An experiment model of cardiomyopathy was crea ted by immunizing rats for 18 months with synthetic peptides corresponding to th e sequence of the second extracellular loop of both β1-adrenoceptor or M2 -muscarinic receptor. Ninety rats were used and divided into three groups: a co ntrol group (n=30), a group immunized with the peptide corresponding to the (β1-adrenoceptor (β1 group, n=30) and a group immunized with the pept ide corresponding to the M2-muscarinic receptor (M2 group, n=30). To de termine if there was a defect of immune regulation in rats of three groups, the percentage of total T cell (CD3＋), helper/induce T cells (CD4＋) and suppre ssor/cytotoxic T cells (CD8＋) were measured. In the sera from both groups of immunized rats, high-titer of anti-peptide antibodies were found throughout th e study period, but only a low titers of antibodies were found in the sera from some control rats or in the preimmu ne sera of some immunized rats. The ratio of CD4＋/CD8＋ T-cells were signi ficantly higher in both immunized groups than that in the control group after 7 days to 3 month of immunization. The myocardial receptor density of both immuniz ed groups displ ayed a strong trend toward receptor up-regulation after 12 months of immunizati on, but down-regulation during 18 month. Both groups of immunized rats displaye d significantly enlarged ventricles and thinner walls compared with the control. However, in contrast to the β1 group, which showed enlarged cavities in bot h left and right ventricles, the M2 group was mainly affected in the right ventr icles. Moreover, morphological examination of the hearts of rats from immunized groups demonstrated significant alterations such as focal myofibrillar lysis, lo ss of normal myofilament banding pattern with hypercontraction bands, mitochondr ial swelling and condensation, sarcoplasmic vacuolation and deposition of dense granules in both the sarcoplasm and myofibrils. No obvious alterations were note d in the co ntrol rats. Eighteen months after immunization, the left ventricular systolic an d diastolic function in both of immunized groups were remarkably lowered than th at of in the control group. These results suggested that immunization by peptide , corresponding to the target sequences for anti-receptor autoantibodies in idi opathic dilated cardiomyopathy, induces morphological and functional changed in the heart similar to those found in the human heart diseases.%用合成的β1-受体功能表位肽段以及M 2受体功 能表位肽段肽连续18个月免疫大鼠，结果发现：①外周血T淋巴细胞亚群的改变：T细胞亚群 测定结果发现，在两免疫组免疫24 h后CD4+/CD8+即开始升高，到第7 d时达到一个较高 的水平，3个月时开始下降但仍高于同期对照组，第9个月时降至对照组水平，18个月时明显 降低；对照组的CD4+/CD8+也表现为处理24 h后升高，但从第3 d时开始下降，到第7 d 时 与处理前水平相同；②β1-受体肽段和M2受体肽段免疫大鼠18个月心功能的改变：免 疫6、12、18个月后测定心功能显示，免疫组dp/dtmax及-dp/dtmax呈先升高 后降低的趋势， 而对照组则无变化；③β1-受体和M2受体密度与亲和力的改变；与对照组相比，两免 疫组模型受体密度在第6和第12个月时呈上调的趋势，在18个月时下调；而受体与特异性放 射配体的亲和力在12个月以前变化不明显，但在18个月时则明显降低；④心脏体视学指标的 改变；与对照组相比，免疫组大鼠心脏增重；β1组左室腔和右室腔明显增大，左右室 壁变薄；M2组则表现出明显的右室腔变大和右室壁变薄，而左室累及较轻；⑤心肌组织光 学显微镜下的变化；两免疫组模型存在有灶状心肌细胞变性、坏死、坏死局部有炎性细胞 浸 润。⑥心肌细胞电镜变化特点：电镜下，两免疫组心肌细胞内有灶状肌原纤维溶解、肌丝丢 失、线粒体肿胀和浓缩、肌浆空泡形成等变化，但两组的变化特点不同。β1组的变化主 要为先肌原纤维的溶解，线粒体的改变趋势为先增生，在12个月以后变性才渐明显；而M 2组的改变主要为先累及线粒体后影响肌原纤维。结论：以上结果提示，采用与人β1 和 M2受体细胞外第二环表位肽段序列相一致的合成肽段免疫大鼠，可引起机体免疫系统调 节失衡，并诱导出与人类心肌疾病相类似的心脏形态学和功能学的改变。
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