中国临床药理学杂志2024，Vol.40Issue(2)：244-248,5.DOI:10.13699/j.cnki.1001-6821.2024.02.019
SHP2调控巨噬细胞表型对系统性硬皮病纤维化病变的影响
Effects of SHP2 regulating macrophage phenotypic transformation on fibrotic lesions in systemic scleroderma
摘要
Abstract
Objective To investigate the effect of Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)on inflammatory response and fibrosis in mice with systemic scleroderma(SSc)and its mechanism.Methods Forty mice were randomly divided into blank group,model group and experimental-L,-H groups,with 10 mice in each group.Except the blank group,the othier three groups of mice were established SSc model.The experimental-L,-H groups were given PHPS1 treatment of 2.5 mg·kg-1 and 5 mg·kg-1,respectively;blank group and model group were intraperitoneally injected with 0.9％NaCl.Four groups of mice were given the drug once a day for 20 days.Immunofluorescence staining was used to detect the macrophage infiltration.Flow cytometry was used to determine the macrophage polarization,real-time quantitative fluorescence polymerase chain reaction was used to detect the expression of M1 macrophage markers tumor necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS)and M2 macrophage markers recombinant human arginase 1(Arg-1),transforming growth factor-β(TGF-β)in skin tissues and lung tissues.Results The proportions of M1-type macrophages labeled F4/80+CD86+in peripheral blood of experimental-H group,model group,blank group were(16.81±1.59)％,(36.95±3.54)％,(1.70±0.15)％,respectively;the proportions of M2-type macrophages labeled F4/80+CD206+were(18.49±1.76)％,(2.99±0.27)％,(16.62±1.49)％,respectively.The relative fluorescence intensity of F4/80 of macrophage marker in skin tissue were 1.46±0.13,2.14±0.19,1.00±0.04,respectively;TNF-α mRNA were 2.09±0.20,3.54±0.34,1.00±0.05,respectively;iNOS mRNA were 1.63±0.15,3.28±0.31,1.00±0.04,respectively,Arg-1 mRNA were 0.75±0.07,0.38±0.03,1.00±0.06,respectively,TGF-β mRNA were 0.79±0.08,0.41±0.04,1.00±0.04,respectively.In lung tissue,TNF-α mRNA were 1.46±0.14,2.61±0.25,1.00±0.04,respectively;iNOS mRNA were 1.53±0.15,2.82±0.29,1.00±0.03,respectively,Arg-1 mRNA were 0.67±0.07,0.31±0.03,1.00±0.05,respectively;TGF-β mRNA were 0.71±0.07,0.39±0.04,1.00±0.05,respectively.Compared with the model group,the above indexes in the experimental-H group had statistical significance(all P＜0.05).Conclusion The effect of SHP2 inhibitor on SSc mice can improve the inflammatory injury and fibrosis of skin and lung tissue,which is related to the regulation of macrophage polarization.关键词
系统性硬皮病/含Src同源2结构域蛋白酪氨酸磷酸酶/炎症/组织纤维化/巨噬细胞极化/肺损伤Key words
systemic scleroderma/Src homology 2 domain-containing protein tyrosine phosphatase/inflammation/tissue fibrosis/macrophages are polarized/lung injury分类
医药卫生引用本文复制引用
龙阳华,王珍真..SHP2调控巨噬细胞表型对系统性硬皮病纤维化病变的影响[J].中国临床药理学杂志,2024,40(2):244-248,5.基金项目
湖北省知识创新专项(自然科学基金)基金资助项目(2019CFB448) （自然科学基金）
