摘要
目的探讨血红素氧合酶-1(HO-1)在大鼠同种异体移植肝脏的过表达对移植后早期血清肿瘤坏死因子-α(TNF-α)及肝脏结构功能的影响。方法90只Wistar大鼠随机分为生理盐水预处理组(S1组)、钴原卟啉预处理组(S2组)和锌原卟啉预处理组(S3组),每组30只。各组随机取出24只分为供受体,供体于预处理后24h行原位肝移植,余6只仅行预处理,分别于供体预处理后24h、门静脉复流后1h和3h各取6只取血及肝组织,分别检测血清ALT、AST、TNF-α水平、肝组织形态学变化及HO-1蛋白表达水平。结果①供肝预处理后24h,各组血清转氨酶及TNF-α水平无显著性差异(P>0.05),门静脉复流后各时间点,S2组血清转氨酶及TNF-α水平均低于S1组和S3组(P<0.05),S1组低于S3组(P<0.05);②供肝预处理后24h,S2组肝脏HO-1蛋白即有较高表达,S1组和S3组只有极少量表达;门静脉复流后各时间点,S2组均高于S1组和S3组(P<0.05),S1组高于S3组(P<0.05);③移植肝门静脉复流后3h,S2组肝脏损伤轻于S1组和S3组,S1组轻于S3组。结论HO-1在大鼠同种异体移植肝脏中的过表达可减少血清TNF-α释放,显著改善移植后的肝脏功能,减轻供肝的缺血再灌注损伤。
Objective To investigate the effects of overexpression of heme oxygenase - 1 ( HO - 1 ) in the graft liver of rat on serum TNF - α and liver structure and function after liver transplantation. Methods Ninety Wistar rats were randomized into 3 groups: Saline pretreatment group (group S1, n =30), Cobalt protoporphyrin IX chloride pretreatment group (group S2, n = 30) and zinc protoporphyrin IX pretreatment group ( group S3, n = 30). The at 24 rats were divided into donors and recipients in each experiment group and for orthotopic liver transplantation 24h after donor pretreatment, the other 6 rats were simply pretreated. At 24h after donor pretreatment and lh, 3h after portal vein reperfusion, blood samples were obtained to determine the levels of serum ALT and AST. The level of serum TNF - α was detected by radioimmunity. Simultaneously liver tissues were taken, the changes of liver tissues Were observed by HE staining. The expression of HO - 1 protein was detected by immunohistochemistry. Results ①There was no difference of the lever of serum ALT, AST, TNF - α for each experiment group after 24h pretreatment ( P 〉 0.05 ). At each time point after portal vein reperfusion, the levels of ALT, AST, TNF-α in group S2 was significantly lower than that in group S1 and S3 (P 〈 0. 05 ) , it in group S1 was significantly higher than that in group S3 (P 〈 0. 05 ) ; ②Expression of heme oxygenase - 1 protein was slight in group S3 and S1 after 24h pretreatment, and there was no difference between two groups. In group S2 it had increased after 24h pretreatment and was significantly higher than that in group S1 and Sz (P 〈 0. 05 ) . At each time point after portal vein reperfusion, it in group $2 was significantly higher than that in group S1 and S3 (P 〈 0. 05 ) , it in group S1 was significantly higher than that in group S3 ( P 〈 0.05 ) ; ③Degree of graft liver injury at 3h after portal vein reperfusion in group S2 was lighter than that in group S1 and S3 , and it in group S1 was lighter than that in group S2. Conclusion The overexpression of HO - 1 protein in graft liver can decrease the releasing of serum TNF - α, improve the transplantated liver function and alleviate its injury.
出处
《医药论坛杂志》
2008年第2期44-46,48,F0004,共5页
Journal of Medical Forum
关键词
HO-1
TNF-α
大鼠
肝移植
缺血再灌注损伤
Heme oxygenase - 1
TNF -α
Rat
Liver transplantation
Ischemia andreperfusion injury