麻黄、五味子联用地塞米松对肺纤维化大鼠血管新生促进因子与抑制因子的影响

目的探讨麻黄、五味子联用地塞米松(DXM)对肺纤维化大鼠血管新生促进因子与抑制因子的影响。方法将106只SPF级雄性Wistar大鼠随机分成假手术组、模型组、麻黄组、五味子组、麻黄+DXM组、五味子+DXM组以及DXM组。采用气管滴入博莱霉素(7 mg/kg)法复制肺纤维化模型,并分别给予相应的药物干预。各组大鼠分别于造模后第7天、第28天腹主动脉取血处死,肺组织灌洗后HE染色观察病理形态变化,ELISA法检测血清中缺氧诱发因子(HIF)-1α、血小板衍生生长因子(PDGF)、色素上皮源性因子(PEDF)和内皮抑素endostatin的表达水平。结果模型组HIF-1α、PDGF、PEDF和endostatin的表达升高,与假手术组比较具有显著性差异(P0.01);第28天时HIF-1α、PDGF含量较第7天时升高,PEDF和endostatin含量较第7天时降低。与模型组比较,麻黄组、五味子组HIF-1α、PDGF表达降低,PEDF、endostatin表达升高(P0.05);麻黄组第28天与第7天比较,HIF-1α、PDGF表达升高,PEDF、endostatin表达降低。五味子组与麻黄组情况相反。第7天、第28天,麻黄+DXM组、五味子+DXM组与模型组比较,HIF-1α、PDGF表达降低,PEDF、endostatin表达升高(P0.05);第7天、第28天比较表达无显著变化。与DXM组比较,五味子+DXM组HIF-1α表达升高,PEDF表达降低,具有显著性差异(P0.05)。结论肺纤维化进程中血管新生调控因子失去平衡,麻黄、五味子可抑制HIF-1α、PDGF的表达,促进PEDF、endostatin表达,与地塞米松联用后,对肺纤维化的不同病理阶段选择性减弱。

Effects of Herba Ephedra and Fructus Schisandrae combined with dexam-ethasone on angiogenic factors and inhibitors in rats with idiopathic pul-monary fibrosis

Objective To observe the effects of Mahuang ( Herba Ephedra ) and Wuweizi ( Fructus Schisandrae) combined with dexamethasone ( DXM) on expression of angiogenic factors and inhibitors in rats with idiopathic pulmonary fibrosis ( IPF) .Methods Wistar male rats of SPF level ( n=106 ) were divided randomly into sham operation group , model group, Mahuang group, Wuweizi group, Mahuang+DXM group , Wuweizi+DXM group and DXM group .The model of IPF was established by using instilla-tion of bleomycin (7 mg/kg) except for the sham operation group .Each group was administered intra-gastrically of corresponding drug .All rats were sacrificed on the 7th and 28th day via abdominal aorta blood-letting, and the pathological changes of lung tissue were evaluated with HE staining and the expres -sion of hypoxia-inducible factors 1α( HIF-1α) , platelet derived growth factor ( PDGF) , pigment epitheli-um-derived factor ( PEDF) and endostatin in rat serum were also measured with ELISA .Results Com-pared with the sham operation group , the expression of HIF-1α,PDGF, PEDF and endostatin in model group significantly increased (P<0.01);the HIF-1αcontent on the 28th day was higher than that on the 7th day, and the PEDF and endostatin content were lower than that on the 7th day.The expression of HIF-1αand PDGF significantly decreased in Mahuang group and Wuweizi group compared with the model group, and the expression of PEDF and endostatin increased (P<0.05).Compared with Mahuang group on the 28th day,the expression of HIF-1αand PDGF on the 7th day increased markedly, but the expres-sion of PEDF and endostatin on the 28th day was lower than those on the 7th day.In the Wuweizi group the changes in the expression of HIF-1α,PDGF, PEDF and endostatin were opposite to Mahuang group.The expression of HIF-1αand PDGF significantly decreased in Mahuang+DXM group and Wuweizi+DXM group compared with the model group ( P<0 .05 ) , and the expression of PEDF and endostatin increased . In Wuweizi+DXM group the HIF-1αcontent was significantly higher than those in DXM group while the PEDF content was significantly lower ( P<0.05 ) .Conclusion Regulatory factors on angiogenesis lose their balance in rats with IPF .Mahuang and Wuweizi could achieve inhibition of the expression of HIF-1αand PDGF, and selectively promote the expression of PEDF and endostatin .When combined with DXM, the selectivity might be weakened in different pathological stages .