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大鼠同种异体心脏移植中细胞间粘附分子-1表达及环孢嘌呤A的作用
EXPRESSION OF INTERCELLULAR ADHESION MOLECULE-1 IN THE CARDIAC ALLOGRAFTS AND THE EFFECT OF CYCLOSPORIN A
【摘要】 目的 研究大鼠同种异体心脏移植模型中细胞间粘附分子-1(ICA-1)的表达以及环抱嘌呤A(CsA)抗免疫排斥的作用,井探讨该作用的影响因素。方法 根据国际心肺移植组织(ISHLT)1990年心脏急性排异反应分级标准.对心脏移植大鼠进行排异反应分析;用免疫组织化学方法检测ICAM-l的表达部位和表达水平。结果 心脏移植后,供者心脏和主动脉标本中,1d和 3d时出现轻度炎性浸润,排异反应为 1A或 1B级;11d和 12d时可出现弥谩性炎性浸润和心肌坏死,并伴明显水肿、出血以及血管炎.排斥级别达3B或4级。CSA治疗可使心脏移植排异降低1~2.5级。移植后血管内皮细胞、外膜浸润淋巴细胞的ICAM-1表达显著升高。CsA治疗可明显抑制供者心脏及主动脉的ICAM-1表达。该抑制作用在l~3d内,呈CsA剂量依赖性.而在7~11d内无剂量差异。结论CsA治疗是下凋淋巴细胞迁移和浸润、减弱移植排斥反应的有效手段.其机理可能与降低粘附分子表达有关。
【Abstract】 Objective To study the expression of intercellular adhesion molecule-1 (ICAM-1 ) in the rat cardiac heterotopic allo- grafts and the effect of cyclosporin A on prevention of allograft rejection. Methods Heart transplantated animals were divided into three groups: Group Ⅰ(control), Group Ⅱ(CsA 7. 5mg/kg B W, daily) and Group Ⅲ(CsA l5mg/kg B W, daily). Acute cardiac rejection grade was valued by the standrd of ISHLT(1990 ). Immunohistochemistry was performed to analyze the expression of ICAM-1 in heart grafts and donor aorta segments. Results After heart transplantation, it was found that from day 1 to 3, there was sligtly inflammatory infiltratiation, the rejection was graded 1A of 1B, But from day 11 to 12, there were disseminated inflammation and cardiac necrosis with serous hyperemia, exutation, edema, acute vasculitis and myocarditis. The rejection grade was 3B or 4, and could be reduced 1to 2. 5 grades by administration of CsA. It was also found that both in heart graft and donor aorta segments the expression of ICAM-1 on the endothelium cells, infiltrated lymphocytes was clearly increased. It was time-dependent and could be down-regulated by administra- tion of CsA. On Day 1 and Day 3 the suppressing function of CsA on expressing of ICAM-1 showed singificant dosage-dependent. But from Day 7 to Day 11, it appeared dosage- independent. Conclusiou Trea tment with CsA is an effect ive methed to down- regulate I - CAM-1 expression and could reduce the lympphocyte migration and filtration. These results may explain, in part, the mechanism of CsA reducing acute rejection in a rat cardiac transplantation medel.
【Key words】 Intercellular adhesion molecular-l; Cyclosporine A; Heart transplantation; Immunohistochemistry;
- 【文献出处】 解剖学报 ,Acta Anatomica Sinica , 编辑部邮箱 ,2000年S1期
- 【分类号】R392.4
- 【被引频次】1
- 【下载频次】36