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

作　　者：裴毓华[1] 扬春松[1] 丁佑铭[2] 

机构地区：[1]江汉大学实验师范学院生物教研室,武汉430070 [2]武汉大学人民医院外科

出　　处：《肿瘤防治研究》2006年第10期723-725,共3页Cancer Research on Prevention and Treatment

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。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 28 days after intratracheal instillation. Histological changes of the lung tissue was evaluated by HE stain and collagen content was assessed by hydroxyproline concentration. The contents of NO2^-/ NO3^- （nitrite/nitrate） and ET-1 in plasma and lung tissue were detected. Results In the development of pulmonary fibrosis,the level of NO2^-/ NO3^- and ET-1 in plsama and lung tissue were upregulated. The high level of NO and ET-1 in lung could be reversed by ARK In addition, ARB significantly reduced the total lung hydroxyproline in BLM rats. Conclusion Losartan alleviates bleomyclin-induced pulmonary fibrosis in rats. Inhibiting the production of NO and ET-1 in lung tissues may be one of the mechanisms.

关 键 词：氯沙坦 肺纤维化 博莱霉素 一氧化氮 内皮素-1 

分 类 号：R73-35[医药卫生—肿瘤] R521.6[医药卫生—临床医学]