摘要
目的:研究不同冷缺血损伤条件下,大鼠肝脏移植后肝脏再生的分子机制。方法:建立大鼠原位肝移植模型。实验分为:冷缺血1h、8h和16h组。观察各组的生存率,并在术后90min、1、2、4和7d收集标本,观察白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、信号转导激活蛋白3(STAT3)等表达情况。免疫组化检测细胞周期素D1的表达和肝细胞摄取溴脱氧尿核苷情况。比较实验各组肝脏移植后TNF-α和IL-6的表达水平。分析实验各组移植术后48h溴脱氧尿核苷染色阳性的肝细胞数。结果:冷缺血1h、8h和16h后肝脏移植物的存活率均为100%(>14d)。移植术后90min,与冷缺血1h组相比,冷缺血8h和16h组大鼠移植肝内TNF-α等因子表达明显增加(P<0.05)。移植术后90min,与冷缺血1h和8h组相比,16h组IL-6的表达亦明显增强(P<0.05)。冷缺血8h和16h组STAT3活性明显增强。冷缺血8h组细胞周期素D1在胞浆和细胞核内均有表达。冷缺血16h组细胞周期素D1仅在核内表达。肝细胞复制活跃。与冷缺血1h和8h组相比,冷缺血16h组术后48h溴脱氧尿核苷染色阳性的肝细胞计数也明显增多(P<0.05)。结论:大鼠肝脏移植物经受16h冷缺血损伤后仍然能够启动,完成肝脏再生,修复组织损伤。大鼠肝脏移植后的肝脏再生可能通过TNF-α/IL-6/STAT3/cyclinD1/DNA合成的途径调节。
AIM ： To study the molecular mechanisms of liver regeneration following different cold ischemia （Cl） times after liver transplantation in a rat model. METHODS： A model of rat orthotopic liver transplantation was established. The rats were divided into 3 groups： 1 h Cl group, 8 h Cl group and 16 h Cl group. Survival rate in each group was recorded. Specimen were collected at predetermined intervals from 90 min, 1, 4 and 7 d post - reperfusion. The patterns of TNF -α, IL-6 and STAT3 activation were determined in liver grafts with 1 h, 8 h and 16 h CI times. Expression of cyclin D1 and hepatocyte replication with bromodeoxyuridine （BrdU） were confirmed by immunohistochemistry. The resuits of TNF -α and IL -6 expression in all groups were analyzed after whole liver transplantation. Statistical analysis was used to compare BrdU positively stained hepatocytes at 48 h post - reperfusion. RESULTS： Liver transplantation was successfully performed in all experimental groups. Survival rate in each group was 100% （ 〉 14 d）. Compared with 1 h Cl, TNF-α expressions in whole liver grafts with 8 h and 16 h Cl were markedly increased at 90 min after reperfusion （P 〈 0.05）. Compared with 1 and 8 h Cl, IL -6 expression in liver grafts preserved for 16 h were markedly increased at 90 min after transplantation （P 〈0.05 ）. With 8 and 16 h Cl, STAT3 activity was markedly increased. Cyclin D1 expression in 8 Cl group was demonstrated with cytoplasmic and nuclear staining at 24 h in liver grafts. Cyclin D1 expression was mainly nuclear in 16 h Cl group. Extensive hepatocyte replication was present. The numbers of hepatoeytes with positively stained nuclei in 16 h Cl group were more than those in 1 and 8 h Cl group at 48 h after transplantation（P〈0. 05）. CONCLUSION： Rat whole liver grafts with 16 h Cl injury still initiate and complete liver regeneration and graft recovery after liver transplantation. Liver regeneration following transplantation may be through TNF - α/IL -6/STAT3/cyclin D1/DNA
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第8期1561-1564,共4页
Chinese Journal of Pathophysiology
基金
国家重点基础研究发展计划(973计划)基金资助项目(No.2003CB515500)
关键词
冷缺血损伤
肝移植
肝再生
Cold ischemic injury
Liver transplantation
Liver regeneration
