缬沙坦恢复哮喘大鼠气道肝细胞生长因子的生成及其意义

Effect of valsatan on hepatocyte growth factor in the airways of asthmatic rats

摘要:

目的：探讨血管紧张素受体拮抗剂(AT1)缬沙坦,对恢复哮喘大鼠气道肝细胞生长因子(HGF)的生成与哮喘气道重塑的关系和意义。方法：SD清洁级大鼠32只,体重在100±10g,随机分为4组:A组:正常对照组,B组:卵蛋白(OVA)激发2周组,C组:OVA激发4周组,D组:OVA激发4周后缬沙坦干预组。用免疫组化法测定各组大鼠气道的HGF,AngII和TGF-β1的表达变化,苏木精-伊红染色观察气道病理变化。结果：A组HGF较B组有明显差异[(5.49±1.34)%vs(10.69±0.96)%,P<0.05],C组为(11.85±0.87)%,较A组升高(P<0.05),D组为(15.58±1.06)%,较B组、C组升高。AngII和TGF-β1的表达则随着OVA激发时间的延长而增加,在使用缬沙坦后两者都明显下降。经抗原致敏和激活的大鼠气道上皮脱落炎性细胞堆积呈现明显的病理改变,而缬沙坦干预组的病理改变较轻,上皮细胞较完整,炎性细胞和纤维细胞较少。结论：①HGF随着气道重塑变化浓度有所改变,说明早期HGF即有保护气道作用,和TGF-β1呈负相关性,有拮抗纤维化的作用;②AT1可改善气道重塑过程,可能是通过升高气道HGF水平达到抗纤维化的作用。

Abstract:

OBJECTIVE: To study the effect of valsatan (angiotensin II receptor antagonist, AT1) on hepatocyte growth factor (HGF) in the airways and airway remodeling in asthmatic rats. METHODS: Thirty-two rats were randomly assigned into A-D four groups. Group A was normal control without treatment. Groups B-D were challenged by ovalbumin (OVA) for 2 weeks, 4 weeks and 4 weeks respectively to induce asthma. Group D received intragastric administration of valsatan (30 μg/kg daily for 4 weeks) after OVA challenge. The expressions of HGF, angiotonin II (AngII) and transforming growth factor (TGF-β_1) in the airways were detected by immunihistochemical staining. The pathological changes of airways were observed by Haematoxylin & Eosin staining. RESULTS: The HGF expression of Group B was significantly higher than that of Group A (10.69±0.96% vs 5.49±1.34%; P<0.05). Group C also showed an increased HGF level (11.85±0.87%) compared with Group A (P<0.05). The HGF level in Group D (15.58±1.06%) was significantly higer than that of both Group B and Group C (P<0.05). The expressions of TGF-β_1 and AngII increased with the challenged time, while valsatan treatment decreased significantly the levels of both. Valsatan treatment attenuated airway injuries of asthmatic rats induced by OVA sensitization/challenge. CONCLUSIONS: HGF has protective effects on airways and anti-fibrotic effects. Valsatan can improve airway remodeling possibly by increasing HGF levels in asthmatic rats.