外源性H_2S对肺纤维化大鼠肺组织转化生长因子-β1及结缔组织生长因子的干预作用  

Effect of exogenous hydrogen sulfide on transforming growth factor-β1 and connective tissue growth factor in lung tissue of pulmonary fibrosis rats

作　　者：曹华[1] 马红英[2] 曹霞[3] 黄新莉 张雪静 周晓红 

机构地区：[1]河北中医学院基础医学院,河北石家庄050091 [2]航天中心医院超声科 [3]四川大学华西公共卫生学院

出　　处：《中国老年学杂志》2014年第1期140-142,共3页Chinese Journal of Gerontology

基　　金：河北省卫生厅医学重点指令项目(No.20100028)

摘　　要：目的动态观察硫化氢(H2S)对博莱霉素(BLM)致肺纤维化大鼠肺组织转化生长因子(TGF-β1)及结缔组织生长因子(CTGF)表达的影响。方法采用气管内一次注射BLM 5 mg/kg致大鼠肺纤维化的造模方法,将健康雄性Wistar大鼠54只随机分为对照组、肺纤维化组和NaHS(H2S供体)+肺纤维化组,造模后第2天开始:NaHS+肺纤维化组每天腹腔注射0.5 ml NaHS(28μmol/kg),对照组及肺纤维化组每天腹腔内注射等量生理盐水。各组在给药后7、14、28 d分别随机处死6只取材,碱水解法检测肺组织羟脯氨酸(HYP)水平的变化,免疫组化法检测TGF-β1及CTGF蛋白在肺组织的表达。结果与对照组相比,肺纤维化组各期大鼠肺组织HYP含量、TGF-β1及CTGF蛋白表达均显著升高(P【0.01);与肺纤维化相比,NaHS+肺纤维化各组大鼠HYP含量、TGF-β1及CTGF蛋白表达在各期均显著降低(P【0.01、0.05)。各组各期肺组织TGF-β1与CTGF呈显著正相关(r=0.891~0.968,P均【0.01)。结论外源性H2S可以通过抑制TGF-β1信号通路,下调CTGF蛋白表达发挥抗纤维化作用。Objective To investigate the effect of exogenous hydrogen sulfide on transforming growth factor-(TGF-β1) and connec- tive tissue growth factor(CTGF) in lung tissue of pulmonary fibrosis Rats.Methods Fifty-four pathogen-free Male Wistar rats were ran- domly divided into three groups: control,pulmonary fibrosis model and NaHS(the H 2 S donor) and pulmonary fibrosis groups with 18 rats in each group.Rats in each group were then divided into three subgroups based on time of study(7-,14- and 28-days).Pulmonary fibrosis model was established by intrabronchus instillation of bleomycin(5 mg / kg).While control rats received saline,rats of the treated group sim- ultaneously were administered intraperitoneal injections of NaHS(28 μmol / kg) daily.Hydroxyproline level in lung homogenate was meas- ured by the alkaline hydrolysis assay.The expressions of TGF-β1 and CTGF in lung tissue were analyzed by ELISA.Results The content of HYP,TGF-β1 and CTGF in rat's lung tissue of pulmonary fibrosis group in each time point were significantly higher than that of control group(P<0.01).The contents of HYP,TGF-β1 and CTGF in rat's lung tissue of pulmonary fibrosis model and NaHS group in each time point were significantly lower than those of pulmonary fibrosis group(P<0.01,P<0.05).TGF-β1 was correlated positively with CTGF in each time point of every group(r = 0.891 ~ 0.968,all P<0.01).Conclusions Exogenous hydrogen sulfide ameliorates bleomycin-in- duced pulmonary fibrosis in rats through downregulation CTGF via inhibiting the TGF-β1 signal path.

关 键 词：硫化氢 肺纤维化 转化生长因子-1 结缔组织生长因子 

分 类 号：R965[医药卫生—药理学]