LOXL2、TGF-β、CTGF在结缔组织病合并间质性肺病患者使用环磷酰胺治疗前后的变化及临床意义

The changes and clinical significance of LOXL2,TGF-β and CTGF in patients with connective tissue disease associated with interstitial lung disease before and after treatment with cyclophosphamide

目的:观察血清赖氨酰氧化酶样蛋白2(lysyl oxidase-like protein 2,LOXL2)、转化生长因子β(transforming growth factor-β,TGF-β)、结缔组织生长因子(connective tissue growth factor,CTGF)在结缔组织病合并间质性肺病(connective tissue disease and interstitial lung disease,CTD-ILD)患者使用环磷酰胺治疗前后的变化及临床意义。方法:选择2021年3月-2022年5月在内蒙古科技大学包头医学院第一附属医院风湿免疫科收治的CTD-ILD并使用环磷酰胺针静脉滴注治疗的患者30例,观察患者治疗前基线期及使用环磷酰胺治疗12周后及24周后的临床资料、影像学资料及实验室资料,分析血清LOXL2、TGF-β、CTGF在CTD-ILD患者使用环磷酰胺治疗前后的变化及临床意义。结果:CTD-ILD患者使用环磷酰胺治疗24周后血清ESR、IgM、IgA、IgG水平明显降低,肺功能指标TLC、FVC、FEV1/FVC、DLCO%明显改善(P<0.05);治疗12周后及24周后血清LOXL2、TGF-β、CTGF的水平明显降低,6-MWT明显改善。HRCT评分与CRP评分明显降低(P<0.05);治疗12周后及24周后C-反应蛋白及血气分析指标PaO_(2)与PaCO_(2)变化差异不大(P>0.05)。CTD-ILD患者血清中LOXL2水平与ESR、IgA、IgG呈正相关(P<0.05);LOXL2与TGF-β、CTGF呈正相关(P=0.001、0.003);TGF-β与CTGF呈正相关(P=0.025)。结论:环磷酰胺治疗可能通过抑制血清LOXL2的表达进一步抑制TGF-β信号通路进而影响CTGF的表达而有效地控制CTD-ILD患者的肺纤维化。

Objective:To observe the changes and clinical significance of serum lysyl oxidase-like protein 2(LOXL2),transforming growth factor-β(TGF-β)and connective tissue growth factor(CTGF)in patients with connective tissue disease and interstitial lung disease(CTD-ILD)before and after treatment with cyclophosphamide.Methods:From March 2021 to May 2022,30 patients with CTD-ILD who were admitted to the Department of Rheumatology and Immunology,the First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology and treated with intravenous infusion of cyclophosphamide were selected.The clinical data,imaging data and laboratory data of patients at baseline before treatment and 12 weeks and 24 weeks after treatment with cyclophosphamide were observed.The changes and clinical significance of serum LOXL2,TGF-β and CTGF in patients with CTD-ILD before and after treatment with cyclophosphamide were analyzed.Results:After 24 weeks of treatment with cyclophosphamide,the levels of serum ESR,IgM,IgA and IgG in patients with CTD-ILD were significantly decreased,and the lung function indexes TLC,FVC,FEV1/FVC and DLCO%were significantly improved(P<0.05).After 12 weeks and 24 weeks of treatment,the levels of serum LOXL2,TGF-β and CTGF were significantly decreased,and 6-MWT was significantly improved.HRCT score and CRP score were significantly lower(P<0.05).There was no significant difference in C-reactive protein and blood gas analysis indexes PaO_(2) and PaCO_(2) after 12 weeks and 24 weeks of treatment(P>0.05).The level of serum LOXL2 in CTD-ILD patients was positively correlated with ESR,IgA and IgG(P<0.05).LOXL2 was positively correlated with TGF-β and CTGF(P=0.001,0.003),TGF-β was positively correlated with CTGF(P=0.025).Conclusion:Cyclophosphamide may inhibit TGF-β signaling pathway by inhibiting the expression of serum LOXL2,and then affect the expression of CTGF to effectively control pulmonary fibrosis in patients with CTD-ILD.