白介素22融合蛋白对刀豆蛋白A诱导肝损伤病理状态下肝切除后肝再生的影响

Effects of IL-22-Fc fusion protein on liver regeneration in mice after hepatectomy under ConA-induced hepatic injury condition

目的研究白介素22融合蛋白(IL-22-FP)对刀豆蛋白A(Con A)诱导急性肝损伤后行70%肝切除手术(PHx)的小鼠术后肝再生及肝脏保护的作用。方法建立小鼠Con A肝损伤和PHx手术模型,术后32 h通过过量麻醉法处死小鼠。5-溴脱氧尿嘧啶核苷染色,观察小鼠肝脏再生情况;全自动生化分析仪检测小鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平;HE染色观察小鼠肝脏组织损伤情况;Western blot法检测小鼠肝组织中增值细胞核抗原(PCNA)、细胞周期蛋白D1(Cycli D1)、信号转导子及转录激活子3(STAT3)及p-STAT3蛋白的表达情况。结果 Con A+PHx+IL-22-FP组小鼠同Con A+PHx+rh-IL-22组及其他组小鼠相比,表现出更多的肝细胞增殖和更高的肝指数(肝脏重量/体重);HE染色显示Con A+PHx+IL-22-FP组小鼠肝脏坏死及炎症细胞浸润程度较低;生化检测显示ConA+PHx+IL-22-FP组血清ALT和AST水平明显低于其他组;Western blot结果表明Con A+PHx+IL-22-FP组小鼠的肝脏组织PCNA、Cyclin D1和p-STAT3蛋白的表达量也明显高于其他组。结论 IL-22-FP能够促进由Con A诱导肝损伤的小鼠PHx后的肝再生,并表现出显著的肝脏保护作用。

Objective To study the effects of IL-22-Fc fusion protein（IL-22-FP） on liver regeneration and hepato- protection in mice after partial hepatectomy（PHx） under Concanavalin A （ConA） induced hepatic injury condition. Methods ConA-induced liver injury and partial hepatectomy model was built firstly, liver injury and regeneration was checked at 32 hours after hepatectomy. Hepatic cells proliferation were detected by 5-bromodeoxyuridine stai-ning of liver tissue. The degree of liver injury and hepatic necrosis were demonstrated by HE staining. Serum ala-nine aminotransferase（ ALT） and aspartate aminotransferase（ AST） levels in mice were measured with automatic bi-ochemical analyzer. The expression levels of PCNA, CyclinDl and p- STAT3 protein were tested by Western blot technique. Results Compared with the recombinant human IL-22 treatment group and other groups, both the pro-liferation of hepatic cells and the liver weight/body weight （ LW/BW） ratios of the IL-22-FP treatment group （the experimental group） were significantly increased. The degree of liver necrosis and inflammatory cells infiltration shown in HE staining in the experimental group were apparently reduced. The serum ALT and AST levels were sig-nificantly decreased in the experimental group than in the other groups. The expression of PCNA,CyclinDl and p- STAT3 protein in the experimental group were obviously up-regulated than that in the other groups. Conclusion Treatment with IL-22-FP contributes to the liver protection and regeneration in mice with hepatectomy after ConA- induced liver injury.