L-精氨酸对糖尿病大鼠心肌损伤的影响
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温州市科技局科研基金资助项目(Y200602039);温州医学院科研发展基金资助项目(XNK04036)


Protective effect of L-arginine on myocardial impairment in diabetic rats
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    摘要:

    目的研究L-精氨酸(L-Arg)对糖尿病(DM)大鼠心肌的保护作用。方法 28只大鼠腹腔注射链脲佐菌素(60 mg/kg)制备DM模型,随机均分为DM组、L-Arg〔300 mg/(kg.d)〕治疗组。另设立正常对照(NC)组(n=12)。用药12周末处死大鼠,用透射电镜观察3组大鼠心肌细胞的形态学改变,采用RT-PCR检测心肌组织内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)、内皮素-1(ET-1)mRNA的表达水平,并测定心肌组织内eNOSi、NOS、Na+-K+-ATP酶、Ca2+-ATP酶活性以及一氧化氮(NO)、ET-1的含量。结果电镜下可见DM组大鼠心肌细胞肌原纤维含量明显减少,肌浆网扩张,线粒体肿胀变性。DM组大鼠eNOS mRNA表达、Na+-K+-ATP酶、Ca2+-ATP酶活性及NO含量明显低于NC组,而ET-1 mRNA表达及ET-1含量明显高于NC组。L-Arg组大鼠心肌病变明显减轻,eNOS mRNA表达、Na+-K+-ATP酶、Ca2+-ATP酶活性及NO含量明显高于DM组,ET-1mRNA表达及ET-1含量明显低于DM组。结论 L-Arg对DM大鼠心肌具有保护作用,其机制可能与L-Arg增加心肌组织NO含量、降低ET-1含量,改善心肌血供有关。

    Abstract:

    Objective To explore the protective effects of L-arginine(L-Arg) on the myocardial tissue of diabetic rats.Methods The rat models of diabetes mellitus(DM)(n=28) were made by intraperitoneal injection of streptozotocin(60 mg/kg),and allocated into DM group(n=14) and L-Arg treatment group(300 mg/(kg·d))(L-Arg group)(n=14) at random.Another 12 normal rats served as normal control group(NC group).After 12 weeks,the rats were sacrificed.Morphological changes in myocardium in 3 groups were observed under transmission electromicroscope(TEM).The mRNA expression levels of endothelial nitric oxide synthase(eNOS),inducible NOS(iNOS) and endothelin(ET-1) in myocardial tissue were determined by reverse transcription polymerase chain reaction(RT-PCR).The activity of eNOS,iNOS,Na+-K+-ATPase,Ca2+-ATPase and the content of NO,ET-1 in myocardial homogenate were also determined.Results In DM rats,TEM examination showed the lysis of myofibril,dilation of sarcoplasmic reticulum and swelling of mitochondria of myocardial tissue.Compared with NC rats,the mRNA expression level of eNOS and the activity of Na+-K+-ATPase,Ca2+-ATPase,as well as the NO content decreased,but the mRNA expression and content of ET-1 increased in DM rats.The pathological changes in myocardium induced by intraperitoneal injection of streptozotocin were reversed in L-Arg group.Compared with DM rats,the mRNA expression level of eNOS,the activity of Na+-K+-ATPase,Ca2+-ATPase and the content of NO increased,but the mRNA expression and content of ET-1 decreased in L-Arg group.Conclusion L-Arg exerts protective effects on diabetic myocardium,which may be through increasing the NO content and decreasing the ET-1 content,so as to improve the blood supply of myocardial tissue.

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董敏,陈秀芳,方周溪,雷康福,管瑜. L-精氨酸对糖尿病大鼠心肌损伤的影响[J].中华老年多器官疾病杂志,2010,9(5):449~453

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