关键词: 紫檀茋, 百草枯, 肺纤维化, 氧化应激, 炎性反应

Abstract: 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 of α-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 of α-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.

Key words: pterostilbene, paraquat, pulmonary fibrosis, oxidative stress, inflammation