紫檀茋减轻百草枯诱导的模型大鼠肺纤维化

Pterostilbene reduces paraquat-induced pulmonary fibrosis in rat model

目的探究紫檀茋(Pte)减轻百草枯(PQ)诱导大鼠肺纤维化的作用及机制。方法将大鼠随机分为对照(control)组,PQ组(1次性灌胃50 mg/kg百草枯),低、中、高剂量Pte干预组(灌胃PQ 30 min后分别灌胃25、50和100 mg/kg Pte。每天1次,共7 d。)。治疗7 d后,用苏木精-伊红(HE)染色评价肺组织形态,用Masson三色染色评价肺纤维化。ELISA检测支气管肺泡灌洗液(BALF)中IL-1β、IL-6和MIP-2水平。用试剂盒检测肺组织中MDA和SOD含量。Western blot检测肺组织中E-cadherin、α-SMA、vimentin、Nrf2、NF-κB p65、p-NF-κB p65、TGF-β1、Smad3和p-Smad3的蛋白表达。结果与对照组比较,PQ组大鼠肺组织损伤程度,肺纤维化评分,BALF中的IL-1β、IL-6和MIP-2水平,肺组织中MDA含量,α-SMA、vimentin和TGF-β1的蛋白表达水平,NF-κB p65和Smad3蛋白的磷酸化水平均显著升高(P<0.05),而肺组织中SOD含量,E-cadherin和Nrf2的蛋白表达水平均显著降低(P<0.05)。Pte干预后,与PQ组比较,Pte组大鼠肺组织损伤程度,肺纤维化评分,BALF中的IL-1β、IL-6和MIP-2水平,肺组织中MDA含量,α-SMA、vimentin和TGF-β1的蛋白表达水平,NF-κB p65和Smad3蛋白的磷酸化水平均显著回降(P<0.05),而肺组织中SOD含量,E-cadherin和Nrf2的蛋白表达水平均显著回升(P<0.05)。结论紫檀茋可能通过激活Nrf2和抑制NF-κB和TGF-β1/Smad2/3信号通路减轻肺部氧化应激和炎性反应,从而抑制纤维化进展。

Objective To investigate the effect and mechanism of pterostilbene(Pte)on paraquat(PQ)-induced pulmonary fibrosis in rats.Methods The rats were randomly divided into control group,PQ group(intragastric administration of 50 mg/kg paraquat at one time),and low,medium and high dose of Pte intervention group(after 30 minutes of intragastric administration of PQ,25,50 and 100 mg/kg Pte were administered respectively.Once a day for 7 days).After 7 days of treatment,the morphology of lung tissue was evaluated by hematoxylin-eosin(HE)staining microscopy and pulmonary fibrosis was evaluated by Masson trichrome staining.The level of IL-1β,IL-6 and MIP-2 in bronchoalveolar lavage fluid(BALF)was determined by ELISA.MDA and SOD contents in lung tissues were detected with commercially available kit.The protein expression of E-cadherin,α-SMA,vimentin,Nrf2,NF-κB p65,NF-κB p65,TGF-β1,Smad3 and p-Smad3 in lung tissue was detected by Western blot.Results Compared with the control group,the injury degree of lung tissue,the score of pulmonary fibrosis,the level of IL-1β,IL-6 and MIP-2 in BALF,the content of MDA in lung tissue,the protein expression ofα-SMA,vimentin and TGF-β1 and the phosphorylation level of NF-κB p65 and Smad3 protein in lung tissue were all significantly increased in PQ group(P<0.05),while the content of SOD and the protein expression of E-cadherin and Nrf2 in lung tissue were significantly decreased(P<0.05).After Pte intervention,the injury of lung tissue,the score of pulmonary fibrosis,the level of IL-1β,IL-6 and MIP-2 in BALF,the content of MDA in lung tissue,the protein expression ofα-SMA,vimentin and TGF-β1 and the phosphorylation of NF-κB p65 and Smad3 protein in lung tissue were all significantly decreased in Pte group(P<0.05),while the content of SOD and the protein expression of E-cadherin and Nrf2 in lung tissue were significantly increased(P<0.05).Conclusions Pterostilbene may inhibit fibrosis progression by reducing oxidative stress and decrease of inflammatory response in the lung through activation of Nrf2 and inhibition of NF-κB and TGF-β1/Smad2/3 signaling pathways.