟哲颖,王玉,南淑良,林艳端,徐卫平,胡兵,申锷. MiR-182模拟物提高1型糖尿病小鼠的心脏功能[J].中国实验动物学报,2014,22(4):1~5.

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  • 收稿日期:2014-04-24
  • 最后修改日期:2014-02-27
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  • 在线发布日期: 2014-05-06
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