AT_1受体抗体对大鼠心肌结构和功能的影响  

Effects of angiotensin-1 receptor autoantibodies on the myocardial structure and function of rats

作　　者：金珠[1] 王瑾[2] 张文慧[1] 王小芳[1] 支建明[1] 

机构地区：[1]上海交通大学医学院生理学教研室,上海200025 [2]山西医科大学生理学教研室,太原030001

出　　处：《现代免疫学》2010年第3期202-206,共5页Current Immunology

基　　金：上海交通大学医学院校基金资助项目(05xj21006)

摘　　要：实验观察血管紧张素Ⅱ-1型受体自身抗体(angiotensin type-1 receptor autoantibody,AT_1R-AA)对大鼠心肌结构和功能的影响。选用2月龄健康SD大鼠,用合成的AT_1受体细胞外第二环肽段(165-191)对其进行主动免疫,对照组只用免疫佐剂。ELISA法检测AT_1 R-AA滴度,大鼠尾动脉血压计测量血压和心率;实验结束时进行在体心功能和心脏形态学检测;应用Protein A亲和层析法,从大鼠血清中提取AT_1 R-AA,作用于培养的心肌细胞,用BCA法测定心肌细胞蛋白含量、显微测微器测定心肌细胞直径。结果显示,6周时大鼠免疫组血清中可检测到高滴度的AT_1 R-AA,与对照组相比血压升高,心功能指标中LVSP,+dp/dt max,-dp/dt max均明显增强,左心室与体重比值增加;AT_1 R-AA可使培养的细胞蛋白合成增加、体积增大。提示AT_1 R-AA在体内外均可引起心肌肥大。To observe the effects of angiotensin-1 receptor autoantibodies（AT_1R-AAs）on the myocardial structure and function of rats,healthy SD rats of 2 month age were selected and actively immunized with the extracellular second loop of the cyclopeptide 165-191 fragment of angiotebisionⅡtype-1 receptor in a dosage of 0.5 mg/kg for 12 weeks;while the control rats were immunized only with Freund＇s adjuvant.In the whole course of study,all rats were subjected to be tested for their tail arterial blood pressure and heart rate as well as to be bled to assess the titers of AT_1R-AAs autoantibody by ELISA assay.At the end of experiment,invasive cardiac function and morphology of heart was measured.The AT_1R-AAs were purified by using affinity chromatography with protein A sepharose CL-4B from sera of immunized rats and it was used to act upon on the myocardial cells by addition into media to induce myocardial hypertrophy.The protein content in myocardial cells was determined by BCA assay and the cell diameter were measured with micrometer.It was found that high titers of AT_1R-AAs were found in the sera from immunized rats throughout the period of study in contrast to those from control rats.Blood pressure after 6 weeks appeared to be significantly higher in the immunized rats than those of the control group.Compared with those of control group,the ratio of HW/BW and LVW/BW,the cardiac functioning indexes including LVSP,＋dp/dt max and-dp/dt max increased much more significantly.AT_1R-AAs also increased the overall protein content and the cell diameter of myocardial cells.These results indicate that AT_1R-AAs is intimately involved the process of myocardial hypertrophy both in vitro and in vivo.

关 键 词：主动免疫 抗体 AT_1受体 心功能 心肌结构 

分 类 号：R392.12[医药卫生—免疫学]