2型糖尿病大鼠心肌转化生长因子β1表达与马来酸罗格列酮干预的影响

Expression of transforming growth factor beta 1 in myocardium of rats with type 2 diabetes associated with the Avandia treatment

目的:观察马来酸罗格列酮对2型糖尿病大鼠心肌转化生长因子β1表达的影响。方法:实验于2004-12/2005-06在同济医学院附属协和医院心血管研究所实验室进行。取42只Wistar大鼠以高热量饮食喂养1个月后(体质量约230g)单纯随机分为:正常组(n=6)、马来酸罗格列酮组(n=12)、格列齐特组(n=12)及糖尿病未治疗组(n=12)。后3组大鼠以33.3mg/kg链脲佐菌素腹腔一次性注射建立实验性2型糖尿病大鼠模型。造模成功后马来酸罗格列酮组大鼠给予马来酸罗格列酮片2mg/kg,格列齐特组给予格列齐特25mg/kg,均为灌胃给药,1次/d,其他2组不干预。造模后所有大鼠为普通饮食喂养,给药12周后断颈处死大鼠。应用投射电镜评价各组心肌重构情况,并应用免疫组化方法和反转录-聚合酶链反应方法分别检测心肌转化生长因子β1蛋白和mRNA表达水平。结果:33只大鼠进入结果分析。①糖尿病模型大鼠心肌均存在明显的心肌重构,但马来酸罗格列酮组病变较轻。②心肌转化生长因子β1蛋白和mRNA水平:马来酸罗格列酮组、格列齐特组及糖尿病未治疗组明显高于正常组(P<0.01,0.05),马来酸罗格列酮组明显低于糖尿病未治疗组(P<0.05)。结论:马来酸罗格列酮能够明显改善糖尿病大鼠早期心肌重构,机制可能与抑制心肌转化生长因子β1的表达有关。

AIM： To estimate the effect of Rosiglitazone （Avandia） on expression of transforming growth factor β1 （TGFβ1） in myocardium of rats with type 2 diabetes. METHODS： The experiment was conducted at the laboratory of the Institute of Cardiovascular Disease of Tongji Medical College from December 2004 to June 2005. Forty-two adult female Wistar rats were fed with high caloric diet, and one month later （their body mass were about 230 g） they were randomly divided into normal control group （n=6）, Avandia group （n=12）, Gliclazide group （n=12） and diabetes group （n=12）. The rats of the latter three groups were intraperitoneally injected with 33.3 mg/kg streptozotocin to establish the rat models of type 2 diabetes. Then the rats in the Avandia group were given 2 mg/kg Avandia, the rats in the Gliclazide group were given 25 mg/kg Gliclazide, once daily, the other two groups were not given any intervention. All the rats were fed with normal diet and killed after 12 weeks of administration. The myocardial recombinant of each group was estimated by projectoscope, and myocardium TGFβ1 protein and mRNA were measured by immunohistochemistry staining and RT-PCR, respectively. RESULTS： A total of 33 rats were involved in the result analysis.①There was obvious myocardial reconstitution in the rat models of diabetes, but the Avandia group was lighter. ②TGFβ1 protein and mRNA： The Avandia group, Gliclazide group and diabetes group were significantly higher than that of the normal group （P 〈 0.01, 0.05）, and the Gliclazide group was obviously lower than the diabetes group （P 〈 0.05）. CONCLUSION： Avandia can improve the myocardial reconstitution in rat models of diabetes, which is related to the inhibition of the expression of TGFβ1.