M_2受体抗体在肺心病发病中的作用及其机制的实验研究

Antibodies Against M2-muscarinic Receptor and Chronic Cor Pulmonale in Rats

目的通过各模型组动物抗体的阳性率、滴度和肺动脉压改变分别与各观测指标的相关性研究,及左右心室病变程度的相关性研究,分析肺心病发病与抗M2受体抗体的关系。方法选取健康雄性Wistar大鼠60只,随机分为5组(正常对照组、单纯缺氧组、环孢菌素A组、尼卡地平组、主动免疫组)。SA-酶联免疫吸附法检测血清中M2受体抗体含量。采用孙氏法测定肺动脉压。结果 M2受体抗体测定,单纯缺氧组为66.67%,主动免疫组为100.00%,与对照组(阳性率为8.33%)比较均有统计学意义(P<0.01)。环孢菌素A组与对照组比较无统计学意义。肺动脉压测定,单纯缺氧组及环孢菌素A组明显高于正常组。免疫组、尼卡地平组与正常组没有明显差异。与对照组比较,单纯缺氧组及主动免疫组心脏结构有明显变化。右室/体重比(R/BW);左室/体重比(L/BW);左室加室间隔(L+S);右室/左室加室间隔重量比[R/(L+S)]与对照比较均有统计学意义(P<0.05)。环孢菌素A组与对照组比较无统计学意义。结论 M2受体抗体阳性率及抗体滴度在大鼠肺心病模型中明显增高,表明肺心病发病与对M2受体的自身免疫密切相关。大鼠左右心脏病理改变与M2受体抗体阳性率及抗体滴度高度相关,而与肺动脉增高相关性不高;提示M2受体抗体对肺心病心脏病变的发生与发展具有重要作用。

Objective To study the effect of autoantibodies against cardiac M2-muscarinic acetylcholine receptor on chronic cor pulmonale.Methods Sixty Wistar healthy rats were divided randomly into five experimental groups（n=12 in each group）：Control group fed in normal condition,hypoxic group,cyclosporin A group,nicardipine group,and immunized group with M2-muscarinic receptor peptide immunized group.The rate of positive of autoantibody and titer of antiserum were tested by ELISA.Results In both hypoxic group and immunization group,the rate of positive of autoantibody and the titer of autoantibodies to M2-muscarinic receptor in the sera rose to a very high level.The rates of positive sera were 66.67% and 100.00% in hypoxic group and immunized group,respectively.The geometric means of the anti-M2-receptor antibody titers in hypoxic group and immunization group were 1∶85 and 1∶152,respectively.In cyclosporin A group and nicardipine group,the rate of positive autoantibody in the sera was lower than that in hypoxic group.The pulmonary artery pressure in hypoxic group and cyclosporin A group were higher than those in control group.Pulmonary artery pressure in nicardipine group and immunized group showed no difference compared with the control group.There was no difference in light microscopic findings in cyclosporin A group and control group.Both the left and right ventricles were significantly enlarged in terms of cavity dimension in hypoxic group and immunization group（P0.05）.There was no significant difference in the cavity dimension of left and ventricle between cyclosporin A group and the control group.Conclusion The rate of positive antibody and the titers of antibodies against M2-muscarinic receptor in the sera keep with a very high level in hypoxic group,which indicates that there are some relationship between the antibodies against M2-muscarinic receptor and the chronic cor pulmonale.The fact that the rate of positive antibody and the titers of antibodies against M2-muscarinic receptor in the sera closely related to the pathological damage in right and left ventricles but to pulmonary hypertension suggests that the antibodies to M2-muscarinic receptor play a very important role in the development of the pathological alterations in chronic cor pulmonale.