诱导血红素氧合酶-1对脂肪供肝缺血再灌注损伤的影响

目的 探讨诱导血红素氧合酶-1(HO-1)是否可减轻大鼠脂肪变性供肝移植后缺血再灌注损伤及其机制.方法 sD大鼠敢予高脂饲料喂养4周后彤成轻度脂肪变性供肝;随机分为3组,A组(n=25)供肝切取前24 h腹腔注射血晶素125 mg/kg;B组(n=25)供肝切取前24 h腹腔注射血晶素125 mg/kg,移植肝血流开放时静脉注射Znpp 1.5 mg/kg,C组(n=25)供肝切取前腹腔注射生理盐水;受体肝移植后3、6、12、24、48 h分别取移植肝组织检测HO-1活性,放射免疫法检测血清中肿瘤坏死因子中(TNF)-α水平,苏木素-伊红(HE)染色病理学检查缺血再灌注损伤程度.结果 术后各时段HO-1活性A组均显著强于B组及C组(P<0.05),而B组和C组比较差异无统计学意义(P>0.05);术后各时段肿瘤坏死因子-α水平A组均显著低于B组及C组(P<0.05),而B组和C组比较差异无统计学意义(P>0.05);各组移植肝缺血再灌注损伤以术后12 h最为明显,A组表现为轻度,而B组及C组表现为中度缺血再灌注损伤.结论 诱导HO-1可通过抑制TNF-α的表达而减轻脂肪供肝移植术后缺血再灌注损伤.

Influence of induced heme oxygenase-1 on ischemia-reperfusion injury of fatty liver transplantation

Objective To investigate whether induced heme oxygenase-1(HO-1)could alleviate the ischemia-reperfusion injury in fatty liver transplantation and the mechanism. Methods Before liver tansplantation, mild steatotic liver was established by high fat diet for 4 weeks, and then the rats were di-vided into 3 groups randomly. In group A(n = 25 ), heroin was injected intraperitoneally 24 h before resec-tion of donor liver. In group B(n = 25 ), heroin was injected intraperitoneally 24 h before resection of donor liver,and rats were infused with ZnPP at the end of surgery after unclamping the vessel. In group C(n = 25),saline was injected intraperitoneally 24 h before resection of donor liver. The liver and serum samples in the recipients were collected 3,6,12,24 and 48 h after transplantation. The activity of HO-1 and TNF-α level were detected. And the histological changes were observed under a light microscope. Results The post-operative activity of HO-1 in group A was significantly higher than that in groups B and C, but there was no significant difference between groups B and C. The TNF-α level in group A was significantly lower than that in groups B and C,but there was no significant difference between groups B and C. All rat livers showed the most serious ischemia-reperfusion injury at 12 h after reperfusion, and the damage was milder in group A than that in the other two groups. Conclusion HO-1 can alleviate the ischemia-reperfnsion in-jury of fatty liver transplantation by inhibiting the TNF-α expression.