摘要
目的探讨IL-22/IL-22BP轴在肝脏缺血/再灌注损伤中的作用及可能的机制。方法建立小鼠短、中、长时间肝脏缺血/再灌注损伤模型,通过检测血清IL-22、肝脏IL-22BP mRNA、IL-22Rα1 mRNA及STAT3通路相关蛋白表达水平,明确IL-22及IL-22BP在肝脏缺血/再灌注损伤中的作用及机制。结果相比短时间缺血/再灌注组,中、长时间缺血/再灌注组表现出更为严重的再灌注损伤。随着缺血时间延长,血清IL-22浓度升高,但肝内STAT3通路的激活却被明显抑制,IL-22BP/IL-22Rα1 mRNA比值呈现出明显增加趋势。给予外源性重组IL-22,遭受长时间缺血/再灌注损伤的小鼠肝损伤明显减轻,肝内STAT3通路被明显激活。结论在肝脏缺血/再灌注损伤过程中,IL-22表现出保肝作用,而IL-22BP/IL-22Rα1 mRNA比值是肝损伤负向指标,其机制可能与IL-22/IL-22BP轴对STAT3通路激活的调控有关。
Aim To investigate the role of IL-22/IL-22BP axis in hepatic ischemia-reperfusion injury and its potential mechanism.Methods Short,medium,and long-term liver ischemia-reperfusion injury(IRI)and IRI+IL-22 mouse models were established,then the serum IL-22 concentration,IL-22BP mRNA,IL-22Rα1 mRNA and STAT3 pathway related protein expression in liver were detected to study the role and mechanism of IL-22 and IL-22BP in liver IRI.Results Compared with short-term ischemia-reperfusion injury group,mice in middle and long-term ischemia-reperfusion injury groups showed more severe liver injury.The concentration of serum IL-22 significantly increased but the activation of STAT3 pathway was significantly inhibited in long-term ischemia-reperfusion group.The ratio of IL-22BP/IL-22Rα1 mRNA increased significantly with the prolongation of ischemia time.Liver injury was significantly alleviated and the activation of STAT3 pathway was markedly up-regulated after the administration of exogenous recombinant IL-22 in mice with long-term ischemia-reperfusion injury.Conclusions IL-22 can protect liver from ischemia-reperfusion injury;however,IL-22BP/IL-22Rα1 mRNA ratio is a negative indicator of liver injury,and the mechanism may be related to the regulation of STAT3 pathway activation by IL-22/il-22bp axis during liver IRI.
作者
周恒
黄三雄
贺颖
何晓玮
郭璐
鲁晟
ZHOU Heng;HUANG San-xiong;HE Ying;HE Xiao-wei;GUO Lu;LU Sheng(Dept of Pharmacy,The First People’s Hospital of Huzhou,First Affiliated Hospital of Huzhou University,Huzhou Zhejiang 313000,China;Dept of Hepatobiliary Surgery,The First People’s Hospital of Huzhou,First Affiliated Hospital of Huzhou University,Huzhou Zhejiang 313000,China;Central Laboratory, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou Zhejiang 313000, China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2021年第7期1015-1020,共6页
Chinese Pharmacological Bulletin
基金
浙江省自然科学基金资助项目(No LQ20H310002)
湖州市科技局资助项目(No 2018GYB28)。
作者简介
周恒(1988-),男,硕士,研究方向:肝脏药理学,E-mail:912358033@qq.com;通讯作者:鲁晟(1974-),男,学士,主任药师,研究方向:肝脏药学,E-mail:870500189@qq.com。
