大鼠肾性高血压与心脏受体自身抗体产生的关系

Relation of renal hypertension to the genesis of cadiac receptor autoantibodies in rats

目的 通过建立肾动脉狭窄 (2K1C)所致的高血压大鼠模型 ,观察高血压形成过程中 ,血清中抗心脏 β1肾上腺素能受体和M2 胆碱能受体自身抗体的生成及变化规律 ,同时检测机体免疫功能的变化 ,研究二者之间的关系。方法 将健康Wis tar大鼠随机分为两组 ,对实验组大鼠施两肾一夹型肾动脉狭窄手术 ,建立肾性高血压模型。以SA -ELISA法检测血清中自身抗体的滴度水平 ,流式细胞仪检测血中淋巴细胞亚群CD4+ /CD8+ 的比值。利用MS30 2软件测定左室压及左室最大收缩速率和最大舒张速率 ,乳鼠心肌细胞培养检测自身抗体的生物学活性。结果 实验组大鼠在术后 3d即出现血压的升高 ,两周时基本稳定。术后 2周 ,血清中抗心脏 β1肾上腺素能受体和M2 胆碱能受体自身抗体的阳性率分别由术前的 16 .39%和11 48%上升为 6 6 .6 7%和 72 .2 2 % (P <0 .0 0 5 ) ,同时出现血清中自身抗体滴度水平的增高 ,分别较术前的 1∶(6 9.6 4± 1.5 5 )和 1∶(44 .16± 2 .0 9)有显著升高 ,以后抗体滴度继续升高 ,第 6周达峰值 ,分别为 1∶(141.5 8± 1.84)和 1∶(172 .44± 1.37) ,阳性率基本维持不变 ,第 8周起 ,抗体滴度开始下降 ,术后 13周 ,基本回到术前水平。而伪手术组抗体滴度及阳性率与术前相比 ,均无明显变化。免疫功能测定显?

Objective In rat's renal hypertension model, the genesis of anti cardiac β 1 adrenoceptor and M 2 muscarinic receptor autoantibodies and their changes during the development of renal hypertension were studied. Changes in immunological function were simultaneously examined and made a correlation analysis with the changes in autoantibodies. Methods Healthy Wistar rats were divided into two groups: experimental group and control group.Renal hypertension model (2K1C) was set up by clipping the left renal artery. Serum autoantibodies were detected by using SA-ELISA assay. Lymphcyte subsets CD4 +/CD8 + were tested using flow cytometer. LVESP,LVEDP and ±dp/dtmax were measured by MS302 program on computer. Biological functions of autoantibodies were tested by adding autoantibodies to the cultured neonatal cardiomyocytes. Results Blood pressure began to rise at d 3 after clipping and attained at a stable higher level after two weeks. By this time the frequency of anti β 1 and M 2 receptor autoantibodies were increased from the control of 16.39% and 11.48% to the 66.67% and 72.22%, respectively ( P <0.005). The antibody titers were increased from the control of 1∶(69.64±1.55) ( P <0.05) and 1∶(44.16±2.09) ( P <0.005) to 1∶(119.8±1.90) and 1∶(136.48±2.26), respectively. Antibody titers increased to peak value at week 6; however, they began to decrease gradually and returned to the pre clipping level at week 13. There were no significant changes in the frequencies and titers in both sham operated group and healthy control. Ratio of CD4 +/CD8 + increased significantly at week 2 after clipping and attained the peak at week 6. Ratios of CD4 +/CD8 + are correlated well with antibody titers. Ratio of CD4 +/CD8 + in sham operated group showed no significant changes as compared with control group. After addition of positive sera to cultured beating cardiomyocytes, they modified beating frequencies of neonatal heart, showing an agonist like activity. Conclusion ① During the early period of renal hypertension, the frequency and titer of autoantibodies in sera of rats with renal hypertension rised significantly. Autoantibodies generated in response to renal hypertension underwent automatically wax and wane process. ② During the early period of the development, immunological function was also changed accompanying with the genesis of autoantibodies, suggesting the involvement of autoimmune mechanism during the development of renal hypertension. ③ In considering the agonist like effects of antibodies, it is suggested that in renal hypertension, autoantibodies might be one of the causes leading to cardiac dysfunction.