小剂量环孢素A联用细胞毒T淋巴细胞A4-Ig治疗器官移植排斥反应

目的　研究小剂量环孢素A(CsA)联用细胞毒T淋巴细胞A4 Ig(CTLA4 Ig)治疗器官移植排斥反应的效果。　方法　采用Ono′s方法建立大鼠心脏移植排斥反应动物模型 ,将实验动物分为 4组。A组 :对照组 ,未给予任何治疗 ;B组 :腹腔内注射CsA ,10mg·kg-1·d-1,连续 7d ;C组 :术后第 2天 1次性注射CTLA4 Ig 10 0 μg ;D组 :术后 1～ 7d连续腹腔内注射CsA ,2mg .kg-1.d-1,术后第 2天加用CTLA4 Ig 5 0 μg。观察移植心脏存活天数及术后IL 2含量和组织学变化。　 结果　A、B、C、D 4组大鼠移植心脏存活时间分别为 ( 7 2± 0 7)、( 19 4± 2 1)、( 3 1 6± 1 8)和 ( 2 4 6± 2 1)d ,与对照组相比 ,各治疗组大鼠心脏存活时间明显延长 ,差异有显著性意义 (q =3 2 7 83 ,P <0 0 5 ) ,D组与C组相比差异无显著性意义 (q =1 86,P >0 0 5 ) ;各治疗组术后IL 2含量明显减低 ,与对照组相比差异有非常显著性意义 (q=9 82 ,P <0 0 1) ;A、B、C和D组排斥反应分级分别为Ⅳ、Ⅲ、Ⅰ和Ⅰ级。　结论　CTLA4 Ig抗排斥反应能力比CsA强 ,小剂量CsA联合使用CTLA4 Ig能增强治疗排斥反应疗效 ,两者具有正协同作用。

Treatment of organ transplant rejection with low doses of CsA and CTLA4-Ig

OBJECTIVE: To study on treating organ transplant rejection with low doses of CsA and CTLA4-Ig. METHODS: We set up a rat's cardiac transplant rejection model by Ono's way. The experimental rats were divided into four groups: group A: without any treatment; group B: intraperitoneal injection of CsA at 10 mg / (-1) / (-1) 1 - 7 days; after operation group C: intraperitoneal injection of 100 microgram CTLA4-Ig after 2nd operative day; group D: intraperitoneal injection of CsA 2 mg / (-1) / (-1) 1- 7 days after operation. 50 microgram CTLA4-Ig was given intraperitoneally on the 2nd day postoperation. The survival days of allograft, serum concentration of IL-2, and histological changes were tested. RESULTS: The allograft survival time of the four groups was 7.2 +/- 0.7 (group A), 19.4 +/- 2.07 (group B), 31.6 +/- 1.8 (group C) and 24.6 +/- 2.07 (group D) respectively. There were significantly differences among the groups (P < 0.05). The survival time in group D was more prolonged than that in group B (P < 0.05). The concentration of IL-2 was significantly decreased after operation. Significant difference was observed between the control group and each treated group (P < 0.01). In group A, B, C and D allograft rejection was graded IV, II, I and I respectively. CONCLUSION: CTLA4-Ig had a stronger immunosuppression than did CsA. The low doses of CsA and CTLA4-Ig had show a synergistic immunosuppression in allograft transplantation.