FasL在CVB3心肌炎小鼠心肌浸润细胞中表达及其与心肌病变关系  

EXPERIMENTAL STUDY ON FAS/FASL-MEDIATED CYTOTOXICITY ON THE DEVELOPMENT OF VIRAL MYOCARDITIS

作　　者：熊丁丁[1,2,3] 杨英珍[1,2,3] 胡英[1,2,3] 陈灏珠[1,2,3] 

机构地区：[1]卫生部病毒性心脏病重点实验室 [2]上海市心血管病研究所 [3]上海医科大学中山医院心内科

出　　处：《上海医科大学学报》1998年第3期205-208,共4页Journal of Fudan University(Medical Science)

基　　金：国家九.五攻关项目基金

摘　　要：目的探讨Ｆａｓ／Ｆａｓ配体（ｌｉｇａｎｄ，Ｌ）介导的细胞毒效应在小鼠柯萨奇Ｂ３病毒（ＣＶＢ３）性心肌炎发病中的作用。方法４０只小鼠等分为实验组即ＣＶＢ３感染组及对照组即非感染组；所有小鼠于感染后第１０天处死并取其心脏；采用ＲＴ－ＰＣＲ及免疫组化技术检测心肌浸润细胞中ＦａｓＬ的表达，并用原位杂交方法检测心肌中ＣＶＢ３ＲＮＡ；半定量分析ＦａｓＬ抗原及ＣＶＢ３ＲＮＡ水平，并分析ＦａｓＬ表达水平与心肌中ＣＶＢ３复制及病变程度的关系。结果①实验组存活小鼠心肌均可见单核细胞浸润和坏死等病变，而对照组小鼠心肌均未见任何损害；②实验组存活小鼠心肌中均见ＦａｓＬ抗原阳性细胞浸润，而对照组则无；③ＲＴ－ＰＣＲ检测显示实验组ＦａｓｍＲＮＡ阳性率明显高于对照组（Ｐ＜０．０５）；④ＦａｓＬ抗原阳性信号指数与ＣＶＢ３ＲＮＡ杂交阳性信号指数无显著相关（ｒ＝－０．２５，Ｐ＞０．０５），与心肌病变积分呈显著负相关（ｒ＝０．７２，Ｐ＜０．０５）。结论ＣＶＢ３心肌炎小鼠心肌浸润细胞可表达ＦａｓＬ；Ｆａｓ／ＦａｓＬ介导的细胞毒效应可能无抗病毒作用，但可能通过调节细胞介导的细胞毒作用对心肌细胞起一定的保护作用。PURPOSE To clarify the effect of Fas/FasL-mediated cytotoxicity on the development of murine acute myocarditis caused by coxsackievirus B3 (CVB3). METHODS Forty mice were equally divided into an experimental group (CVB3-infected mice) and a control group (non infected mice). The mice were killed and the hearts were removed on day 10 after infection. The expression of FasL in the infiltrated cells of the myocardium was determined by immunohistochemistry and RT-PCR technique. CVB3-RNA in the myocardium was detected by in situ hybridization. In addition, the levels of FasL antigen and CVB3 RNA were semiquantatively analyzed, and the relationship between the FasL expression level and the degrees of CVB3 replication and myocardial lesions was investigated. RESULTS (1)Myocardial lesion such as mononuclear cell infiltration and necrosis developed in all the survival mice of the experimental group ( n=10 ), however, no myocardial lesion was found in control group; (2) FasL positive infiltrating cells were found in all the survival mice of the experimental group, but none was detected in the control group; (3) RT-PCR showed that the positive ratio of FasL mRNA is significantly higher in the experimental group than that in the control group ( P <0.05); (4)The index of FasL antigen positive signal didnot show significantly correlation with that of the CVB3 RNA positive signal ( r=-0.25, P>0.05 ) but had significant negative correlation with myocardial histopathological score ( r=-0.72, P<0.05 ). CONCLUSIONS FasL was able to express in the infiltrating cells of the myocardium in the mice with myo￣carditis caused by CVB3; Fas/FasL-mediated cytotoxicity had no direct influence in limiting virus replication, but might have protective effect on myocardium by regulating cell mediated cytotoxicity.

关 键 词：病毒性心肌炎 CMC FAS/FASL 小鼠 CVB3 

分 类 号：R542.210.2[医药卫生—心血管疾病] R373.23[医药卫生—内科学]