茵陈蒿汤调控Nrf-2/HO-1通路对慢性阻塞性肺疾病大鼠气道重塑的影响OACSTPCD
Effect of Yinchenhao decoction on airway remodeling in rats with chronic obstructive pulmonary disease by regulating the Nrf-2/HO-1 pathway
目的:探讨茵陈蒿汤调控抗氧化相关转录因子核因子相关因子 2(Nrf-2)/亚铁血红素氧化酶 1(HO-1)通路对慢性阻塞性肺疾病(COPD)大鼠气道重塑的影响.方法:通过注射脂多糖联合烟熏制备 COPD大鼠,造模后随机分为模型组、茵陈蒿汤(4.41 g/kg)组、氨茶碱(2.3 mg/kg)组、茵陈蒿汤+抑制剂(4.41 g/kg茵陈蒿汤+30 mg/kg ML385)组,并以正常大鼠为对照组,检测大鼠肺功能[呼气峰流量(PEF)、第一秒用力呼气容积(FEV1)/用力肺活量(FVC)];评估血清白细胞介素(IL)-1β、IL-6 水平及肺组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平;检测肺组织病理学变化以及转化生长因子(TGF-β)、结缔组织生长因子(CTGF)阳性表达、金属基质蛋白酶(MMP)-2 mRNA、MMP-9 mRNA 表达、Nrf-2、H O-1 蛋白表达.结果:模型组 FEV1/FVC、PEF、肺组织 SOD、GSH-Px水平、Nrf-2、H O-1 蛋白表达较对照组降低,血清 IL-1β、IL-6、病理评分、肺组织 TGF-β、CTGF、MMP-2 mRNA、MMP-9 mRNA表达增加(均P<0.05);茵陈蒿汤或氨茶碱治疗后,FEV1/FVC、PEF、肺组织 SOD、GSH-Px水平、Nrf-2、HO-1 蛋白表达较模型组增加,血清 IL-1β、IL-6、病理评分、肺组织 TGF-β、CTGF、MMP-2 mRNA、MMP-9 mRNA表达显著降低(均P<0.05);茵陈蒿汤联合 ML385 治疗后,FEV1/FVC、PEF、肺组织 SOD、GSH-Px水平、Nrf-2、HO-1 蛋白表达较茵陈蒿汤组降低,血清 IL-1β、IL-6、病理评分、肺组织 TGF-β、CTGF、MMP-2 mRNA、MMP-9 mRNA表达增加(均P<0.05).结论:茵陈蒿汤可通过调控Nrf-2/HO-1 通路改善COPD大鼠气道重塑.
Objective:To investigate the effect of Yinchenhao decoction on airway remodeling in rats with chron-ic obstructive pulmonary disease(COPD)by regulating the nuclear factor erythroid2-related factor(Nrf-2)/heme oxygenase-1(HO-1)pathway.Methods:COPD rats were prepared by injecting lipopolysaccharide combined with smoking.After modeling,they were randomly separated into model group,Yinchenhao decoction(4.41 g/kg)group,aminophylline(2.3 mg/kg)group,Yinchenhao decoction+inhibitor(4.41 g/kg Yinchenhao decoction+30 mg/kg ML385)group,and normal rats were regarded as the reference group.Rat lung functions peak expiratory flow(PEF),first second forced expiratory volume(FEV1)/forced vital capacity(FVC)were measured.The levels of ser-um interleukin(IL)-1β,IL-6,lung tissue superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were evaluated.The pathological changes in lung tissue,the positive expression of transforming growth factor-β(TGF-β)and connective tissue growth factor(CTGF),the expression of metalloproteinase-2 mRNA and MMP-9 mRNA,and the expression of Nrf-2 and HO-1 proteins were detected.Results:The FEV1/FVC,PEF,levels of SOD,GSH-Px,and expression of Nrf-2 and HO-1 proteins in lung tissue in model group were greatly lower than reference group,the serum IL-1β,IL-6,pathological score,lung tissue TGF-β,CTGF,MMP-2 mRNA,and MMP-9 mRNA expression were greatly higher(all P<0.05).However,after treatment with Yinchenhao decoction or aminophylline,the levels of FEV1/FVC,PEF,SOD,GSH-Px,Nrf-2,and HO-1 proteins in lung tissue were greatly higher than model group,the serum IL-1β,IL-6,pathological score,lung tissue TGF-β,CTGF,MMP-2 mRNA,and MMP-9 mRNA expression were greatly lower(all P<0.05).After Yinchenhao decoction+ML385 treatment,FEV1/FVC,PEF,SOD,GSH-Px levels in lung tissue,Nrf-2,and HO-1 protein expression were greatly lower than Yinchenhao decoction group,the se-rum IL-1β,IL-6,pathological score,lung tissue TGF-β,CTGF,MMP-2 mRNA,and MMP-9 mRNA expression were greatly higher(all P<0.05).Conclusion:Yinchenhao decoction improves airway remodeling in COPD rats by regula-ting the Nrf-2/HO-1 pathway.
李春晓;李怀臣
山东中医药大学,山东 济南 250013
临床医学
慢性阻塞性肺疾病茵陈蒿汤Nrf-2/HO-1通路气道重塑炎性反应氧化应激
Chronic obstructive pulmonary diseaseYinchenhao decoctionNrf-2/HO-1 pathwayAirway re-modelingInflammatory responseOxidative stress
《陕西中医》 2024 (008)
1031-1035,1041 / 6
山东省自然科学基金资助项目(ZR2020KH013)
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