罗格列酮对肺纤维化大鼠肺动脉壁结缔组织生长因子表达的影响

Effects of rosiglitazone on the expression of connective tissue growth factor in the pulmonary arteries of rats suffering from fibrosis in lung

目的:观察过氧化物酶体增殖活化受体γ(PPAR-γ)激动剂罗格列酮(RSG)对肺纤维化大鼠肺动脉壁结缔组织生长因子(CTGF)上调、Ⅰ型和Ⅲ型胶原沉积的影响。方法:48只雄性SD大鼠,随机分为以下4组:博莱霉素(BLM)+生理盐水(NS)组(n=21)、BLM+RSG组(n=9)、NS+NS组(n=9)和NS+RSG组(n=9)。气管内一次性滴注BLM(5mg/kgbw),RSG灌胃(3mg/(kg.d),14d)。整体实验,气管滴注后第14天观察;离体实验,气管滴注BLM后第14天,分离大鼠的肺动脉,并用RSG培养液和单纯培养液孵育(37℃,5%CO2,24h)。结果:在整体水平,与对照大鼠相比,BLM模型大鼠肺动脉壁的CTGF免疫阳性表达增强,CTGF蛋白含量、Ⅰ型和Ⅲ型胶原含量、Ⅰ/Ⅲ胶原比值均增高(均P<0.05);RSG能阻止上述指标的异常变化(均P<0.05);在离体水平,RSG能阻止BLM模型大鼠肺动脉壁CTGF的上调(P<0.05),但对Ⅰ型和Ⅲ型胶原沉积无明显影响(P>0.05)。结论:RSG能直接作用于肺动脉壁,阻止肺纤维化大鼠肺动脉壁CTGF的上调,这可能是其减轻动脉壁结构重塑的机制之一。

Objective：To explore the effects of rosiglitazone（RSG）,an agonist of peroxisome proliferators-activated receptor-γ（ PPAR-γ）,on the up-regulation of connective tissue growth factor（CTGF） and the deposition of type Ⅰand type Ⅲ collagens in the pulmonary arteries of rats suffering from fibrosis in lung.Methods：Forty-eight male Sprague-Dawley rats were randomly divided into 4 groups：bleomycin （BLM） plus normal saline（NS） group（n=21）,BLM plus RSG group（n=9）,NS plus NS group（n=9）,and NS plus RSG group （n=9）.The rats were received single intratracheal instillation of BLM （5 mg/kg bw） or equal volume of NS as control,and received intra-gastric administration of RSG（3 mg/（kg·day）,14 day） or the same volume of NS as vehicle.In vivo,the observation was conducted on day 14 after intratracheal instillation.In vitro,the pulmonary arteries of rats on day 14 after BLM were isolated and incubated with DMEM alone or with RSG （37℃,5%CO2,for 24 h.Results：In vivo,the expression and the content of CTGF,the contents of type Ⅰand type Ⅲ collagens,and the ratio of typeⅠcollagen and type Ⅲ collagen were increased in the pulmonary arteries of BLM-instilled rats,compared with those of NS-instilled rats （All P0.05）.The above abnormal changes were ameliorated by RSG （All P0.05）.In vitro,RSG blocked the up-regulation of CTGF （P0.05）,but not the deposition of typeⅠcollagen and type Ⅲ collagen in the pulmonary arteries isolated from the BLM-instilled rats （P0.05）.Conclusion：The results suggest that RSG directly blocks the up-regulation of CTGF in pulmonary arteries of rats suffering from fibrosis in lung,and this might be one of the mechanisms underling the ameliorated pulmonary arterial remodeling by RSG.