炎症性细胞因子致肝脏缺血再灌注损伤和丹参单体的保护作用

作者	单位
王洪超	中日友好医院临床医学研究所
张华	中日友好医院临床医学研究所
周童亮	中日友好医院临床医学研究所
乔军	中日友好医院临床医学研究所
胡晓明	中日友好医院临床医学研究所
赵武述	中日友好医院临床医学研究所

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中文摘要:

目的 :探讨肿瘤坏死因子α(TNFα)和白细胞介素 8(IL 8)在肝脏缺血再灌注损伤中的变化以及水溶性丹参单体MP 1(简称MP 1)的作用。方法 :建立人肝窦内皮细胞体外低温缺氧再氧化模型和大鼠离体肝脏缺血再灌注损伤模型 ,以台盼蓝染色观察细胞损伤情况 ,用放免法分析透明质酸吸收率来反映肝窦内皮细胞的功能 ,用ELISA方法检测肝窦内皮细胞产生的TNFα和IL 8水平 ,以胆汁流出速率和ALT、AST、LDH的变化反映肝脏功能。结果 :低温缺氧再氧化期间 ,肝窦内皮细胞的死亡率随着时间的增加而增加 ,TNFα和IL 8的释放也随之增加 ,但肝窦内皮细胞的功能下降 ;肝窦内皮细胞死亡率分别与TNFα和IL 8的释放呈正相关 (r =0 94 9,P <0 0 5和r =0 892 ,P <0 0 5 )。加入TNFα抗体低温缺氧再氧化 6h的内皮细胞死亡率降低 ;重组TNFα处理的肝窦内皮细胞死亡率明显增加 ;离体大鼠肝脏的功能随低温保存和再灌注时间的增加而降低 ;MP 1能明显降低人肝窦内皮细胞的死亡率及TNFα和IL 8的释放 ,同时可以减轻离体大鼠肝脏的缺血再灌注损伤。结论 :TNFα直接参与肝窦内皮细胞的缺血再灌注损伤 ,MP 1可能通过抑制TNFα和IL 8的途径来减轻肝脏缺血再灌注损伤。

英文摘要:

Objective: To observe the changes of tumor necrosis factor α (TNFα), interleukin 8 (IL 8) in liver ischemia/reperfusion injury and the protective effect of hydrophilic Salvia monomer MP 1 on them. Methods: Hypothermic hypoxia reoxygenation model of human liver sinusoidal endothelial cell line and ischemia/reperfusion model of isolated rat liver were used. TNFα and IL 8 were measured with ELISA kits. Cell injury was excluded by trypan blue stain, sinusoidal endothelial cell function was assessed by hyaluronic acid uptake rate through RIA. Liver function was assayed by alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) release as well as output of bile flow. Results: During hypoxia reoxygenation, sinusoidal endothelial cell injury, TNFα and IL 8 increased significantly in time dependent manner, while sinusoidal cell function decreased. Cell injury was positively correlated to the released amount of TNFα (r=0 949,P<0 05)and IL 8 (r=0 892,P<0 05), respectively, the mortality could be reduced within 6 hrs by adding anti TNFα monoclonal antibody and increased by treating with recombinant human TNFα. Function of isolated rat liver lowered alone the increasing of low temperature ischemia/reperfusion time. MP 1 could markedly lower the mortality of endothelial cells and TNFα and IL 8 release, it also could alleviate ischemia/reperfusion injury to isolated rat liver. Conclusion: TNFα participated in liver ischemia/reperfusion injury directly, and MP 1 might alleviate the injury through inhibiting TNFα and IL 8.

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