抗α1肾上腺素能受体自身抗体对糖尿病大鼠心肌TGF-β1和smads2/3表达的影响  

Effect of autoantibodies against α1-adrenergic receptor on the expression of transforming growth factor-β1 and smads2/3 in the myocardium of diabetic rats

作　　者：谭学莹[1,2] 赵林双[1] 白伟伟[1,2] 李德忠[3] 王敏[4] 

机构地区：[1]广州军区武汉总医院内分泌科,430070 [2]南方医科大学 [3]广州军区武汉总医院医学实验科,430070 [4]华中科技大学同济医学院心血管病研究所

出　　处：《中华临床医师杂志（电子版）》2013年第2期115-118,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：湖北省卫生厅课题(2010-820JX5C18)

摘　　要：目的探讨抗α1-肾上腺素能受体自身抗体(抗α1-R抗体)对糖尿病(DM)大鼠心肌损害的作用机制。方法 (1)以抗α1-R抗体阳性的DM大鼠(抗体阳性组)为模型,设立抗α1-R抗体阴性DM大鼠(抗体阴性组)、正常Wistar大鼠(健康对照组)为对照。(2)用酶联免疫吸附试验法检测抗α1-R抗体。(3)用电子天秤称体重。(4)用免疫组织化学方法检测左心室心肌组织的TGF-β1和smads2/3的表达,并在光镜下观察心脏病理变化,计算平均光密度值(MOD)。(5)在电镜下观察心脏超微结构的改变。结果 (1)实验结束时,DM抗体阳性组和抗体阴性组大鼠体重均明显低于实验前(均P<0.01),健康对照组大鼠体重明显高于实验前(P<0.01)。(2)TGF-β1和smads2/3在抗体阳性组DM大鼠心肌组织中过度表达,MOD值明显高于抗体阴性组和健康对照组(分别P<0.05,P<0.01)。(3)心肌超微结构显示DM大鼠心肌纤维变性坏死,肌原纤维之间糖原减少,肌质网肿胀、扩张,线粒体大小悬殊,或肿胀或萎缩,微血管基底膜轻度增厚,其中抗体阳性组损伤更严重;健康对照组未见明显异常。结论抗α1-R抗体可影响DM大鼠心肌组织的TGF-β1和smads2/3的表达,并且可能通过增加促纤维化生长因子TGF-β1的表达导致DM大鼠心肌损害的进展、加重。Objective To study the pathogenesis of autoantibodies against α1-adrenergic receptors （α1R- Ab） on eardiomyopathy of diabetic rats. Methods （1）α1R-Ab positive diabetic rats were used as model（ ctlR-Ab positive group）,with α1R-Ab negative diabetic rats （α1R-Ab negative group）and normal Wistar rats （normal group）of the same age as controls. （2） The epitopes of the second exlracellular loop of otl-receptor was synthesized and used as antigens to detect the α1-receptor by ELISA. （ 3 ） Weight was measured by electronic balance. （4） Expression of TGF-β1 and smads2/3 in myocardium of left ventricle were detected by immunohistochemical staining, and calculated the value of MOD. （5）Pathological changes in the myocardium were observed by light microscope and electron microscope. Results （ 1 ） At the end of this experiment, the weight in α1 R-Ab positive group and negative group were lower than before （both P 〈 0.01 ）, but normal group was higher than before（ P 〈 0.01 ） ;（2）In α1R-Ab positive group, the expression of TGF-β1 and smads2/3 were higher than ot1 R-Ab negative group and normal group （respectively,P 〈 0.05, P 〈 0. 01 ）;（3 ）Myocardial pathological changes in αR-Ab positive group were the most serious,mitochondrial reduce, arrangement disorder, show vacuolar degeneration, interstitial collagen hyperplasia, microvascular basement membrane thickening. There was on obviously abnormal in normal group. Conclusions The αlR-Ab could effect the expression of TGF-β1 and smads2/3 in the myocardium of diabetic rats,resulting in the aggravate of cardiomyopathy through increasing the expression of TGF-β1.

关 键 词：受体 肾上腺素能Α1 自身抗体 糖尿病 心肌疾病 转化生长因子Β1 

分 类 号：R587.2[医药卫生—内分泌]