摘要
目的探讨雷帕霉索对肝移植大鼠皮下移植瘤生长的影响。方法建立大鼠肝移植模型后实验分为五组，Ⅰ组：以Wistar大鼠作为供体，SD大鼠作为受体，术后不接受任何治疗作为急性排斥对照组。Ⅱ组：以SD大鼠作为供体及受体，术后3d在左肩胛区皮下接种腹水瘤Wlaker-256细胞，生理盐水灌胃作为皮下肿瘤生长的对照组。Ⅲ、Ⅳ、Ⅴ组：均以Wistar大鼠作为供体，SD大鼠作为受体，术后分别服用环孢素（每日20mg／kg体重，灌胃）、他克莫司（每日1mg／kg体重，灌胃）和雷帕霉素（每日1mg／kg体重，灌胃），术后3d在左肩胛区皮下接种腹水瘤Wlaker-256细胞。每周3次记录Ⅱ-Ⅴ组受体大鼠皮下肿瘤生长情况，绘制成瘤曲线；并于皮下接种肿瘤后14d处死大鼠，检测受体大鼠的肝功能、移植肝病理及皮下肿瘤大小。结果与急性排斥大鼠（Ⅰ组）比较，接受免疫抑制剂治疗的各组受体大鼠（Ⅲ～Ⅴ组）均未出现严重的急性排斥反应；同时，与生理盐水灌胃的同基因肝移植术后皮下荷瘤大鼠（Ⅱ组）比较，雷帕霉素明显抑制了大鼠皮下肿瘤的生长[（1．41±0．87）与（3．65±0．87）cm^3，P〈0．05]，环孢素及他克奠司则促进了皮下肿瘤的生长[（9．56±2．81）与（3．65±0．87）cm^3，P〈0．01；（8．11±1．69）与（3．65±0．87）cm^3，P〈0．01]。结论雷帕霉素在有效保护移植物的同时抑制了移植受体体内肿瘤的生长；环孢素和他克莫司抑制了机体的排斥反应，但也同时促进了受体体内肿瘤的生长。
Objective To investigate the effects of rapamycin on the growth of subcutaneously transplanted tumors in rats. Methods In the tumor-transplant model, SD rats received subcutaneous syngenie walker-256 carcinosareoma cells 3 days after orthotopic liver transplantation （Wistar-to-SD） with character of acute rejection. Rapamycin （ 1 mg/kg every day） , FK506 （ 1 mg/kg every day） or cyelosporine （20 mg/kg every day） was initiated with transplantation. The transplantation models （Wistar-to-SD） received no treatment as rejection control group. Another syngenic transplantation group （SD-to-SD） receiving walker-256 with saline served as tumor control group. The tumor volume in the treatment and control groups was evaluated three times every one week. The clinical characters, the liver function, and the transplantated liver pathologic character were observed and measured on tumor postimplantative day 14. Results Compared with the rejection control group, the function of graft was improved, and the rejection reaction inhibited in the immunosuppressive treatment groups. The raparnycin treatment group showed a significant decrease of tumor volume [ （ 1.41 ± 0. 87 ） vs （3.65 ± 0.87） cm^3 , P 〈 0.05 ], and cyclosporine or FK506 group increased tumor size versus the tumor control group [ （9.56 ± 2.81 ） vs （3.65± 0.87） cm^3 ,P 〈 0. 01 ; （ 8.11 ± 1.69） vs （ 3.65 ± 0.87） cm^3, P 〈 0.01 ] at the end of treatment. Conclusion Rapamycin simultaneously protects allografts from rejection and inhibits tumor growth in a complex transplant-tumor situation. Notably, cyclosporine or FK506 protects allografts from rejection, but cancer progression is promoted in transplant recipients.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2007年第2期193-195,F0004,共4页
Chinese Journal of Experimental Surgery
基金
上海市科学技术委员会资助项目（044119608）
关键词
雷帕霉素
肝移植
肿瘤
Rapamycin
Liver transplantation
Neoplasm
