二甲双胍对糖尿病大鼠心肌病理变化及凋亡相关基因的影响
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Changes of Pathology and Apoptosis Associated Genes in the Diabetic Rat Myocyte Affected by Metformin
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    目的观察二甲双胍对2型糖尿病大鼠心肌病理变化及心肌细胞中survivin、p27、c-myc及c-fos mRNA和蛋白变化的影响。方法建立糖尿病大鼠模型,35只糖尿病大鼠随机分为糖尿病组和二甲双胍组,另选15只大鼠作为正常对照组。喂养6周后,利用光镜和病理染色观察心肌病理改变,用RT-PCR检测心肌survivin、p27、c-myc及c-fos mRNA表达,用Western blot检测心肌survivin、p27、c-myc及c-fos蛋白表达。结果正常对照组心肌纤维排列整齐,心肌间质及血管周围间质成分少;糖尿病组心肌细胞肥大、水肿,心肌纤维排列紊乱,细胞间隙增宽,心肌间质成分明显增多,血管周围基质明显增多,可见较多炎性细胞浸润;二甲双胍组心肌纤维排列整齐,细胞间隙较窄,心肌间质和血管周围基质较少,少量炎性细胞浸润。二甲双胍组c-fos mRNA和蛋白的表达与正常对照组比较无显著性差异,但明显高于糖尿病组(P<0.05);二甲双胍组p27 mRNA和蛋白的表达明显低于正常对照组(P<0.05),且与糖尿病组比较无显著性差异(P>0.05);二甲双胍组c-myc mRNA和蛋白的表达与正常对照组和糖尿病组比较无显著性差异(P>0.05);二甲双胍组survivin mRNA和蛋白的表达低于正常对照组,高于糖尿病组,但无显著性差异(P>0.05)。结论糖尿病大鼠心肌病理改变与survivin、p27、c-fos mRNA及蛋白表达有关。二甲双胍对糖尿病心肌具有保护作用,其分子机制可能与改变心肌c-fos mRNA及蛋白的表达有关,而可能与survivin、p27、c-myc mRNA及其蛋白表达水平无关。

    Abstract:

    AimTo explore the effects and relative mechanism of metformin on changes of apoptosis associated genes survivin, p27, c-myc, c-fos and pathology in the diabetic rat myocyte.MethodsThe diabetic rat model was established.35 diabetic rats were randomly allocated into metformin(MT) group and diabetes mellitus(DM) group.15 rats were selected as control group.Therapeutical effect of myocardial pathology was detected by optical microscope and pathologic chemical staining.Apoptosis associated genes survivin, p27, c-myc, c-fos mRNA and relative proteins in the myocardium were detected by RT-PCR and Western blot. ResultsPathology of the DM group: myocyte arranged irregularly, myocyte hypertrophy, distortion, enlarged intercellular space, increased extracellular matrix, enhanced inflammatory cell infiltration, myocyte edema and more interstitial fibroblasts were observed.The changes of the myocardium in the MT group were significantly relieved compared with those of the DM group, myocyte ranked in order, interstitial contents decreased, perivascular matrix decreased, fibroblast decreased, inflammatory cell infiltration reduced markedly.The pathology changes of DM group were related to changes of survivin, p27, c-fos mRNA and protein. c-fos mRNA and protein level in MT group had no significant difference compared with the control group (p>0.05), but it was significantly higher than that of DM group (p<0.05). Survivin, p27 and c-myc mRNA and protein level in MT group had no significant difference compared with the DM group (p>0.05).ConclusionsThe pathology changes of DM group is related to changes of survivin, p27, c-fos mRNA and protein. Metformin improves pathological changes of diabetic cardiomyopathy which may be related to change of c-fos mRNA and protein.Metformin’s protective effect may not be related to survivin, p27 and c-myc mRNA and protein.

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纪征,张琦,邸亚丽.二甲双胍对糖尿病大鼠心肌病理变化及凋亡相关基因的影响[J].中国动脉硬化杂志,2012,20(4):340~344.

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  • 收稿日期:2011-06-28
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