益气化瘀化痰法对肺纤维化大鼠TGF-β1、PAI-1的影响

摘要

Objective To evaluate the effects of therapeutics of benefiting qi, expelling blood stasis and dissipating phlegm on transforming growth factor-β1 (TGF-β1 )and plasminogen activator inhibitor-1 (PAI-1) of rats with pulmonary fibrosis. Methods We built the model of pulmonary fibrosis in rats by disposable endotracheal injection of bleomycin 5 mg/kg. 105 SD rats were divid-ed into 7 groups, including normal group, model group, the benefiting qi group, the expelling blood stasis group, the dissipating phlegm group,the benefiting qi, expelling blood stasis and dissipating phlegm group, hormone group. Normal control group and model group were lavaged with normal saline,hormone group was given subcutaneous injection of hydrocortisone 20 mg · kg-1 ,the rest groups were lavaged with corresponding medicines 30 g · kg-1· d-1 (the benefiting qi decoction,the expelling blood stasis decoction, the dissipating phlegm decoction, the benefiting qi, expelling blood stasis and dissipating phlegm decoction) separately for 28 d after pulmonary fibrosis models were established. All rats were killed after 2 months interventing treatment. We measured plasma PAI-1 levels in each group by ELISA,and detected the lung tissue expression of TGF-β1 protein by Western blot. Results PAI-1 contents in plasma of rats in the benefiting qi group,the expelling blood stasis group,the dissipating phlegm group,the bene-fiting qi,expelling blood stasis and dissipating phlegm group were lower than those of the model group(P<0. 05) , especially the benefiting qi,expelling blood stasis and dissipating phlegm group reduced most obviously(P<0. 05). TGF-β1 protein expressions in the benefiting qi group, the expelling blood stasis group, the dissipating phlegm group, the benefiting qi, expelling blood stasis and dissipating phlegm group were weakener than those in the model group(P<0. 05) ,the benefiting qi,expelling blood stasis and dis-sipating phlegm group weakened most obviously(P<0. 05). Conclusion The therapeutics of benefiting qi, expelling blood stasis and dissipating phlegm can significantly inhibit bleomycin-induced pulmonary fibrosis in rats,and the possible mechanism was by in-hibiting TGF-β1 and PAI-1 expression in the fibrotic process.%目的 探讨益气化瘀化痰法对肺纤维化大鼠肺组织转化生长因子-β1(TGF-β1)及纤溶酶原激活物抑制物-1(PAI-1)的影响.方法 采用气管内一次性注射博来霉素5 mg/kg诱导生成肺纤维化大鼠模型.将105只SD大鼠分为:正常对照组、模型组、益气组、化瘀组、化痰组、益气化瘀化痰组、激素组.正常对照组和模型组采用生理盐水灌胃,其余各组于造模后28 d分别给予益气汤、化瘀汤、化痰汤、益气化瘀化痰汤30 g·kg-1·d-1灌胃,激素组给予皮下注射氢化可的松20 mg·kg-1·d-1干预,2个月后处死各组大鼠,ELISA法检测各组大鼠血浆PAI-1含量,Western blot法检测各组大鼠肺组织TGF-β1蛋白表达.结果 益气组、化瘀组、化痰组及益气化瘀化痰组大鼠血浆PAI-1含量水平较模型组均降低(P<0.05),其中益气化瘀化痰组降低最显著(P<0.05);益气组、化瘀组、化痰组及益气化瘀化痰组大鼠肺组织TGF-β1蛋白表达较模型组均减弱(P<0.05),尤以益气化瘀化痰组减弱最明显(P<0.05).结论 益气、化瘀、化痰法能显著改善博来霉素所致大鼠肺纤维化的程度,其机制可能与抑制TGF-β1及PAI-1的表达有关.