金荞麦提取物对百草枯中毒大鼠急性肺损伤和MAPK/NF-κB信号通路的影响  

Effects of Fagopyri Dibotryis Rhizoma extract on acute lung injury and MAPK/NF-κB signaling pathway in rats with paraquat poisoning

作　　者：陈永生 付斌[1] 郑永先[1] Chen Yongsheng;Fu Bin;Zheng Yongxian(Department of Emergency,Haikou People’s Hospital,Haikou Hainan 570208,China)

机构地区：[1]海口市人民医院急诊医学部,海南海口570208

出　　处：《遵义医科大学学报》2022年第6期736-742,共7页Journal of Zunyi Medical University

基　　金：海南省卫生健康行业科研项目(NO:20A200499)。

摘　　要：目的 探究金荞麦(FDR)提取物对百草枯(PQ)中毒大鼠急性肺损伤和丝裂原活化蛋白激酶(MAPK)/核因子κB(NF-κB)信号通路的影响。方法 将60只SD大鼠随机分为模型组(n=10)、阳性对照组(腹腔注射地塞米松2.5 mg/kg,n=10)、FDR-L组(灌胃FDR提取物140 mg/kg,n=10)、FDR-M组(灌胃FDR提取物280 mg/kg,n=10)、FDR-H组(灌胃FDR提取物560 mg/kg,n=10)和正常组(n=10),一次性腹腔注射20%PQ水剂30 mg/kg建立百草枯中毒大鼠急性肺损伤模型,造模后,每日给药1次,连续给药3 d后,取颈动脉血,全自动血气分析仪检测氧分压(PaO_(2))和二氧化碳分压(PaCO_(2));ELISA法检测SOD活性与MDA、IL-1β、TNF-α水平;分离肺组织,HE染色观察肺组织病理学改变,Masson染色观察肺组织纤维化情况,免疫组化法检测CollagenⅠ、CollagenⅢ蛋白表达,Western blotting法检测肺组织中MAPK/NF-κB信号通路相关蛋白表达。结果 与正常组比较,模型组大鼠PaO_(2)、SOD活性下降,PaCO_(2)、MDA、IL-1β、TNF-α水平以及肺组织中CollagenⅠ、CollagenⅢ、p-ERK/ERK、p-JNK/JNK、p-p38MAPK/p38MAPK、p-NF-κB/NF-κB表达升高(P<0.05);肺病变严重,中性粒细胞大量浸润,可见大量病灶,肺明显纤维化,肺损伤评分升高(P<0.05)。与模型组比较,阳性对照组与FDR提取物各剂量组肺病变减轻,肺纤维化程度减轻;PaO_(2)、SOD活性升高,PaCO_(2)、MDA、IL-1β、TNF-α水平以及肺组织中CollagenⅠ、CollagenⅢ、p-ERK/ERK、p-JNK/JNK、p-p38MAPK/p38MAPK、p-NF-κB/NF-κB表达降低(P<0.05),且各剂量组间具有剂量效应。与阳性对照组比较,FDR-H组上述指标差异无统计学意义(P>0.05)。结论 FDR提取物可抑制MAPK/NF-κB信号通路的激活,减轻氧化应激和炎症反应,改善肺纤维化,保护百草枯肺损伤。Objective To investigate the effects of Fagopyri Dibotryis Rhizoma extract(FDR) on acute lung injury and mitogen-activated protein kinase(MAPK)/nuclear factor κB(NF-κB) signaling pathway in rats poisoned by paraquat.Methods Sixty SD rats were randomly divided into normal,model,positive control(dexamethasone 2.5 mg/kg,ip),FDR-L(FDR 140 mg/kg,ig),FDR-M(FDR 280 mg/kg,ig),and FDR-H(FDR 560 mg/kg,ig)groups,10 rats each group.A single dose of paraquat(30 mg/kg,ip) was injected to produce lung injury model,followed by FDR treatment for 3 days.Carotid blood was collected,and the partial pressure of oxygen(PaO_(2)) and carbon dioxide(PaCO_(2)) were measured by automatic blood gas analyzer.SOD activity and MDA,IL-1β,TNF-α levels were detected by ELISA;Pathological changes of lung tissue were observed by HE staining,the fibrosis of lung tissue was observed by Masson staining.Collagen-Ⅰ and Collagen-Ⅲ protein expression were detected by immunohistochemistry.The expression of MAPK/NF-κB signaling pathway-related proteins was detected by Western blotting.Results Compared with the normal group,the activities of PaO_(2) and SOD in the Model group were significantly decreased,the levels of PaCO_(2),MDA,IL-1β and TNF-α,the expression of Collagen-Ⅰ,Collagen-Ⅲ and p-ERK/ERK,p-JNK/JNK,p-p38 MAPK/p38 MAPK and p-NF-κB/NF-κB in lung tissue were increased(P<0.05);the lung was severely damaged by paraquat,the alveoli were massively destroyed,the alveolar wall was thickened,neutrophil infiltration and lung fibrosis were evident,and the lung tissue damage score was increased(P<0.05).FDR extract and dexamethasone treatments ameliorated paraquat-induced lung pathological lesions;the PaO_(2) and activities of SOD were significantly increased,the levels of PaCO_(2),MDA,IL-1β and TNF-α,the expression of Collagen-Ⅰ,Collagen-Ⅲ and p-ERK/ERK,p-JNK/JNK,p-p38 MAPK/p38 MAPK and p-NF-κB/NF-κB in lung tissue were decreased(P<0.05).There was a dose-dependent effect among FDR groups,and the protection of FDR-H group was comparable

关 键 词：金荞麦提取物 丝裂原活化蛋白激酶 核因子ΚB 百草枯 中毒 急性肺损伤 

分 类 号：R963[医药卫生—微生物与生化药学]