大鼠部分肝移植后早期肝内细胞因子的变化  

Pattern of Early Intragraft Cytokines Following Rat Partial Liver Transplantation

作　　者：王国栋[1] 马毅[1] 陈规划[2] 

机构地区：[1]中山大学附属第一医院移植外科,广东广州510080 [2]中山大学附属第三医院移植外科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2008年第1期63-66,71,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家重点基础研究发展计划项目(973,2003CB515500)

摘　　要：【目的】研究不同冷缺血损伤条件下,肿瘤坏死因子-α和白介素-6等细胞因子在大鼠部分肝移植后的变化规律与肝脏再生的关系。【方法】建立Lewis大鼠50%部分原位肝移植模型。实验组分为:冷缺血1h、8h和16h组,每组20只。观察各组的生存率,并在术后90min、1、2、4和7d收集标本。检测不同冷缺血时间肿瘤坏死因子-α、白介素-6等细胞因子的表达。检测溴脱氧尿核苷摄取观察肝细胞DNA合成情况。【结果】共行60例大鼠部分肝脏移植,肝移植手术的成功率是100%。冷缺血1h、8h组的部分肝移植物存活率均为100%(>7d)。冷缺血16h后部分肝移植组存活率为20%(>7d)。与冷缺血1h相比,8h和16h的冷缺血损伤诱导大鼠部分肝移植物白介素-6(P<0.05)和肿瘤坏死因子-α(P<0.05)等因子表达增加。与冷缺血1h相比,冷缺血8h组的移植肝在移植术后24h摄取溴脱氧尿核苷明显增多(P<0.05)。冷缺血16h组的移植肝在移植术后24h仅有少数溴脱氧尿核苷染色阳性的肝细胞存在。【结论】肿瘤坏死因子-α和白介素-6等细胞因子的上调表达在启动和完成部分肝移植后早期肝脏再生的过程中非常重要。轻度(1h)和中度(8h)的冷缺血损伤可以启动并完成部分肝移植物移植后的肝脏再生,但重度(16h)的冷缺血损伤即使在早期启动信号存在的情况下,不能完成移植后的肝脏再生。[Objective] To explore the effect of different cold ischemia （CI） times on the patterns of intragraft cytokines of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） and their correlation with regeneration after rat partial liver transplantation. [Method] Model of Lewis rat 50% partial liver transplantation （LT） was established. The rats were divided into 3 groups： group of 1 h CI （20 cases）, group of 8 h CI （20 cases） and group of 16 h CI （20 cases）. Survival rate of each group was recorded. Specimens were collected at predetermined intervals from 90 min, 1, 2, 4, and 7 d post-reperfusion. Expression pattern of TNF-α and IL-6 were determined in liver grafts with different CI times following transplantation. Progression of DNA synthesis of hepatocyte was confirmed by bromodeoxyuridine （BrdU） uptake. [Results] A total of 60 Partial LTs were performed and operative success rate of partial LT was 100% in all groups. Survival in groups with 1 h and 8 h CI was 100% （ 〉 7 d）. Survival in group with 16 h CI was 20% （ 〉 7 d）. Compared with 1 h CI, IL-6 and TNF-α expression in partial liver grafts preserved for 8 h and 16 h were markedly increased post-transplantation （P 〈 0.05）. Positively BrdU-stained neclei were quantitated and analyzed between experimental groups. Number of positively stained neclei in 8 h CI group were more than those in 1 h CI groups at 24 h after transplantation （P 〈 0.05）, indicating the initiated and completed cell cycle progression and liver regeneration. At 24 h after transplantation, BrdU uptake was minimal in the rat livers with 16 h cold ischemia. [Conclusion] Upregulation of cytokines of TNF-α and IL-6 is an important factor in initiating and completing early partial liver graft regeneration. Mild （1 h） and moderate （8 h） CI could initiate and complete liver regeneration after rat partial LT, but partial grafts with severe CI （16 h） fail to achieve liver regeneration despite the presence of early initiating sig

关 键 词：冷缺血损伤 肝移植 白介素-6 肿瘤坏死因子 肝 再生 

分 类 号：R363[医药卫生—病理学]