G蛋白偶联AT1和β1受体抗体早期预测2型糖尿病伴冠心病患者死亡危险性分析

Study on the relevant factors of the autoantibodies against β1-receptor and AT1-receptor predicts death risk from coronary heart disease in elderly patients with type 2 diabetes mellitus

目的研究血清抗血管紧张素Ⅱ1型受体自身抗体（AT1R—Ab）和B1肾上腺素能受体自身抗体（β1R—Ab）与老年2型糖尿病伴冠心病患者死亡危险性的关系。方法随机选择2001年1月至2007年1月广州军区武汉总医院内分泌科及华中科技大学附属协和医院心内科收治的老年2型糖尿病伴冠心病患者137例，进行了3—11年的追踪研究，老年2型糖尿病不伴冠心病137例作对照。以合成的B1R和AT1R多肽片段为抗原，应用酶联免疫吸附测定（ELISA）技术，检测上述患者血清中B1R—Ab和AT1R-Ab。采用Kap-lan-Meier生存曲线计算死亡率。结果（1）2型糖尿病伴冠心病血清β1R-Ab阳性率（41．7％）和AT1R-Ab阳性率（43．7％）明显高于2型糖尿病不伴冠心病组（17．5％和19．7％），两组比较差异具有统计学意义（P〈0．01）；（2）2型糖尿病伴冠心病患者同一个体β1R-Ab和AT1R—Ab双阳性率为30．7％（42／137），明显高于不伴冠心病组的9．5％（11／137），两组比较差异具有统计学意义（P〈0．01）；（3）2型糖尿病伴冠心病组AT1R-Ab阳性组死亡率51．7％（31／60），明显高于受体抗体阴性组的9．1％（7／77），两组比较差异具有统计学意义（P〈0．01）。结论β1R-Ab和AT1R—Ab可能参与老年2型糖尿病伴冠心病患者的发病，并且是导致老年2型糖尿病伴冠心病患者死亡危险性增高的主要原因之一。

Objective To investigate the relationship between autoantibodies against β1 adrenergic receptors （β1R-Ab）, angiotensin Ⅱ type 1 receptors（ AT1 R-Ab）and the death risk of elderly type 2 diabetic patients with coronary artery disease （ CAD ）. Methods 137 elderly type 2 diabetic patients with CAD were selected toperform a 3-11 year-follow-up study. In this study, from department of endocrinology in Wuhan General Hospital of Guangzhou Military Command and department of cardiology in Wuhan Union Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology from January 2001 to January 2007, the epitopes of the second extracellular loop of β1-receptor（197-222） and ATl-receptor（ 165-191 ）were synthesized and used as antigen to screen the serum autoantibodies by enzyme-linked immunosobent assay（ELISA）. Mortality rates were derived from Kaplan-Meier survival curves. Results （1） In dderly type 2 diabetic patients with CAD, the positive rates of β1R- Ab and AT1R-Ab were significantly higher than those the positive rates of the autoantibodies against β1-receptor. And the positive rates of AT1R-Ab and β1R-Ab were 43.7% vs. 17.5% ,41.7% vs. 19. 7%, respectively, both P 〈 0. 01. There was significant statistics of difference. （2） In elderly type 2 diabetic patients with CAD the positive rates of β1R-Ab and AT1R-Ab was 30. 7% （31/137）which was significantly higher than those without CAD patients,the positive rates of 131R-Ab and AT1R-Ab was 9.5% （11/137） （ P 〈 0. 01 ）. （ 3 ） The CAD death rate in the disease group positive of ATIR-Ab was 51.7% （31/60） which was significantly higher than the negative group of AT1R-Ab 9. 1% （7/77）. Conclusion The positive rates of the β1R-Ab and AT1R-Ab relates to the risk of CAD death in elderly patients with type 2 diabetes mellitus, and suggest that these β1R-Ab and AT1R-Ab may play important roles in the pathogenesis of the type 2 diabetes with CAD.