白介素6基因敲除小鼠肝脏移植后的肝脏再生研究

Liver graft regeneration after liver transplantation in IL-6 knockout mice

目的观察白介素6基因敲除（interleukin 6 knockout，IL-6 KO）小鼠原位肝移植后存活时间和肝脏再生的情况。方法建立正常小鼠（C57BL/6 wild type，C57BL/6 WT）和IL-6 KO小鼠的肝移植模型。38只小鼠分为3组：C57BL/6WT→C57BL/6 WT肝脏移植对照组（n=10），IL-6 KO→IL-6 KO肝脏移植组（n=14）和IL-6 KO→C57BL/6 WT肝脏移植组（n=14）。移植后观察小鼠肝移植物的存活情况。溴脱氧尿核苷（bromodeoxyuridine，BrdU）免疫组化检测移植肝脏的再生。结果实验各组肝移植物的冷缺血时间均〈1h。对照组小鼠肝移植后存活时间〉16d。IL-6 KO→IL-6 KO组的肝移植后移植物不能存活（2d）。IL-6 KO→C57BL/6 WT组的肝移植后移植物不能存活（1．6d）。实验各组间存活时间比较，差异有统计学意义（F=190．09，P〈0．01）。对照组小鼠肝脏移植后组织学检查证实肝脏组织损伤较轻，无组织坏死等改变。肝脏移植术后48h BrdU摄取轻度增加。IL-6 KO小鼠肝移植后，组织学检查表现出片状坏死和肝细胞气球样变等改变。肝移植术后48h免疫组化发现有极少数BrdU摄取。结论IL-6 KO小鼠的肝移植后肝再生反应障碍，肝移植物不能存活。IL-6是肝脏再生反应中一个重要因子。

Objective To observe recipient survival time and liver graft regeneration in an orthotopic liver transplantation model using IL-6 knockout mice as a donor. Methods A model of liver transplantation in C57BL/6 WT and IL-6 KO mice with C57BL/6 background was established. Thirty eight mice were divided into three groups： C57BL/6 wild type →C57BL/6 wild type control group（ n = 10）, IL-6 KO→IL-6 KO group（ n = 14） and IL-6 KO→C57BL/6 WT group（ n = 14）. Hepatocyte replication with BrdU uptake after liver transplantation was examined by immunohistochemistry. Results The survival time in the control group was 〉 16 days, and that was 2 days and 1.6 days in the IL-6 KO→IL-6 KO and IL-6 KO→C57BL/6 WT, respectively. The difference in survival time in all three groups was statistically significant （ F = 190. 09, P 〈 0. 01 ）. The liver grafts in control group showed minimal injury and no necrosis and mild increase of BrdU uptake at 48 hours. Patchy areas of necrosis and hepatocyte ballooning were observed in the two groups using IL-6 KO mice as donors, there was minimum increase in BrdU uptake at 48 hours post transplantation. Conclusion IL-6 KO liver grafts fail to regenerate after liver transplantation. IL-6 is an important factor in liver regerative response.