IL-35亚基EBI3、P35对系统性硬化症小鼠肺部和皮肤炎症及肺纤维化的影响  

Effect of IL-35 subunits EBI3 and P35 on lung and skin inflammation and pulmonary fibrosis in systemic sclerosis mice

作　　者：卢春秀[1] 王迪 潘婕 潘冬梅[1] 曾雯 廖晓玲 雷玲[1] Lu Chunxiu;Wang Di;Pan Jie;Pan Dongmei;Zeng Wen;Liao Xiaoling;Lei Ling(Department of Rheumatology and Immunology,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;The Affiliated Suzhou Kowloon Hospital of Shanghai Jiao Tong University School of Medicine,Suzhou 215000,China)

机构地区：[1]广西医科大学第一附属医院风湿免疫科,南宁530021 [2]上海交通大学医学院附属苏州九龙医院,苏州215000

出　　处：《广西医科大学学报》2023年第5期866-870,共5页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.82060300);广西自然科学基金资助项目(No.2020GXNSFAA297146)。

摘　　要：目的:研究白细胞介素(IL)-35亚基对系统性硬化症(SSc)小鼠肺部和皮肤炎症及肺纤维化的影响。方法:将24只雌性BALB/c小鼠随机分为4组:正常对照组、SSc模型组、SSc+EB病毒诱导的基因3抗体(SSc+EBI3 mAb)组和SSc+IL-12A P35抗体(SSc+P35 mAb)组,除正常对照组外,其余各组小鼠注射博来霉素构建SSc模型。造模后,SSc+EBI3 mAb组和SSc+P35mAb组分别腹腔注射100μL的EBI3 mAb、P35 mAb。采用苏木精—伊红(HE)染色观察小鼠皮肤和肺组织炎症病理改变,Masson染色观察肺纤维化程度,免疫组化法检测皮肤和肺组织α-平滑肌肌动蛋白(α-SMA)表达,酶联免疫吸附试验(ELISA)法检测血清IL-35、IL-6、IL-10水平。结果:与对照组相比,SSc模型组小鼠皮肤厚度增加,肺纤维化评分、皮肤和肺组织炎症评分、血清IL-35水平及皮肤和肺组织α-SMA表达水平均升高,血清IL-10水平降低(均P<0.05)。与SSc模型组比较,SSc+EBI3 mAb组和SSc+P35 mAb组小鼠皮肤厚度增加,血清IL-10水平及皮肤、肺组织α-SMA表达水平升高,血清IL-35水平降低(均P<0.05);SSc+P35 mAb组小鼠肺纤维化评分较SSc模型组升高(P<0.05)。与SSc+EBI3 mAb组相比,SSc+P35 mAb组小鼠血清IL-10水平升高(P<0.05)。结论:IL-35可能通过EBI3和P35亚基抑制SSc小鼠模型皮肤和肺部的纤维化病变,而对炎症无明显作用,P35亚基在肺纤维化中的作用更明显。Objective:To investigate the effect of interleukin(IL)-35 subunits on lung and skin inflammation and pulmonary fibrosis in systemic sclerosis(SSc)mice.Methods:24 female BALB/c mice were randomly divided into four groups:normal control group,SSc model group,SSc+Epstein-Barr virus-induced gene 3 antibody(EBI3 mAb)group and SSc+IL-12Ap35 antibody(SSc+P35 mAb)group.Except for the normal control group,mice in the other groups were injected with bleomycin to establish the SSc model.After modeling,the SSc+EBI3 mAb group and SSc+P35 mAb group were injected with 100μL of EBI3 mAb and P35 mAb by intraperitoneal injection,respectively.The skin and lung tissue inflammatory histological changes were observed by hematoxylin-eosin(HE)staining,the degree of pulmonary fibrosis was observed by Masson staining,α-smooth muscle actin(α-SMA)expression in skin and lung tissue was detected by immunohistochemistry and the serum levels of IL-35,IL-6,and IL-10 were detected by enzyme linked immunosorbent assay(ELISA).Results:Compared with the control group,mice in the SSc model group showed an increase in skin thickness,pulmonary fibrosis score,skin and lung tissue inflammation score,serum IL-35 level,andα-SMA expression in skin and lung tissue,as well as a decrease in serum IL-10 level(all P<0.05).Compared with the SSc model group,the skin thickness of mice in the SSc+EBI3 mAb group and SSc+P35 mAb group increased,serum IL-10 level andα-SMA expression in skin and lung tissue increased,and serum IL-35 level decreased(all P<0.05).Compared with the SSc group,the mice in the SSc+P35 mAb group had a higher pulmonary fibrosis score(P<0.05).Compared with the SSc+EBI3 mAb group,the serum IL-10 level in the SSc+P35 mAb group of mice increased(P<0.05).Conclusion:IL-35 may inhibit skin and pulmonary fibrosis in the SSc mouse model through EBI3 and P35 subunits,but has no significant effect on inflammation.The role of P35 subunits in pulmonary fibrosis is more obvious.

关 键 词：系统性硬化症 白细胞介素35 EB病毒诱导的基因3 P35 

分 类 号：R593.2[医药卫生—内科学]