M_2和β_1受体抗体与慢性肺源性心脏病关系的实验研究

The experimental study in the role of antibodies against β_1-adrenergic receptor and M_2-muscarinic receptor in the pathogenesis of chronic cor pulmonale

目的用缺氧方法制备的肺源性心脏病(肺心病)大鼠为对象,研究肺心病中M2和β1受体抗体的含量及其与疾病的关系。方法选取健康雄性Wistar大鼠36只,随机分为3组:单纯缺氧组,缺氧加注射FeCl3组,健康对照组。SA-酶联免疫吸附测定(ELISA)法检测血清M2和β1受体抗体变化。最后处死大鼠观察心脏指标,并分析它与抗体滴度的相关性。结果血清中M2和β1受体抗体随缺氧时间延长而升高,滴度分别到第3周达高峰M2受体抗体为1∶80(单纯缺氧组)和1∶53(缺氧加注射FeCl3组),β1受体抗体为1∶60(单纯缺氧组)和1∶45(缺氧加注射FeCl3组),并且P/N值从第2周开始有阳性意义,到第3周同样达高峰M2和β1受体抗体分别为2.88(单纯缺氧组)、2.76(缺氧加注射FeCl3组)和3.25(单纯缺氧组)、3.99(缺氧加注射FeCl3组)。而肺心病大鼠心脏指标最终改变为R/(L+S)0.333±0.027(单纯缺氧组),0.348±0.033(缺氧加注射FeCl3组),R/BW×10-30.58±0.13(单纯缺氧组),0.60±0.15(缺氧加注射FeCl3组),(L+S)/BW×10-32.000±0.024(单纯缺氧组),2.081±0.037(缺氧加注射FeCl3组),并且抗体滴度与心脏改变呈正相关。结论M2和β1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,表明肺心病的发生发展与M2和β1受体的自身抗体密切相关。

Objective To study the antibodies against β1-adrenergic receptor and M2-muscarinic receptor in the rats model of hypoxic chronic cor pulmonale. Methods Experimental animals： 36 Wistar healthy rats of either male weighing 200-300 g were divided randomly into three experimental groups：①Hypoxic group： Single hypoxie group in which the typical model of chronic cor pulmonale was constructed according to the method of XUE＇s.②Hypoxic and injected with FeCl3 group, based on the hypoxic group plus FeCl3 at the same time.③Control group was fed in normal condition. Observed data include detecting the antibodies of β1-adrenergic receptor and M2 receptor by SA-ELISA, cardiac anatomic measurement. Results Cardiac anatomic measurement： the ventricles of both hypoxic group and the hypoxic group plus FeCl3 were weightier[R/（L＋S） 0.333±0.027（hypoxic group）, 0.348±0.033 （hypoxic and injected with FeC13 group）, R/BW×10^-3 0.58±0.13（hypoxic group）,0.60±0.15（hypoxic and injected with FeCl3 group）,（L＋S）/BW×10^-3 2.000±0.024（hypoxic group）,2.081±0.037（hypoxie and injected with FeCl3 group）] than control group. Antibodies of β1-adrenergie receptor and M2-receptor compared by time and quantity, the P/N of hypoxie group was very high after two weeks, and higher along with the weeks ,the peak of hypoxic group was 2.88（M2）,3.25（β1）,and the peak of hypoxie and injected with FeCl3 group ： 2.76（M2）3.99（β1）. Conclusion In hypoxic group, the rate of positive antibody and the titers of antibodies to β1-adrenergic receptor and M2-muscarinic receptor in the sera have been kept with a very high level, which experimentally indicates that there were a great relationship between the antibodies and the pathogenesis of chronic cor pulmonale. The fact that the rate of positive antibody and the titers of antibodies to β1-adrenergie receptor and M2-muscarinic receptor in the sera closely related to the pathological damage in right and left ventricles shows the antibodies to β1-adrenergic receptor and M2-musearinic receptor play a very important role in the development of the pathological alterations in chronic cor pulmonale.