阻断肾素血管紧张素醛固酮系统不同位点对百草枯中毒大鼠肺纤维化的影响

Effect on paraquat-induced pulmonary fibrosis in rats after blockage of the rennin-angiotensin-aldosterone system at different sites

目的观察通过药物阻断肾素血管紧张素醛固酮系统的不同位点对百草枯中毒大鼠肺纤维化的影响及探讨可能的作用机制。方法 SD大鼠一次性百草枯80mg/kg灌胃建立肺纤维化模型,分别每日胃管内灌注生理盐水(染毒组)、卡托普利60mg/kg、氯沙坦10mg/kg和螺内酯100mg/kg进行干预。对照组以生理盐水灌胃。各组大鼠均于染毒后第7、14、28d分批处死,取肺组织行苏木素―伊红(HE)与Masson染色并行肺泡炎、肺纤维化评分,测肺羟脯氨酸(Hyp)含量,用免疫组化法和图像半定量分析系统检测肺组织结缔组织生长因子(CTGF)蛋白的表达。结果各干预组各时间点大鼠肺泡炎和肺纤维化程度积分、肺Hyp含量、肺组织CTGF蛋白的表达均低于染毒组(P<0.01)。3组采用药物干预后,肺Hyp含量比较的差异有统计学意义(P<0.05)。结论卡托普利、氯沙坦与螺内酯均能减轻百草枯中毒大鼠肺纤维化的程度,可能通过阻断不同的受体抑制CTGF蛋白的表达而实现。螺内酯减轻肺组织胶原沉积的疗效最佳,氯沙坦最差。

Objective To observe effects on paraquat-induced pulmonary fibrosis in rats after blockage of the rennin-an- giotensin-aldosterone system at different sites by different drugs and to explore possible mechanisms. Methods Pulmonary fibrosis model was established by paraquat poisoning in SD rats by one-hit intragastrically with PQ 80 mg/kg. Then the rats were perfused into stomach and treated with daily normsaline （PQ group）, captopril （60 mg/kg）, losartan （10 mg/kg）, spironolactone （100 mg/kg）. Cotrol group received normal saline by perfusion into stomach. The rats in each group were sacrificed and lungs were harvested on each 7, 14 or 28 d respectively. The degrees of pulmonary alveolitis and fibrosis were evaluated by HE staining and Masson Staining. Hydroxyproline （Hyp） concentration were detected and levels of protein expression of connective tissue growth factor （CTGF） of lung tissues were determined by immunohistochemistry staining with semquantitative picture analyse system. Results The scores of pulmonary alveolitis and fibrosis, hydroxyproline concentrations and the protein positive expression of CTGF of lung tissues in rats of each interfere group were significant lower than those in PQ group （P〈0.01）. The effects of three drugs on hydroxyproline concentrations had significant differences （P〈0.05）. Conclusion Captopril, losartan and spironolactone can all alleviate levels of pulmonary fibrosis caused by paraquat poisoning in rats, which may be due to inhibition of different receptors and protein expressions of CTGF. The effect of spironolactone to reduce collagen content in lung tissues was the best and effect of losartan was the worst.