摘要
目的观察阻断肾素-血管紧张素-醛固酮系统不同环节对大鼠肺纤维化模型的干预作用,并探讨其作用机制。方法SD大鼠气管内注入博莱霉素复制肺纤维化模型,随即分别每日胃管内灌注生理盐水(B组)、卡托普利60 mg/kg(C组)、氯沙坦10 mg/kg(L组)、螺内酯100 mg/kg(S组)进行干预,正常对照组(N组)气管和胃管内灌注均以生理盐水代替。各组动物均于给药后第7、14、28天分别随机处死5只,通过HE染色、Masson胶原染色及测定肺组织羟脯氨酸浓度来评价治疗效果。用免疫组化法和图像分析系统定量检测肺组织单核细胞趋化蛋白-1(MCP-1)的表达。结果(1)C组、S组、L组肺泡炎和肺纤维化程度、MCP-1的蛋白表达均显著低于B组,且3种药物作用无明显差别。(2)测定肺组织HYP含量发现,3种药物作用差异显著。结论卡托普利、螺内酯、氯沙坦均能减轻博莱霉素诱导的大鼠肺纤维化,这种作用可能部分通过抑制MCP-1的表达而实现。对于减轻肺组织胶原的堆积,3种药物中螺内酯最优,氯沙坦最差。
Objective To study the effects on puhnonary fibrosis in rats after the blockage of the rennin - angiotensin - aldosterone system at different sites and its mechanism. Methods Pulmonary fibrosis was induced ir Sprague- Dawley（SD） rats by intratracheal instillation of bleomycin. Then the rats were perfused into stomach daily normal saline （group B）, captopril 60 mg/kg （group C）, losartan 10 mg/kg （group L）, spironolactone （group S）. Normal controls received normal saline both by intratracheal instillation and perfusion into stomach. Five rats in each group were sacrificed on 7, 14, 28 days respectively after intratracheal instillation. Histological changes of the lungs were evaluated by HE stain, Masson＇s trichrome stain and hydroxyproline concentration of the lung tissue. The expression of monoeyte chemoattractant protein- 1 （MCP- 1）was measured by immunhistochemical method with image analyse system. Results （1） The level of lung fibrosis and alveolitis, positive rate of MCP - 1 of lung tissues in rats of group C, S, L were significant lower than that in rats of group B, and the effects of the three drugs had no significant differences. （3）The effects of the three drugs had significant differences in hydroxyproline concentration of the lung tissue. Conclusion Captopril, spironolactone, losartan can all allevieate bleomycin - induced pulmonary fibrosis in rats. Inhibiting the expressions of MCP - 1 in lung tissues may be one of the mechanisms. The effect of spironolactone to reduce collagen content in lung tissues was the best, and the effect of losartan was the worst in the three drugs .
出处
《南华大学学报（医学版）》
2007年第2期186-188,191,共4页
Journal of Nanhua University(Medical Edition)
基金
衡阳市科技局研究项目基金资助(编号06kj13)
