泻肺汤对肺纤维化模型鼠肺组织病理形态变化及Fas/FasL蛋白表达的影响

Effect of Xiefei Decoction on the Pathological Changes of Lung Tissue and Fas/FasL Protein Expression in Rats with Pulmonary Fibrosis

目的观察泻肺汤对博莱霉素致肺纤维化模型鼠肺组织病理形态变化及Fas/FasL蛋白表达的影响。方法SPF级SD大鼠84只随机分为空白对照组,博来霉素模型对照组,泻肺汤低、中、高剂量组,醋酸泼尼松组,每组14只。除空白对照组外,其余各组采用气管滴注博莱霉素法制备肺纤维化大鼠模型,空白对照组气管内滴注等量生理盐水,造模24 h后,泻肺汤低、中、高剂量组灌胃泻肺汤(10,20,40 g·kg^-1·d^-1),醋酸泼尼松组灌胃醋酸泼尼松(1.8 mg·kg^-1·d^-1),空白对照组和博来霉素模型对照组用等体积生理盐水灌胃,第29天处死动物,HE染色法观察肺组织的病理形态变化,ELISA法测定各组大鼠细胞间黏附因子-1(intercellular cell adhesion molecule-1,ICAM-1)和血清结缔组织生长因子(connective tissue growth factor,CTGF)的含量,实时荧光定量PCR法测定各组大鼠肺组织Fas和FasL的基因表达,Western blotting检测各组大鼠肺组织Fas和FasL的蛋白表达。结果与博来霉素模型对照组相比,泻肺汤各剂量组血清ICAM-1和CTGF均显著降低,肺组织Fas和FasL的基因表达也均显著减弱(P<0.05或P<0.01);同时,泻肺汤中、高剂量组肺组织Fas和FasL的蛋白表达均显著减弱(P<0.05或P<0.01)。结论泻肺汤可降低ICAM-1、CTGF含量和Fas/FasL表达来显著改善博来霉素诱导的肺纤维化,表明泻肺汤对博来霉素诱导的大鼠纤维化改善与Fas/FasL凋亡通路有关。

OBJECTIVE To observe the effects of Xiefei decoction on the pathomor-phism changes of lung tissue and the expression of Fas protein and FasL protein in lung tissue of pulmonary fibrosis rats induced by bleomycin.METHODS Eighty-four SPF SD rats were randomly divided into blank control group,bleomycin model group,low,middle and high-dose Xiefei decoction treatment groups and prednisone group,14 rats in each group.Except for the blank control group,the remaining groups used tracheal instillation of bleomycin to prepare pulmonary fibrosis rat models.In the blank control group,an equal amount of saline was instilled into the trachea.After 24 h of modeling,Xiefei decoction was administered by gavage of Xiefei decoction(10,20,40 g·kg^-1·d^-1)in the low,medium and high dose groups,and by prednisone acetate in the prednisone acetate group(1.8 mg·kg^-1·d^-1),the blank control group and the bleomycin model control group were gavaged with equal volume of normal saline,and the animals were sacrificed on the 29th day.To observe the pathomorphism changes of lung tissue with HE,check the contents of ICAM-1 and CTGF in serum with ELISA,Fas gene,FasL gene in lung tissue was assessed by RT-PCR,and Fas protein,FasL protein in lung tissue was assessed by Western blotting.RESULTS Compared with the bleomycin model group,the contents of ICAM-1,CTGF and the gene expression of Fas,FasL were decreased significantly in all groups of Xiefei decoction(P<0.05 or P<0.01).Meantime,the protein expression of Fas,FasL were also decreased in middle-dose,high-dose group of Xiefei decoction(P<0.05 or P<0.01).CONCLUSION Pulmonary fibrosis is improved significantly after the Xiefei decoction treated,the levels of ICAM-1,CTGF and the expressions of Fas/FasL are both decreased.These data shows that Xiefei decoction ameliorate the pulmonary fibrosis induced by bleomycin and it is related to Fas/FasL apoptotic pathways.