肝细胞生长因子在哮喘大鼠气道内的表达及血管紧张素II受体拮抗剂对其表达的影响

Expression of hepatocyte growth factor and effect of angiotensin II receptor antagonist on asthmatic rats

目的探讨哮喘大鼠发病过程中,肝细胞生长因子(HGF)在其气道内表达的变化及血管紧张素II受体AT1拮抗剂对其表达的影响。方法清洁级SD大鼠48只,随机分为正常对照组、卵蛋白(OVA)激发3 d组、OVA激发2周组、OVA激发4周组、OVA激发4周后使用AT1受体拮抗剂组、OVA激发4周后使用盐水对照组。观察OVA激发的不同时间、药物干预后哮喘大鼠气道的病理改变;免疫组化方法观察HGF、血管紧张素II(AngII)、转化生长因子(TGF)-β1表达的变化。结果HGF在OVA激发3 d即明显高于正常对照组(P<0.05),OVA激发2周HGF在气道中的表达水平最高,OVA激发4周时下降;AngII、TGF-β1表达水平随OVA激发时间的延长而持续上升;使用AT1受体拮抗剂后,气道HGF表达水平有所上升,而AngII、TGF-β1均下降,同时哮喘大鼠的气道重塑有所改善。结论HGF在哮喘发病过程中起保护作用,AngII、TGF-β1对HGF具有负向调节作用,AT1受体拮抗剂在一定程度上可提升内源性HGF表达,改善哮喘大鼠的气道重塑。

Objective To study the expression of hepatocyte growth factor （HGF） in the asthmatic rat airway and to investigate the anti-asthmatic effect of angiotensin Ⅱ receptor（AT1 ） antagonist. Methods Forty-eight Sprague-Dawley rats were randomly divided into control group, three-day-ovalbumin（OVA）-chal- lenge group, two-week-OVA-challenge group, four-week-OVA-challenge group, OVA-AT1 antagonist group and OVA-saline group. Rat asthma model was established by intraperitoneal injection of 10 % ovalbumin （OVA） on day 1 and 14 and then challenged with inhalation of 1% OVA aerosol in normal saline for 20 min/ d for different days （3 days for three-day-OVA-challenge group, 2 weeks for two-week-OVA-challenge group, 4 weeks for four-week-OVA-challenge group）. OVA-AT1 antagonist group and OVA-saline group were treated with 4 weeks OVA challenge and then AT1 antagonist or normal saline for 4 weeks respectively. The airway pathological change was assessed and the expressions of HGF, transforming growth factor （TGF）-β1 and angiotensin Ⅱ（AngⅡ） were detected by using immunohistochemical method. Results Compared to the control group, HGF expression in airway increased significantly in three-day-OVA-challenge group（ P 〈 0.05 ）, peaked in two-week-OVA-challenge group, and declined in four-week-OVA-challenge group. The expression of AngII and TGF-β1 were increased as the OVA challenge time prolonged. After using AT1 antagonist, HGF expression increased again but the expressions of AngII and TGF-β1 decreased, suggesting the improved airway remodeling. Conclusion HGF has protective effect on the airway remodeling in asthma. AngⅡ and TGF-β1 can downregulate HGF expression. AT1 antagonist can enhance HGF level and improve airway remodeling by inhibiting the expression of AngII and TGF-β1.