上调肝脏HO-1抑制肥大细胞脱颗粒减轻大鼠肝脏缺血再灌注损伤

目的 探索HO-1对肝脏缺血再灌注损伤中肥大细胞脱颗粒的影响。方法 将20只SD大鼠随机分成4组：假手术组（Sham组），缺血再灌注损伤组（I/RI组），HO-1诱导剂钴原卟啉组(CoPP组，术前24h给予CoPP，5 mg/kg)及HO-1抑制剂锌原卟啉组(ZnPP组，术前24h给予ZnPP，20 mg/kg)。建立大鼠缺血再灌注损伤模型，各组于再灌注后2h收集标本。RT-PCR检测肝脏组织HO-1 mRNA表达，Western blot检测肝脏组织HO-1蛋白表达；测定血清中ALT、AST水平；肝脏组织甲苯胺蓝染色检测肥大细胞脱颗粒数量，HE染色评价肝脏组织损伤情况。结果 与Sham组相比，I/RI组、CoPP组、ZnPP组大鼠组织HO-1 RNA和蛋白表达增加，血清ALT、AST水平升高，肥大细胞脱颗粒数量增多，肝脏细胞损伤加重。CoPP组与I/RI组相比，HO-1 mRNA和蛋白表达增加，血清ALT、AST水平减低，肥大细胞脱颗粒数量减少，肝细胞损伤减轻。ZnPP组与I/RI组相比，HO-1 mRNA和蛋白表达减少，血清ALT、AST水平升高，肥大细胞脱颗粒数量增多、肝细胞损伤严重。组间比较差异具有统计学意义(P＜0.05)。结论 HO-1过表达能减轻肝脏I/RI，其机制可能与抑制肝脏组织中肥大细胞脱颗粒有关。

HO-1 up-regulation decreases liver ischemia/reperfusion injury by inhibiting mast cells degranulation

Objective To investigate the effects of HO-1 on mast cells degranulation during liver ischemia/reperfusion injury. Methods SD rats ( n =20) were randomly divided into 4 groups : ( 1 ) sham operation group, (2) ischemia/reperfusion injury group (I/RI group), (3) CoPP group, CoPP was given before 24 h(5 mg/kg), (4) ZnPP group, ZnPP was given before 24 h (20 mg/kg). The rat model of liver ischemia/reperfusion was built. Samples were collected after 2 hours reperfusion. HO-1 mRNA expression was assessed by RT-PCR. The expression of HO-1 protein was assessed by Western blot. Serum ALT, AST levels were determined. The amount of degranulated mast cells were detected by toluidine blue staining. Liver injuries were evaluated by HE staining.Results Compared to sham group, liver HO-1mRNA and protein expression, ALT, AST levels, the number of degranulated mast cells significantly increased in I/RI group, CoPP group and ZnPP group. Moreover, liver injuries were more serious. Compared to I/RI group, there were increased HO-1mRNA and protein expression, reduced ALT, AST levels and the number of degranulated mast cells, also reduced liver injuries were found in CoPP group. Compared to I/RI group, the expression of HO-ImRNA and protein was down-regulated, ALT, AST levels elevated and the number of degranulated mast cells increased accompanying more serious liver injuries in ZnPP group.Conclusions HO-1 overexpression reduces liver ischemia/reperfusion injury, possibly by inhibiting mast cells degranulation in liver tissues.