Lewis大鼠急慢性期风湿性心脏炎模型的比较
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国家自然科学基金(81260067)。


A comparative study of different animal model of acute and chronic rheumatic carditis in Lewis rats
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    摘要:

    目的 比较3种急慢性期风湿性心脏炎模型,找出理想的动物模型。 方法 抗原Ⅰ、Ⅱ分别为灭活溶血性链球菌(GAS)与完全弗氏佐剂(CFA)、不完全弗氏佐剂(IFA)混合的乳化剂。 Lewis雌鼠随机分成四组:实验A、B、C组首次后足垫注射0.2 mL抗原Ⅰ,随后分别注射抗原Ⅰ、Ⅱ、未灭活GAS免疫刺激建立模型,对照组D组分别对应ABC组各6只,GAS替换为生理盐水免疫刺激。于第7、12、24周末处死每组各6只,行血液生化及心脏HE染色检查。 结果 C组死亡率25%;A组心脏炎发生率最高,12周A、C组急性期损伤心肌、瓣膜弥漫性炎症细胞浸润,心肌间质风湿细胞聚集,较B组明显;24周慢性期损伤A组瓣膜纤维化程度及比率较B、C组高;D组心肌、瓣膜均无病理改变。 结论 A组CFA与GAS1:1混合乳化剂免疫大鼠5次,之后GAS连续刺激,能为急慢性期风湿性心脏病的实验研究提供较好的可复制的动物模型。

    Abstract:

    Objective To make comparisons of the three models of acute and chronic rheumatic carditis to find out an optimal animal model. Methods AntigenⅠwas a emulsifier mixed by complete freund's adjuvant(CFA) and Group A streptococcus(GAS). AntigenⅡ was mixed by incomplete freund's adjuvant(IFA) and GAS. Female Lewis rats were randomly divided into four groups: A, B, C treatmeat groups were immuned with antigenⅠat the foot pad firstly. Subsequently, rats in group A、B、C were injected antigenⅠ, antigenⅡand activated GAS respectively to make the models of RHD. Rats in control group D were immunized with the same protocol outlined as treatment groups but without GAS. Respectively 7, 12, 24 weeks the rats were sacrificed 24(each group was 6). The blood biochemical item and Hematoxylin-eosin(HE) staining of hearts were detected. Results In group C the mortality was 25%. In group A, the incidence of carditis was the highest. Histopathological manifestations of group A, C was not only revealed acute damage such as inflammatory cell infiltrate as well as group B, but also the Aschofflike cells in the myocardial cells interstitial. But in group A and C there had a great degree of the inflammatory cells infiltration than group B. At 24th week rats in group A detected the rate and degree of valve fibrosis in chronic damage were higher than group B and C. None of rats in group D presented carditis or valvulitis. Conclusion In group A, giving the GAS with continuous stimulation after using the mixed emulsification of CFA and GAS to immune Lewis rats for five times was a appropriate method which could provide an optimal animal model for experimental study of acute and chronic rheumatic heart disease.

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李文婷,曾志羽,桂春,郑慧蕾,李靖,韦恒,文宏,黄伟强. Lewis大鼠急慢性期风湿性心脏炎模型的比较[J].中国比较医学杂志,2015,25(7):30~33.

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