摘要
目的:探讨氨基胍对肺纤维化(PF)大鼠基质金属蛋白酶-13(MMP-13)和组织基质金属蛋白酶抑制物-1(TIMP-1)表达的影响及其对转化生长因子-β1/信号转导分子(TGF-β1/Smads)信号通路的调控机制。方法:SD大鼠随机分为4组:正常组、模型组、实验组、地塞米松组(对照组),每组30只。模型组、实验组、对照组大鼠气管滴注博莱霉素构建PF模型,正常组大鼠滴注等剂量等浓度氯化钠溶液。滴注完毕后,实验组、对照组大鼠每日分别腹腔注射1 ml氨基胍溶液(20 mg/kg)和1 ml地塞米松溶液(20 mg/kg),正常组、模型组分别腹腔注射等剂量生理盐水。处死大鼠,qRT-PCR、免疫组化、Western blot检测各组大鼠肺组织病理学及纤维化改变、TGF-β1、Smad2和Smad7 mRNA表达、MMP-13和TIMP-1表达、TGF-β1、p-Smad2、pSmad7蛋白表达。结果:与正常组相比,模型组肺组织TGF-β1和Smad2 mRNA表达、TGF-β1、p-Smad2和TIMP-1表达明显升高,Smad7 mRNA和p-Smad7蛋白表达、MMP-13表达明显降低;与模型组相比,实验组和对照组大鼠肺组织TGF-β1和Smad2mRNA表达、TGF-β1、p-Smad2、TIMP-1表达明显降低,Smad7 mRNA和p-Smad7蛋白表达、MMP-13表达明显升高(P<0.05)。结论:氨基胍可保护博来霉素诱导的PF大鼠肺组织,其抗纤维化作用可能通过调控TGF-β1/Smads信号通路实现。
Objective:To investigate effect of aminoguanidine on matrix metalloproteinase-13(MMP-13),tissue inhibitor of metalloproteinase-1(TIMP-1)in rats with pulmonary fibrosis(PF)and its regulation mechanism on transforming growth factor-β1/smads(TGF-β1/Smads)signaling pathway.Methods:SD rats were randomly divided into 4 groups:normal group,model group,experimental group,and dexamethasone group(control group),30 cases in each group.Rats in model group,experimental group and control group were given tracheal instillation of bleomycin to construct PF model,and rats in normal group were instilled with sodium chloride solution of equal dose and concentration.After infusion,rats in experimental group and control group were injected intraperitoneally with 1 ml of aminoguanidine solution(20 mg/kg)and 1 ml of dexamethasone solution(20 mg/kg)daily.Normal group and model group were injected intraperitoneally with equal dose of normal saline.Rats were sacrificed,qRT-PCR,immunohistochemistry,and Western blot to detect histopathology and fibrosis of lung tissues,mRNA expressions of TGF-β1,Smad2,Smad7,expressions of MMP-13 and TIMP-1,expressions of p-Smad2,p-Smad7 in each group.Results:Compared with normal group,mRNA expressions of TGF-β1 and Smad2,expressions of TGF-β1,p-Smad2,TIMP-1 in lung tissues of model group were significantly increased,mRNA expression of Smad7 and protein expressions of p-Smad7,expression of MMP-13 were significantly decreased.Compared with model group,mRNA expressions of TGF-β1 and Smad2,expressions of TGF-β1,p-Smad2,TIMP-1 in lung tissue of experimental and control groups were significantly decreased,mRNA expression of Smad7 and protein expression of p-Smad7,expression of MMP-13 were significantly increased(P<0.05).Conclusion:Aminoguanidine can protect lung tissue of bleomycin-induced PF rats,whose anti-fibrosis effect may be achieved by regulating TGF-β1/Smads signaling pathway.
作者
穆亚敏
黄希
宋志勇
MU Ya-Min;HUANG Xi;SONG Zhi-Yong(Xiangtan Medical and Health College,Xiangtan 410004,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第13期1558-1562,1570,共6页
Chinese Journal of Immunology
基金
2020年湖南省教育厅科学研究项目(20C1802)
2020年湖南省卫生健康委课题(20201598)。
