缺血预处理对肝大部切除术中残肝缺血再灌注损伤的保护作用

Protection of ischemic preconditioning was lost in the rat model of major hepatectomy with ischemia/reperfusion injury

目的观察缺血预处理对大鼠肝大部切除术中残肝缺血再灌注损伤的保护作用。方法健康的雌性 SD 大鼠随机分为3组:即单纯肝叶切除组(PH 组)、缺血再灌注损伤状态下肝叶切除组(IR 组)及缺血预处理组(IP 组)。分别取术前及术后0.5、6、12、24、48 h 等时间点,应用全自动生化分析仪检测血清 ALT、AST 含量,通过免疫组织化学法检测残肝组织中 Ki67和 Cyclin D1表达变化,采用放免法检测血清中透明质酸(HA)含量。结果 IP 组术后24 h 内各检测点的 AST和 ALT 值明显高于 PH 组和 IR 组(P<0.05)。术后早期 IP 组大鼠的血清 HA 表达量明显高于 PH组和 IR 组(P<0.05)。PH 组大鼠肝细胞 Ki67和 Cyclin D1表达在术后24 h 达到峰值,并且明显高于 IR 组和 IP 组大鼠(P<0.05)。其中 IP 组大鼠术后 Ki67和 Cyclin D1表达量降低地最显著。结论在合并肝组织大部缺失时,缺血预处理对残留肝组织的缺血再灌注损伤的保护效应消失,它损害了大鼠残肝再生功能。

Objective To investigate whether ischemic preconditioning can protect residual liver of rats from ischemia/reperfusion injury after major hepatectomy. Methods Female Wistar rats were randomly divided into 3 groups ： group PH ,rats subjected to 70% hepatectomy alone ; group IR,rats subjected to 30 rain of total hepatic ischemia, and 70% hepatectomy was performed just before reperfusion; group IP, rats pretreated with IP （5/10 rain）. Before and O. 5,6,12,24 and 48 h after operation serum AST and ALT activities were measured using an autoanalyzer. The expression of Ki67 and Cyclin D1 was detected by using immunohistochemical methods in residual liver tissue, and the levels of serum HA were determined by radioimmunoassay. Results The levels of serum AST and ALT were significantly higher in group IP than in group PH and group IR from 0.5 -24 h after 70 % PH （ P 〈 0. 05）. In the early stage after 70% PH the levels of serum HA were significantly higher in group IP than in PH and IR groups. The expression of Ki67 and Cyclin D1 reached the peak at 24 h after PH in group PH,which was significantly higher than that in groups IR and IP （ P 〈 0.05 ）. And in group IP it was decreased significantly compared with that in groups PHand IR （ P 〈 0.05 ）. Conclusion Protection of ischemic preconditioning from ischemia/reperfusion injury of residual liver was lost after major hepatectomy in rats due to impair of the residual liver regeneration.