IL-22介导的STAT3信号通路对急性重症胰腺炎小鼠的保护作用

doi:10.6040/j.issn.1671-7554.0.2015.001

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (6): 1-6.doi: 10.6040/j.issn.1671-7554.0.2015.001

• 基础医学 • 下一篇

IL-22介导的STAT3信号通路对急性重症胰腺炎小鼠的保护作用

白金霞¹, 白金运², 石秀菊¹, 许洪伟¹

1. 山东大学附属省立医院消化科, 山东济南 250021;
2. 山东大学医学院, 山东济南 250012

收稿日期:2015-01-04 修回日期:2015-03-31 出版日期:2015-06-10 发布日期:2015-06-10
通讯作者: 许洪伟。 E-mail:xu_hong_wei@sina.com E-mail:xu_hong_wei@sina.com
基金资助:
山东省科技发展计划(2013YD18052)

IL-22 protects mice from acute severe pancreatitis via STAT3 signaling pathway

BAI Jinxia¹, BAI Jinyun², SHI Xiuju¹, XU Hongwei¹

1. Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
2. School of Medicine, Shandong University, Jinan 250012, Shandong, China

Received:2015-01-04 Revised:2015-03-31 Online:2015-06-10 Published:2015-06-10

摘要/Abstract

摘要： 目的探讨外源性重组小鼠白细胞介素22(rIL-22)对左旋精氨酸诱导的小鼠急性重症胰腺炎(SAP)的保护作用及其介导的信号通路。方法 60只雄性Balb/c小鼠随机分为正常对照组(NaCl组,10只)、SAP组(30只)、治疗对照组(PBS组,10只)和治疗组(rIL-22组,10只)。以8%左旋精氨酸(4 g/kg体质量,腹腔注射2次)诱导小鼠SAP模型,NaCl组注射等量0.9%NaCl。PBS组和rIL-22组分别应用PBS或rIL-22(200 ng/次×5次)在相应时间点进行腹腔注射。光镜下观察胰腺组织病理学改变,检测血清淀粉酶活性。Real-time PCR法检测胰腺组织中IL-22RA1、胰腺再生源蛋白3β(Reg3β)和Reg3γ、B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-xL基因在mRNA水平的表达。Western blotting方法检测胰腺组织总STAT3和磷酸化STAT3蛋白的表达。对PBS组和rIL-22组的死亡率进行统计。结果 SAP组72 h胰腺组织出现典型的SAP病理改变;随时间延长,SAP组Reg3β和Reg3γ、Bcl-2和Bcl-xL mRNA的表达水平呈递减趋势,血清淀粉酶活性和IL-22RA1 mRNA表达水平先上升后下降。与PBS组相比,rIL-22组血清淀粉酶明显降低(P<0.05),胰腺病理损伤减轻,死亡率下降(P<0.05),胰腺组织磷酸化STAT3表达增加(P<0.05),Reg3β、Reg3γ、Bcl-2、Bcl-xL和IL-22RA1 mRNA的表达上调(P<0.05)。结论外源性重组IL-22通过激活STAT3信号通路,活化下游抗菌肽和抗凋亡基因的表达,对左旋精氨酸诱导的SAP小鼠起保护作用。

关键词: 信号转导与转录激活因子3, 白细胞介素-22, 抗菌肽, 急性重症胰腺炎

Abstract: Objective To investigate the effect of interleukin-22 (IL-22) in acute severe pancreatitis (SAP) induced by L-arginine and its signal pathway. Methods Sixty male Balb/c mice were randomly divided into 4 groups, the normal control group(NaCl group, n=10), SAP group(n=30), treatment control group (PBS group, n=10) and treatment group(rIL-22 group, n=10). Mice were induced intraperitoneally with L-arginine(two doses, 4 g/kg each, 1 hour apart). PBS or rIL-22 (200 ng/time, 5 times) was administrated to mice at the indicated times in PBS and rIL-22 groups. Serum amylase and pancreas tissue histopathology were examined. IL-22RA1, regenerating islet-dedrived protein 3β(Reg3β), Reg3γ, B cell lymphoma/lewmia-2(Bcl-2), Bcl-xL mRNA were detected by Real-time PCR. STAT3 expression and activation were assessed by Western blotting. Mortality ratios in PBS and IL-22 group were counted. Results Seventy-two hours after L-arginine administration, typically histopathological changes were observed in SAP group. The expressions of Reg3β, Reg3γ, Bcl-2 and Bcl-xL mRNA decreased progressively, while serum amylaseand IL-22RA1 mRNA increased until 48 hours, but decreased apparently at 72 hours. Compared with those in PBS group, rIL-22 group showed lower serum amylase(P<0.05), slighter pathological changes and lower mortality(P<0.05). Compared with those in PBS group, the expressions of Reg3β, Reg3γ, Bcl-2, Bcl-xL, IL-22RA1 mRNA and phospho-STAT3 protein in rIL-22 group markedly increased(P<0.05). Conclusion Exogenous recombinant IL-22 protects mice from L-arginine induced SAP by enhancing the expressions of antimicrobial peptides and antiapoptotic genes through the STAT3 signaling pathway.

Key words: Signal transducer and activator transcription 3, Interleukin-22, Acute severe pancreatitis, Antimicrobial peptide

中图分类号:

R576

白金霞, 白金运, 石秀菊, 许洪伟. IL-22介导的STAT3信号通路对急性重症胰腺炎小鼠的保护作用[J]. 山东大学学报（医学版）, 2015, 53(6): 1-6.

BAI Jinxia, BAI Jinyun, SHI Xiuju, XU Hongwei. IL-22 protects mice from acute severe pancreatitis via STAT3 signaling pathway[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(6): 1-6.

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IL-22介导的STAT3信号通路对急性重症胰腺炎小鼠的保护作用

IL-22 protects mice from acute severe pancreatitis via STAT3 signaling pathway

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