儿茶素对慢性阻塞性肺疾病大鼠气道重塑和Nrf2/HO-1通路的影响OA

Aim:To explore the effect of catechin(Cat)on airway remodeling and nuclear factor E2 related factor 2/heme oxygenase-1(Nrf2/HO-1)pathway in rats with chronic obstructive pulmonary disease(COPD).Methods:A total of 75 COPD model rats were successfully established using a combination of smoke exposure and airway lipopolysaccharide in-jection,and were randomly allocated into COPD group,Cat-L,Cat-M,and Cat-H groups,and Cat-H+ML385 group,with 15 rats in each group.Fifteen rats without smoke exposure served as the control group.Cat-L,Cat-M,and Cat-H groups received Cat at doses of 0.7,1.4,and 2.8 mg/kg by gavage,respectively;the Cat-H+ML385 group received oral administration of 2.8 mg/kg Cat along with intraperitoneal injection of 30 mg/kg of ML385(Nrf2 inhibitor);the control group and COPD group were administered normal saline,once daily for 4 consecutive weeks.After the final administration,pulmonary function was assessed(n=15);HE staining was performed to observe pulmonary histopathological changes,and bronchial wall thick-ness as well as smooth muscle thickness were measured,immunohistochemical SP assay was used to detect the expression of transforming growth factor-1(TGF-β1)and α-smooth muscle actin(α-SMA)in lung tissue(n=5);corresponding kits were used to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),and matrix metalloproteinase tissue inhibitor-2(TIMP-2)in bronchoalveolar lav-age fluid(BALF)(n=5),the levels of SOD,malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in lung tissue were measured(n=5);Western blot was employed to quantify the expression of Nrf2 and HO-1 proteins in lung tissue(n=5).Results:Compared with the control group,COPD group exhibited significant pathological damage in lung tissue with ex-tensive inflammatory cell infiltration,and the inflammatory scores were(3.20±0.30);bronchial wall thickness,smooth muscle thickness,airway resistance(RI),TNF-α,IL-6,MMP-2,and MMP-9 concentrations in BALF,MDA,as well as TGF-β1 and α-SMA expression in lung tissue increased;peak expiratory flow rate(PEF),dynamic compliance(Cydn),TIMP-2 in BALF,SOD and GSH-Px in lung tissue as well as Nrf2 and HO-1 expression decreased(P<0.05).Compared with the COPD group,the 3 CaT groups demonstrated reduced pathological damage in lung tissue with lower inflammatory scores,bronchial wall thickness,smooth muscle thickness,RI,TNF-α,IL-6,MMP-2,and MMP-9 in BALF,lower MDA levels in lung tissue,and decreased TGF-β1 and α-SMA expression;concurrently,increased PEF,Cydn,TIMP-2 level in BALF,and elevated SOD,GSH-Px levels,and Nrf2 and HO-1 expression(P<0.05),exhibiting dose-dependent effects(P<0.05).In contrast to the Cat-H group,the Cat-H+ML385 group showed aggravated pathological damage in lung tissue,with opposite changes in all parameters(P<0.05).Conclusion:Cat may activate the Nrf2/HO-1 pathway to inhibit airway inflammation and oxidative stress,and improve airway remodeling in COPD rats.