血红素氧合酶-1对肝脏缺血再灌注损伤的保护作用

目的:探讨血红素氧合酶-1(HO-1)对肝脏缺血再灌注损伤的保护作用机制。方法:SD大鼠30只,建立二套袖法原位肝移植模型。随机分为3组:对照组,无任何处理;CoPP处理组,供肝收获前24h供体腹腔注射HO-1诱导剂CoPP5mg/kg。;ZnPP处理组,腹腔注射抑制剂ZnPP20mg/kg。移植后第三天检测肝脏移植物肝功能,免疫组织化学方法检测肝脏移植物HO-1的表达情况。TUNEL法检测凋亡变化。以Suzuki标准评分来反映肝脏移植物的缺血再灌注损伤程度。结果:①CoPP组ALT,AST较对照组和ZnPP组明显降低(P<0.01)。②HO-1表达:CoPP组明显高于其他组(P<0.05)。③移植物凋亡阳性细胞百分率:CoPP组明显低于对照组和ZnPP组(P<0.05)。④肝脏移植物病理变化:CoPP组和与对照组,ZnPP组比较,炎症细胞浸润少,肝细胞损伤轻。肝脏移植物Suzuki评分,CoPP组(0.76±0.59)明显低于对照组(1.32±0.74)与ZnPP组(1.80±0.70),有显著统计学差异(P<0.05)。结论:HO-1对肝脏移植物缺血再灌注损伤具有保护作用,其机制可能与抗炎症与抗凋亡有关。

Protective Effects of HO-1 in Liver Ischemia Reperfusion Injury

Objective To study the protective effects and mechanisms of HO-1 system in ischemia reperfusion injury. Methods Orthotopic liver transplantation with modified Kamada's two cuff technique was established in 30 SD rats.They were randomly divided into 3 groups:control group without any treatment, donors pretreated with HO-1 inducer CoPP (5mg/kg,intraperitoneally) 24 h before transplantation (Copp group),donors pretreated with HO-1 inhibiter ZnPP(20 mg/kg,intraperitoneally) 24 h before transplantation (Znpp group). Items were tested as following:①The level of serum ALT,AST in graft 3 d after transplantation. ②The level of HO-1 expression of the graft 3 d after transplantation with immunohistology. ③The apoptosis index of grafts 3 d after transplantation was examined by TUNEL method. ④The pathological changes in ischemia reperfusion injury of graft were evaluated by International Suzuki's Criteria. Results ①The level of serum ALT and AST in CoPP group was significantly lower than that in the other two groups (P<0.05).②The expression of H0-1 in CoPP group was higher than that in control group(P<0.01).③Compared to control group, the index of apoptosis of grafts was decreased in CoPP group(P<0.01).④Compared to the other two groups, CoPP group had fewer neutrophil infiltration and lower grade of liver cell injury. Suzuki's scores of CoPP group (0.76±0.59) were lower than that in control group(1.32±0.74)and in ZnPP group(1.80±0.70)(P<0.05). Conclusion Overexpression of HO-1 has a protective effect in liver ischemia reperfusion injury,this effect may be performed through its anti-inflammatory and anti-apoptotic functions