Zhang Ai-bin, Zheng Shu-sen, Jia Chang-ku, Wang Yan
Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of College of Medicine, Zhejiang University and Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. cheung163 @163.com
Chin Med J (Engl). 2004 Mar;117(3):408-12.
We investigated the role of 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) in preventing allograft from acute rejection following orthotopic liver transplantation.
A rat orthotopic liver transplantation model was used in this study. SD-Wistar rats served as a high responder strain combination. Recipients were subjected to administration of 1,25-(OH)2D3 at dosages ranging from 0.25 microg.kg(-1).d(-1) to 2.5 microg.kg(-1).d(-1). Survival after transplantation as well as pathological rejection grades and IFN-gamma mRNA, IL-10 mRNA transcription intragraft on day 7, and day 30 post-transplantation were observed.
After recipients were treated with 1,25(OH)2D3 at dosages of 0.5 microg.kg(-1).d(-1) or 1.0 microg.kg(-1).d(-1), survivals of recipients were prolonged. Ninety-five percent confidence intervals of survival were 46 - 87 days and 69 - 102 days (both P = 0.0005 vs control group), respectively. On day seven post-transplantation, relative levels of IFN-gamma mRNA transcription were 0.59 +/- 0.12 and 0.49 +/- 0.16, which was higher than the control group (P = 0.005, P = 0.003, respectively). Relative levels of IL-10 mRNA transcription were 0.83 +/- 0.09 and 0.76 +/- 0.09, which was lower than the control group (P = 0.002, P = 0.003, respectively). At a dosage of 0.5 microg.kg(-1).d(-1), the median of pathological rejection grade on day seven and on day thirty post-transplantation were 1.5 and 2.0 in comparison with the CsA-treated group (P = 0.178, P = 0.171, respectively). At a dosage of 0.5 microg.kg(-1).d(-1), the median of pathological rejection grade on day seven and day thirty post-transplantation were 1.5 and 1.5 in comparison with CsA-treated group (P = 0.350, P = 0.693, respectively).
After each recipient was treated with 1,25-(OH)2D3 at a dosage of (0.5 - 1.0) microg.kg(-1).d(-1), transcription of cytokine intragraft was accommodated effectively and deviated to Th2 type, resulting in alleviation of acute rejection. 1,25-(OH)2D3 can prolong survival of recipient after orthotopic liver transplantation.
我们研究了1,25 - 二羟基维生素D3（1,25-(OH)2D3）在原位肝移植后预防同种异体移植物急性排斥反应中的作用。
本研究采用大鼠原位肝移植模型。SD - 威斯塔大鼠作为高反应性品系组合。受体接受剂量范围为0.25μg·kg⁻¹·d⁻¹至2.5μg·kg⁻¹·d⁻¹的1,25-(OH)2D3给药。观察移植后的存活情况以及移植后第7天和第30天的病理排斥分级和移植物内IFN - γ mRNA、IL - 10 mRNA转录情况。
受体接受0.5μg·kg⁻¹·d⁻¹或1.0μg·kg⁻¹·d⁻¹剂量的1,25(OH)2D3治疗后，受体存活时间延长。存活的95%置信区间分别为46 - 87天和69 - 102天（与对照组相比，P均 = 0.0005）。移植后第7天，IFN - γ mRNA转录的相对水平分别为0.59±0.12和0.49±0.16，高于对照组（分别为P = 0.005，P = 0.003）。IL - 10 mRNA转录的相对水平分别为0.83±0.09和0.76±0.09，低于对照组（分别为P = 0.002，P = 0.003）。在0.5μg·kg⁻¹·d⁻¹剂量下，移植后第7天和第30天的病理排斥分级中位数与环孢素A治疗组相比分别为1.5和2.0（分别为P = 0.178，P = 0.171）。在0.5μg·kg⁻¹·d⁻¹剂量下，移植后第7天和第30天的病理排斥分级中位数与环孢素A治疗组相比分别为1.5和1.5（分别为P = 0.350，P = 0.693）。
每个受体接受(0.5 - 1.0)μg·kg⁻¹·d⁻¹剂量的1,25-(OH)2D3治疗后，移植物内细胞因子转录得到有效调节并偏向Th2型，从而减轻急性排斥反应。1,25-(OH)2D3可延长原位肝移植后受体的存活时间。
