红景天苷对支气管肺炎大鼠Nrf2/Keap1通路及气道炎症的影响

Effects of salidroside on Nrf2/Keap1 pathway and airway inflammation in rats with bronchopneumonia

目的通过构建支气管肺炎SD大鼠实验模型,探究红景天苷对支气管肺炎大鼠核因子红细胞相关因子2(Nrf2)/Kelch样环氧氯丙烷相关蛋白(Keap1)通路及气道炎症的影响。方法将SD大鼠随机分为对照组、模型组及红景天苷低、高剂量(30、60 mg/kg)组和鸦胆子苦醇组,红景天苷+鸦胆子苦醇组,每组10只。红景天苷组大鼠分别ip 30、60 mg/kg红景天苷,鸦胆子苦醇组大鼠ip 100 mg/mL鸦胆子苦醇,红景天苷+鸦胆子苦醇组ip 60 mg/kg红景天苷和100 mg/mL鸦胆子苦醇。对照组使用同等剂量生理盐水。取各组大鼠肺泡灌洗液,对灌洗液中嗜酸性粒细胞、中性粒细胞和淋巴细胞数量进行分类和计数,ELISA法检测肺泡灌洗液中白细胞介素-1β(IL-1β)、白细胞介素-13(IL-13)、白细胞介素-18(IL-18)水平。苏木精–伊红(HE)染色法观测各组大鼠肺组织形态,Western blotting法检测大鼠肺组织IL-1β、诱导型一氧化氮合酶(iNOS)及Nrf2/Keap1信号通道相关蛋白表达水平。结果与模型组相比,红景天苷30、60 mg/kg组大鼠肺泡灌洗液中嗜酸性粒细胞、中性粒细胞和淋巴细胞数量,IL-1β、IL-13、IL-18水平及肺组织IL-1β、iNOS、Keap1蛋白表达、炎症评分显著降低,肺组织Nrf2蛋白表达水平显著升高(P<0.05);与红景天苷60 mg/kg组相比,红景天苷+鸦胆子苦醇组大鼠肺泡灌洗液中嗜酸性粒细胞、中性粒细胞和淋巴细胞数量,肺泡灌洗液IL-1β、IL-13、IL-18水平,肺组织IL-1β、iNOS、Keap1蛋白表达水平,炎症评分显著升高,肺组织Nrf2蛋白表达水平显著降低(P<0.05)。结论红景天苷可能通过激活Nrf2/Keap1信号通道缓解支气管肺炎炎症。

Objective To explore the effects of salidroside on Nrf2/Keap1 pathway and airway inflammation in rats with bronchopneumonia by constructing an experimental model of SD rats.Methods SD rats were randomly divided into control group,model group,salidroside low and high dose(30 and 60 mg/kg)groups,Brusatol group,salidroside+Brusatol group,with 10 rats in each group.Salidroside group rats ip 30 and 60 mg/kg salidroside,Brusatol group rats ip 100 mg/mL Brusatol,salidroside+Brusatol group ip 60 mg/kg salidroside and 100 mg/mL Brusatol,respectively.The control group received the same dose of normal saline.The numbers of eosinophils,neutrophils,and lymphocytes in the lavage fluid were classified and counted.The levels of IL-1β,IL-13,and IL-18 in the lavage fluid were detected by ELISA.The morphology of lung tissue was observed by hematoxylin and eosin(HE)staining.The expression levels of IL-1β,iNOS,and Nrf2/Keap1 signaling channel related proteins in lung tissue were detected by Western blotting.Results Compared with the model group,the numbers of eosinophils,neutrophils,and lymphocytes in the alveolar lavage fluid,the levels of IL-1β,IL-13 and IL-18,the protein expressions of IL-1β,iNOS and Keap1 in lung tissue,and the inflammation score of the salidroside 30 and 60 mg/kg groups were significantly decreased,the protein expression level of Nrf2 was significantly increased(P<0.05).Compared with salidroside 60 mg/kg group,the number of eosinophils,neutrophils,and lymphocytes in alveolar lavage fluid,the levels of IL-1β,IL-13 and IL-18 in alveolar lavage fluid,the protein expression levels of IL-1β,iNOS and Keap1 in lung tissue,and inflammation score of rats in salidroside+Brusatol group were significantly increased,the protein expression level of Nrf2 was significantly decreased(P<0.05).Conclusion Salidroside may alleviate the inflammation of bronchopneumonia by activating the Nrf2/Keap1 signal pathway.