氯沙坦对肺纤维化大鼠一氧化氮和内皮素-1合成的影响

Effect of Losartan on Nitric Oxide and Endothelin-1 in the Development of Blomycin-induced Pulmonary Fibrosis in Rats

摘要: 目的观察肺脏一氧化氮(NO)和内皮素-1(ET-1)在抗肿瘤药物博莱霉素(BLM)所致大鼠肺间质纤维化过程中的动态变化,探讨氯沙坦对大鼠肺纤维化模型的影响及其作用机制。方法45只Wistar大鼠随机分为空白组、模型组和氯沙坦治疗组,气管内灌注BLM造成肺纤维化模型,灌注次日开始灌胃给药。观察各组动物肺脏病理组织学改变、血浆及肺组织中NO2-/NO3-、ET-1含量、肺组织羟脯氨酸含量的变化。结果肺组织及血浆中NO2-/NO3-含量在气管灌注BLM后迅速上升,第14天达高峰(与空白组相比,P<0.01),于第28天基本恢复正常。肺中ET-1水平也明显升高(与空白组相比,P<0.01)。氯沙坦能显著降低肺中NO、ET-1的升高,延缓肺纤维化的发展。结论NO和ET-1在BLM所致肺间质纤维化的发生发展中起重要作用,氯沙坦能通过抑制NO、ET-1的产生达到治疗肺纤维化的目的。

Abstract: Objective To observe the alteration of nitric oxide,Endothelin-1 in the development of blomycin-induced pulmonary fibrosis in rats and the effect of Losartan on this model. Methods Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin (5mg/kg body weight).Then the rats received daily Losartan 10 mg/kg(group L) or sterile saline (group B) orally.Normal controls (group C) received sterile saline both intratracheally and orally.Five rats in each group were sacrificed 7,14,and ...