Ischemia impairs liver regeneration after major tissue loss in rodents: Protective effects of interleukin‐6
Ischemia impairs liver regeneration after major tissue loss in rodents: Protective effects of interleukin‐6
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DOI：
10.1002/hep.510300215
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发表时间：
1999-08
期刊：
影响因子：
13.5
通讯作者：
M. Selzner;Carlos A. Camargo;P. Clavien
中科院分区：
文献类型：
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作者：
M. Selzner;Carlos A. Camargo;P. Clavien
缺血对主要组织损失后肝脏再生能力的影响仍不清楚。白细胞介素-6 (IL-6) 已被证明可以在常温缺血和再灌注损伤模型中提供保护，并在主要肝切除术后启动肝细胞增殖。因此，我们研究了缺血对肝脏再生能力的影响，并评估了缺血和主要肝切除模型中IL-6在减少再灌注损伤和增强肝脏增殖中的作用。与仅接受肝切除术的动物相比，接受70%肝切除术和30分钟肝缺血的大鼠的再生能力（有丝分裂指数、增殖细胞核抗原和再生肝脏重量）显着降低。用重组白细胞介素-6 (rIL-6) 对接受肝切除术和缺血的动物进行预处理，将各个再生参数完全恢复到与仅接受肝切除术的动物相当的水平。在 IL-6 缺陷 (IL-6−/−) 小鼠中也获得了类似的结果。与接受相同实验条件的野生型小鼠相比，暴露于缺血和肝切除的 IL-6−/− 小鼠表现出肝再生受损。 rIL-6 的使用完全纠正了再生的每个参数，显示了 IL-6 在此类损伤中的特异性。在结合 45 分钟缺血和 68% 肝切除术的模型中研究了 IL-6 对动物存活的影响。用 rIL-6 预处理的 7 只动物中有 5 只 (71%) 永久存活，而所有对照动物在手术后 3 天内死亡（P = 0.02，Fisher 精确检验）。总之，研究表明缺血会严重损害肝脏的再生能力。 IL-6 似乎是减少损伤和促进缺血和主要组织损失后再生的关键保护分子。
The effects of ischemia on the regenerative capacity of the liver after major tissue loss remain unclear. Interleukin‐6 (IL‐6) has been shown to confer protection in models of normothermic ischemia and reperfusion injury and to initiate hepatocyte proliferation after major hepatectomy. Therefore, we investigated the effects of ischemia on the regenerative capacity of the liver and evaluated the role of IL‐6 in reducing reperfusion injury and enhancing hepatic proliferation in models combining ischemia and major hepatectomy. Rats subjected to 70% hepatectomy and 30 minutes of hepatic ischemia showed significantly reduced regenerative capacity (mitotic index, proliferating cell nuclear antigen, and regenerated liver weight) when compared with animals subjected to hepatectomy alone. Pretreatment of animals subjected to hepatectomy and ischemia with recombinant interleukin‐6 (rIL‐6) completely restored each parameter of regeneration to levels comparable with those of animals subjected to hepatectomy only. Similar results were obtained in IL‐6 deficient (IL‐6−/−) mice. IL‐6−/− mice exposed to ischemia and hepatectomy showed impaired hepatic regeneration when compared with wild‐type mice subjected to the same experimental conditions. The use of rIL‐6 completely corrected each parameter of regeneration showing the specificity of IL‐6 in this type of injury. The impact of IL‐6 on animal survival was studied in a model combining 45 minutes of ischemia and 68% hepatectomy. Five of 7 (71%) animals pretreated with rIL‐6 survived permanently, whereas all control animals died within 3 days of surgery (P = .02, Fisher's exact test). In conclusion, the study shows that ischemia dramatically impairs the regenerative capacity of the liver. IL‐6 appears to be a key protective molecule in reducing injury and promoting regeneration following combined ischemia and major tissue loss.