作者：甄瑾，春梅，李敏，刘斌，王梅玲，云永利，柳雅洁，马翔凌

单位：

010017内蒙古自治区呼和浩特市，内蒙古自治区人民医院神经内科 通信作者：甄瑾，E-mail：zhenjin2006106@126.com

Units：

Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Huhhot 010017, China Corresponding auther: ZHEN Jin, E-mail: zhenjin2006106@126.com

关键词：

多发性硬化; 白介素22; 星形胶质细胞; 细胞转化; 补体C3;

Keywords：

Multiple sclerosis; Interleukin 22; Astrocyte; Cell transformation; Complement C3

CLC：

DOI：

10.12114/j.issn.1008-5971.2022.00.308

Funds：

内蒙古自治区自然科学基金项目（2019MS08077）；内蒙古自治区卫生健康科技计划项目（202201029）

摘要：

目的 探究白介素(IL)-22对星形胶质细胞转化的促进作用及可能机制。方法 本实验时间为2020-06-20至2021-09-23。根据研究目的将人星形胶质细胞进行分组，并给予相应处理。采用qPCR检测补体C3、FKBP5、GGTA1、Serping1、Srgn mRNA表达水平，采用Western blot法检测补体C3蛋白、磷酸化p38(p-p38)、磷酸化-丝裂原活化蛋白激酶活化的蛋白激酶2(p-MAPKAPK-2)表达水平。比较对照组、IL-22处理组、C1q+肿瘤坏死因子α(TNF-α)+IL-1α处理组、C1q+TNF-α+IL-1α+IL-22处理组补体C3 mRNA、蛋白表达水平，对照组和IL-22处理组FKBP5、GGTA1、Serping1、Srgn mRNA表达水平，对照组、IL-22处理组、丝裂原活化蛋白激酶p38(p38 MAPK)抑制剂处理组、IL-22+p38 MAPK抑制剂处理组p-p38、p-MAPKAPK-2、补体C3蛋白表达水平。结果 IL-22处理组、C1q+TNF-α+IL-1α处理组及C1q+TNF-α+IL-1α+IL-22处理组补体C3 mRNA、蛋白表达水平高于对照组，C1q+TNF-α+IL-1α处理组和C1q+TNF-α+IL-1α+IL-22处理组补体C3 mRNA、蛋白表达水平高于IL-22处理组(P<0.05)。IL-22处理组FKBP5、GGTA1、Serping1、Srgn mRNA表达水平高于对照组(P<0.05)。IL-22处理组p-p38、p-MAPKAPK-2、补体C3蛋白表达水平高于对照组，p38 MAPK抑制剂处理组p-p38、p-MAPKAPK-2、补体C3蛋白表达水平低于对照组(P<0.05)；IL-22+p38 MAPK抑制剂处理组p-p38、p-MAPKAPK-2、补体C3蛋白表达水平低于IL-22处理组，但高于p38 MAPK抑制剂处理组(P<0.05)。结论 IL-22可促进星形胶质细胞向A1型星形胶质细胞转化，其机制可能与IL-22促进丝裂原活化蛋白激酶活化的蛋白激酶2(MAPKAPK-2)磷酸化，进而激活p38-丝裂原活化蛋白激酶(MAPK)信号通路有关。

Abstract：

【Abstract】　Objective To investigate the promoting effect of interleukin (IL) -22 on astrocytes transformation and its possible mechanism. Methods The experiment was conducted from June 20, 2020 to September 23, 2021. According to the purpose of the study, human astrocytes were grouped and treated accordingly. The expression levels of complement C3, FKBP5, GGTA1, Serping1 and Srgn mRNA were detected by qPCR. The expression levels of complement C3 protein, phosphorylated p38 (p-p38) , phosphorylated mitogen activated protein kinase activated protein kinase 2 (p-MAPKAPK-2) were detected by Western blot. The expression levels of complement C3 mRNA and protein in the control group, IL-22 interventional group, C1q+tumor necrosis factor-α (TNF-α) +IL-1α interventional group and C1q+TNF-α+IL-1α+IL-22 interventional group were compared. The mRNA expression levels of FKBP5, GGTA1, Serping1 and Srgn between control group and IL-22 interventional group were compared. The expression levels of p-p38, p-MAPKAPK-2 and complement C3 protein in control group, IL- 22 interventional group, p38 MAPK inhibitor interventional group and IL-22+p38 MAPK inhibitor interventional group were compared. Results The expression levels of mRNA and protein of complement C3 in IL-22 interventional group, C1q+TNF- α+IL-1α interventional group and C1q+TNF-α+IL-1α+IL-22 interventional group were higher than those in control group, and the expression levels of mRNA and protein of complement C3 in C1q+TNF-α+IL-1α interventional group and C1q+TNF- α+IL-1α+IL-22 interventional group were higher than those in IL-22 interventional group (P < 0.05) . The mRNA expression levels of FKBP5, GGTA1, Serping1 and Srgn in IL-22 interventional group were higher than those in the control group (P < 0.05) . The expression levels of p-p38, p-MAPKAPK-2 and complement C3 protein in IL-22 interventional group were higher than those in control group, and the expression levels of p-p38, p-MAPKAPK-2 and complement C3 protein in p38 MAPK inhibitor treatment group were lower than those in control group (P < 0.05) . The expression levels of p-p38, p-MAPKAPK-2 and complement C3 protein in IL-22+p38 MAPK inhibitor treatment group were lower than those in IL-22 interventional group, while higher than those in p38 MAPK inhibitor treatment group (P < 0.05) . Conclusion IL-22 can promote the transformation of astrocytes to A1 type astrocytes, and its mechanism may be related to IL-22 promoting mitogen activated protein kinase activated protein kinase 2 (MAPKAPK-2) phosphorylation and activating p38-mitogen activated protein kinase (MAPK) signaling pathway.

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