Grant D, Duff J, Zhong R, Garcia B, Lipohar C, Keown P, Stiller C
Department of Surgery, University of Western Ontario, London, Canada.
Transplantation. 1988 Feb;45(2):279-84. doi: 10.1097/00007890-198802000-00005.
To date, it has not been possible to reliably prevent intestinal allograft rejection in large animals. This study was undertaken to determine if continuous i.v. cyclosporine (CsA) followed by p.o. CsA would prevent rejection in outbred piglets with orthotopic, in-continuity intestinal allografts. Untreated recipients (n = 7) died of rejection (2), interstitial pnuemontitis (3), or technical complications (2) at 5.3 +/- 1 days. Intestinal recipients treated with i.v. CsA 8 mg/kg/day and i.v. steroids (n = 3) died of rejection (mean survival 11.3 +/- 3.2 days). CsA 20 mg/kg/day i.v. plus i.v. steroids for 21 days, followed by p.o. CsA 25 mg/kg/day (n = 6) prevented rejection; however, most of the recipients developed fatal infections (mean survival 28 +/- 8 days). Intravenous CsA 15 mg/kg/day for 7-10 days (n = 16), followed by p.o. CsA 30 mg/kg/day in tapering doses reliably prevented graft rejection, permitting long-term survival (mean survival 121 +/- 32 days). Rejection did not occur in 7 animals when CsA was discontinued at 97 +/- 11 days. Seven animals surviving more than 100 days maintained normal nutritional indices and gained weight at the same rate as control animals. This study provides a rationale for further experimentation to determine the feasibility of intestinal transplantation in man.
迄今为止，在大型动物中可靠地预防肠道同种异体移植排斥反应仍未实现。本研究旨在确定持续静脉注射环孢素（CsA）后口服CsA是否能预防杂种仔猪原位连续性肠道同种异体移植的排斥反应。未经治疗的受体（n = 7）在5.3±1天死于排斥反应（2例）、间质性肺炎（3例）或技术并发症（2例）。接受8 mg/kg/天静脉注射CsA和静脉注射类固醇治疗的肠道受体（n = 3）死于排斥反应（平均存活11.3±3.2天）。20 mg/kg/天静脉注射CsA加静脉注射类固醇21天，随后口服25 mg/kg/天CsA（n = 6）可预防排斥反应；然而，大多数受体发生了致命感染（平均存活28±8天）。15 mg/kg/天静脉注射CsA 7 - 10天（n = 16），随后逐渐减量口服30 mg/kg/天CsA可可靠地预防移植物排斥反应，实现长期存活（平均存活121±32天）。当在97±11天停用CsA时，7只动物未发生排斥反应。7只存活超过100天的动物维持了正常的营养指标，体重增加速度与对照动物相同。本研究为进一步试验以确定肠道移植在人类中的可行性提供了理论依据。
