氨溴索在百草枯中毒大鼠肺纤维化中的保护作用

摘要

目的 研究盐酸氨溴索注射液(氨溴索)对百草枯(PQ)中毒肺纤维化的影响及相关机制.方法 将105只SD大鼠随机分为5组:正常对照组(NC组)、百草枯中毒组(PQ组)、氨溴索普通剂量治疗组(PN组)、氨溴索大剂量治疗组(PL组)、氨溴索超大剂量治疗组(PE组),采取腹腔注射法构建动物模型:NC组注射1.25 mg/kg生理盐水;PQ组注射25 mg/kg 2％PQ溶液;PN组注射25 mg/kg 2％PQ溶液+30 mg/(kg·d)氨溴索;PL组注射25 mg/kg 2％PQ溶液+50 mg/(kg·d)及PE组注射25 mg/kg 2％PQ溶液+90 mg/(kg·d).在模型建立后21 d处死动物,肺组织行HE和Masson染色分别观察炎症以及纤维化情况;ELISA法测定支气管肺泡灌洗液(BALF)中白介素-6(IL-6)含量,q-PCR和Western blot分别测定肺组织中组织金属蛋白酶抑制因子1(TIMP-1)和肿瘤坏死因子-α(TNF-α)mRNA和蛋白的表达.结果 NC组肺组织正常,百草枯模型组大鼠肺损伤和肺组织胶原沉积明显.各剂量氨溴索治疗均能显著减少百草枯中毒诱导的大鼠肺组织胶原沉积,同时伴有IL-6、TIMP-1和TNF-α表达的显著下降(P＜0.05).在氨溴索治疗各组中,与PN组相比,大剂量治疗和超大剂量治疗更能够抑制百草枯中毒诱导的大鼠肺纤维化(P＜0.05),降低肺组织IL-6、TIMP-1和TNF-α的表达(P＜0.05).结论 氨溴索可减轻大鼠百草枯中毒所致的肺纤维化,有望成为治疗百草枯中毒所致肺纤维化的有效方法.%Objective To investigate the effect of ambroxol on paraquat-induced pulmonary fibrosis in rats.Methods 105 SD rats were randomly divided into five groups,NC group treated with 1.25 mg/kg normal saline,PQ group treated with 25 mg/kg 2％ paraquat,PN group treated with 25 mg/kg 2％ paraquat+30 mg/(kg·d) ambroxol,PL group treated with 25mg/kg 2％ paraquat+50 mg/(kg·d) ambroxol,PE group treated with 25 mg/kg 2％ paraquat+90 mg/(kg·d) ambroxol.The rats were kiiled on 21 d after modeling,the degrees of acute pulmonary injury and fibrosis were detected by HE staining and Masson staining;the mRNA and protein expressions of TIMP-1 and TNF-αwere evaluated by real time qPCR and Western-blot respectively.Results The lung tissue was normal in NC group,while it showed that significant injury of lungs,fibrosis and large collagen deposition in PQ group.After ambroxol treatment,fibrosis and large collagen deposition reduced,expression of IL-6,TIMP 1-and TNF-o increased (P ＜ 0.05).Among ambroxol treatment group,compared with PN group,ambroxol at high or large dose could restrained more significantly Paraquat poisoning inducing fibrosis and large collagen deposition in rats (P ＜ 0.05),and reduced expression of IL-6,TIMP 1-and TNF-α (P ＜ 0.05).Conclusion Ambroxol treatment alleviates paraquat poisoning-induced lung fibrosis.Ambroxol might be a promising way to treat araquat poisoning-induced lung fibrosis.