调节性T细胞促进放射性肺损伤大鼠体内β-连环蛋白介导的上皮细胞向间质转化和肺纤维化发展的机制  

Regulatory T cells promote β-catenin-mediated epithelial-to-mesenchymal transition and pulmonary fibrosis in rats with radiation-induced lung injury

作　　者：刘亚斌[1] 李庆 舒亚 朱静 LIU Ya-bin;LI Qing;SHU Ya(Department of Radiology,the First Affiliated Hospital of Chengdu Medical College,Chengdu Sichuan 610500,China)

机构地区：[1]成都医学院第一附属医院放射科,四川成都610500

出　　处：《临床和实验医学杂志》2022年第8期789-792,共4页Journal of Clinical and Experimental Medicine

基　　金：四川省医学科研课题计划项目(编号:Q18005)。

摘　　要：目的 研究调节性T细胞(Treg)促进放射性肺损伤大鼠体内β-连环蛋白介导的上皮细胞向间质转化和肺纤维化发展的机制。方法 将54只6~8周龄的雌性F344/N大鼠根据实验目的分为3组:对照组(正常大鼠,等剂量0.9%氯化钠溶液腹膜内注射),放射诱导组(肺损伤模型大鼠,等剂量0.9%氯化钠溶液腹膜内注射)和CD25抗体+放射诱导组(肺损伤模型大鼠,单克隆抗CD25抗体腹膜内注射,共注射4次),每组各18只。通过蛋白质印迹分析检测实验大鼠肺组织中β-连环蛋白的表达情况;流式细胞术检测调节性T细胞含量;苏木精-伊红染色对大鼠肺组织进行组织学检查,根据Szapiel评分对各组大鼠的肺泡炎和纤维化程度进行分析评分;酶联免疫吸附试验检测大鼠血液中羟脯氨酸和Ⅳ型胶原的含量。结果 处理后即刻至处理后2周,与对照组相比,放射诱导组大鼠的β-连环蛋白表达增加,而CD25抗体+放射诱导组较放射诱导组β-连环蛋白表达减少,差异均有统计学意义(P <0.05)。处理后即刻至处理后2周,放射诱导组较对照组肺泡炎和肺组织纤维化评分高,损伤严重,CD25抗体+放射诱导组评分较放射诱导组减少,差异均有统计学意义(P <0.05)。处理后即刻至处理后2周,与对照组相比,放射诱导组羟脯氨酸含量和Ⅳ型胶原含量增加,CD25抗体+放射诱导组羟脯氨酸含量和Ⅳ型胶原较放射诱导组含量下降,差异均有统计学意义(P <0.05)。处理后即刻至处理后2周,放射诱导组较对照组Tregs含量上升,而CD25抗体+放射诱导组Tregs含量较放射诱导组下降,差异均有统计学意义(P <0.05)。结论 调节性T细胞通过β-连环蛋白介导放射性肺损伤中EMT,促进肺部细胞纤维化和肺部胶原蛋白沉积,而通过阻断Treg可显著改善此现象。Objective To investigate the mechanism by which regulatory T cells promote β-catenin-mediated epithelial-to-mesenchymal transition and pulmonary fibrosis in rats with radiation-induced lung injury.Methods Fifty-four female F344/N rats aged 6-8 weeks were randomly divided into 3 groups:control group( normal rats,intraperitoneal injection of equal dose of normal saline),radiation induction group( lung injury model rats,intraperitoneal injection of equal dose of normal saline) and CD25 antibody + radiation induction group( lung injury model rats,intraperitoneal injection of monoclonal anti-CD25 antibody,4 injections in total) according to the purpose of the experiment,18 rats each.The expression of β-catenin in rat lung tissues was detected by Western blotting analysis.The content of regulatory T cells was detected by flow cytometry.The lung tissues of rats were histologically examined with hematoxylin-Eil stain,and the degree of alveolitis and fibrosis in each group was analyzed and scored according to Szapiel score.The contents of hydroxyproline and type Ⅳ collagen in the blood of rats were determined by enzyme-linked immunosorbent assay.Results Immediately after treatment to two weeks after treatment,compared with the control group,the expression of β-catenin was increased in the radiation-induced group,but decreased in the CD25 antibody + radiation-induced group compared with the radiation-induced group,and the differences were statistically significant( P < 0.05).Immediately after treatment to two weeks after treatment,compared with the control group,the scores of alveolitis and pulmonary fibrosis in the radiation-induced group were higher and more serious,and the scores of CD25 antibody + radiation-induced group were lower than those in the radiation-induced group,and the differences were statistically significant( P < 0.05).Immediately after treatment to two weeks after treatment,compared with the control group,the contents of hydroxyproline and type Ⅳ collagen in the radiation induced group were incre

关 键 词：大鼠 放射性肺损伤 调节T细胞 Β-连环蛋白 上皮间质转化 炎症反应 

分 类 号：R818[医药卫生—放射医学]