白细胞介素-22对刀豆蛋白A介导肝损伤小鼠部分肝切除后肝再生的作用  

The role of interleukin - 22 in liver regeneration after partial hepatectomy with concanavalin A - mediated liver injury in mice

作　　者：刘子荣[1] 张雅敏[2] 杨超[1] 杨龙[2] 崔子林[2] 沈中阳[2] 

机构地区：[1]天津医科大学一中心临床学院,300192 [2]天津市第一中心医院肝胆外科,300192

出　　处：《中华实验外科杂志》2016年第2期365-369,共5页Chinese Journal of Experimental Surgery

基　　金：天津市应用基础与前沿技术研究计划资助项目（14JCYBJC24800）;国家自然科学基金（81370576）

摘　　要：目的探讨刀豆蛋白A介导的肝损伤小鼠行部分肝切除术后白细胞介素-22（IL-22）对其肝脏再生的治疗作用及其机制。方法100只C57／BL6小鼠，随机分成部分肝切除（PH）组（单-70％肝切除组）、刀豆蛋白A（ConA）组（单一刀豆蛋白A损伤组）、ConA＋PH组（刀豆蛋白A损伤后行70％肝切除组）和ConA＋IL-22＋PH组（刀豆蛋白A损伤后经IL-22干预再行70％肝切除组），然后每组分别于术后32、40、48h、1、2周各处死5只，取其肝脏组织。称肝叶质量计算肝再生率，行病理切片观察各时间点的病理损伤，免疫组织化学法检测不同时间点肝脏组织中增殖细胞核抗原（PCNA）的含量，计算PCNA指数，Western blot检测细胞周期蛋白Dl（Cyclin D1）、信号传导与转录激活因子3（STAT3）水平了解细胞周期改变。结果经IL-22处理后，小鼠肝再生显著，术后各时间点（40、48h、1、2周），ConA＋PH＋IL-22干预组小鼠肝质量／体质量（3．16±0．17、3．34±0．13、4．19±0．14、5．14±0．16）明显高于ConA＋PH组（2．95±0．14、3．09±0．14、3．78±0．10、4．89±0．12），显著减轻ConA对肝组织的损伤，且在术后各时间点ConA＋PH损伤组再生肝组织内STAT3蛋白和Cyclin D1蛋白表达量明显低于其余组，经IL-22预处理后再生肝组织内STAT3蛋白和Cyclin D1蛋白表达量明显高于其余组。结论IL-22在ConA介导的肝损伤小鼠部分肝切除术后再生过程中有明显的促进作用，该作用可能是IL-22通过与受体结合后激活STAT3介导的信号通路，从而活化Cyclin D1表达，促进肝细胞增殖再生，修复肝损伤。Objective To study the therapeutic effects and mechanisms of interleukin - 22 （IL- 22 ） in liver regeneration after partial hepatectomy with concanavalin A （ConA） -mediated liver iniury in mice. Methods C57/BL6 were divided into four groups with 25 mice per group： Partial hepatecto- my （PH） group, ConA group, PH ＋ ConA group, and PH ＋ ConA ＋ IL - 22 group. The liver tissue at 32, 40, 48 h, 1 w and 2 w after resection were obtained. Before sampling liver were weighted and calculated liver regeneration rate. Pathological changes were observed by hematoxylin - eosin staining. The expression and index of proliferating cell nuclear antigen （PCNA） in liver tissue were tested by immunohistoehemical method. The levels of Cyclin D1 and signal transducer and activator of transcription 3 （STAT3） signaling pathway detected by Western blotting analysis. Results With administration of exogenous IL - 22, the liver weigh/body increased significantly, compared with ConA ＋ PH group （ 2. 95 ± 0. 14, 3.09±0. 14, 3.78±0. 10, 4. 89 ± 0. 12）, ConA ＋ PH ＋ IL - 22 group （3. 16 ± 0. 17, 3.34± 0. 13, 4. 19 ± 0. 14, 5.14 ±0. 16） increased and reached statistical significance at 40, 48 h, 1 w or 2 w. Histopathology indicated that liver injury in mice of the treatment group was markedly alleviated. Furthermore, Western blotting revealed that in the four groups, STAT3 and Cyelin D1 level are the most significantly increased in the ConA ＋ PH ＋ IL - 22 group as well as the least significantly increased in the ConA ＋ PH group at all the time points. Conclusion IL - 22 acts as a protective eytokine to attenuate liver injury in the model of hepatectomy in T cell - mediated hepatitis induced by eoneanavalin A. This effect of IL - 22 might be mediated by enhancing pro - growth pathways via STAT3 activation and then inducing the expression of genes important for cell cycle progression （such as Cyclin D1 ）.

关 键 词：白细胞介素-22 刀豆蛋白A 部分肝切除术 肝再生 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]