期刊文献+

CTLA4-Ig抗大鼠肝移植排斥反应及诱导免疫耐受的实验研究 被引量:1

Application of Cytotoxic T Lymphocyte Antigen 4 Immunoglobulin G in Prevention of Rejection and the Induction of Immune Tolerance of Orthotopic Liver Transplantation in Rats
下载PDF
导出
摘要 目的建立大鼠原位肝移植(ROLT)急性排斥反应模型,探讨细胞毒淋巴细胞抗原4免疫球蛋白(CTLA4-Ig)抗排斥反应和诱导免疫耐受的作用.方法采用'二袖套管'法建立Wistar→SD大鼠配对组合的肝移植后排斥反应模型,并于术后第2天腹腔内一次性注射CTLA4-Ig(75 μg/只大鼠),与未给药的相同组合的排斥反应模型鼠对照研究,观察移植术后7 d 2组动物的一般情况、肝功能变化、移植肝病理改变及血清TNF-α水平的变化,同时观察CTLA4-Ig组动物术后4个月时的上述情况,以了解CTLA4-Ig抗排斥及诱导免疫耐受的作用.结果①对照组动物于肝移植术后6~14 d内相继死亡; 移植肝出现明显的排斥反应的病理改变征象. ②CTLA4-Ig组动物于术后7 d及4个月均未见明显的排斥反应表现,移植肝无明显的排斥反应的病理改变征象,血清TNF-α、ALT、AST、TBIL及DBIL水平均明显低于对照组(P<0.05),TP及Alb水平则明显高于对照组(P<0.05).结论 CTLA4-Ig有抗排斥反应及诱导免疫耐受功能的作用; 血清TNF-α水平作为观察ROLT后排斥反应的指标,可能有一定的参考价值. Objective This study was conducted to build tion in rat (ROLT) with the character of acute rejection; and to experimental model of orthotopic liver transplantastudy the effect of cytotoxic T lymphocyte antigen 4 immunoglobulin G (CTLA4-Ig) on prevention of rejection and the induction of immune tolerance of ROLT. Methods Build model of Wistar→SD ROLT(performed by the two cuff method) with character of acute rejection. Recipients were injected with CTLA4-Ig 75 big per ROLT into abdominal cavity after 2 days of operation. Contrast was made with no treatment group, the clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of TNF-α in serum were observed and measured on postoperative day 7. In treatment group, all above observation were done on postoperative month 4. Above all, determination of the effect of CTLA4-Ig on preventing acute rejection and inducing tolerance in ROLT was observed. Results ORecipients (no treatment group) died one by one within 6th-14th days; pathologic character of rejection in transplantation liver could be found; O In treatment group, on postoperative day 7 and month 4, no clinical rejection character and no pathologic character of rejection in transplantation liver were found and serum concentration of cytokins related to TNF-α found lower than that of contrast group (P〈 0.05 ), and serum concentration of ALT, AST, TBIL, DBIL found lower too(P〈0.05) ; But serum concentration of TP and Alb was found higher than that of contrast group (P〈0.05). Conclusion ① CTLA4-Ig treatment alone inhibits the rejection responce in ROLT. ② CTLA4-Ig treatment can Prevent rejection and induce immune tolerance in ROLT model with characters of acute rejection; the serum concentration of cytokins related to TNF-α can probably be used as evaluation standard of rejection in ROLT rejection.
出处 《中国普外基础与临床杂志》 CAS 2005年第6期600-604,共5页 Chinese Journal of Bases and Clinics In General Surgery
关键词 细胞毒淋巴细胞抗原4免疫球蛋白 肝移植 大鼠 排斥反应 免疫耐受 Cytotoxic T lymphocyte antigen 4 immunoglobulin G Liver transplantation Rat Rejection Immune tolerance
  • 相关文献

参考文献17

  • 1Renna-Molajoni E, Cinti P, Orlandini AM, et al. Contribution of the direct and indirect allorecognition pathway to the rejection of liver allografts [J]. Transplant Proc, 1998; 30(5): 2138
  • 2Renna-Molajoni E, Cinti P, Evangelista B, et al. Role of the indirect recognition pathway in the development of chronic liver allograft rejection [J]. Transplant Proc, 1998; 30(5): 2140
  • 3Vierling JM. Immunology of acute and chronic hepatic allograft rejection [J]. Liver Transpl Surg, 1999; 5(4 Suppl 1): S1
  • 4Bretscher P. The two-signal model of lymphocyte activation twenty-one years later [J]. Immunol Today, 1992; 13(2): 74
  • 5Lafferty KJ. A few steps along the path to adult transplantation tolerance [J]. Transplant Proc, 1999; 31(1-2A): 11S
  • 6No authors listed. Banff schema for grading liver allograft rejection: an international consensus document [J]. Hepatology, 1997; 25(3): 658
  • 7Neumann UP, Fischer U, Schmitz V, et al. Long-term graft acceptance after rat liver allograft transplantation induced by application of CTLA4-Ig and donor specific spleen cell administration [J]. Transplant Proc, 2002; 34(5): 1400
  • 8Li W, Lu L, Wang Z, et al. CTLA4-Ig inhibits rejection of mouse liver allografts from Flt3-ligand-treated donors and is associated with increased lymphocyte apoptosis [J]. Transplant Proc, 2001; 33(1-2): 246
  • 9Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [J]. Science, 1992; 257(5071): 789
  • 10Larsen CP, Elwood ET, Alexander DZ, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways [J]. Nature, 1996; 381(6581): 434

同被引文献17

  • 1申立中,金伯泉,夏海滨,朱勇,刘雪松.TLSF_(JM)对DNFB诱导的小鼠接触性皮炎和同种异体皮片移植排斥反应的抑制作用[J].细胞与分子免疫学杂志,1996,12(4):27-31. 被引量:9
  • 2Tzakis AG, Nery JR, Thompson J, et al. New immunosup pressive regimens in clinical intestinal transplantation [J]. Transplant Proc, 1997; 29(1-2) : 683
  • 3Fung JJ, Starzl TE. FK506 in solid organ transplantation [J]. Transplant Proc, 1994; 26(5) : 3017
  • 4Guo WH, Tian L, Dallmann MJ, et al. Comparative study of allograft survival of heterotopic and orthotopic small bowel transplantation in rat [J]. Transplantation, 2003; 75(11) : 1895
  • 5Higuchi K, Kimura O, Furukawa T, et al. FK506 induces the atrophy of enteric ganglia in small bowel transplantation, which can be prevented by the neuropeptide bombesin [J]. Transplant Proc, 2006; 38(6):1823
  • 6Grant D. Current results of intestinal transplantation. The In ternational Intestinal Transplant Registry [J]. Lancet, 1996; 347(9018) : 1801
  • 7Jiang H, Kobayashi M. Differences between cyclosporin A and tacrolimus in organ transplantation [J]. Transplant Proc, 1999; 31(5) : 1978
  • 8Miyauchi T, Ishikawa M, Tashiro S, et al. Effect of donor- specific splenocytes via portal vein and FK506 in rat small bowel transplantation[J]. Transplantation, 1998; 65(1) : 27
  • 9Guo WH, Tian L, Chan KL, etal. Role of CD4^+ and CD8^+ T cells in early and late acute rejection of small bowel allograft [J]. J Pediatr Surg, 2001, 36(2) : 352
  • 10Ma H, Wang J, Wang J, et al. Features of chronic allograft rejection on rat small intestine transplantation [J]. Pediatr Transplant, 2007, 11(2) : 165

引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部