Resveratrol Attenuates Endoplasmic Reticulum Stress And Alveolar Epithelial Apoptosis In COPD Rats

Object:To explore alveolar epithelial cell apoptosis induced by endoplasmic reticulum stress in rats model of chronic obstructive pulmonary disease and the protection of resveratrol.Methods:48male Sprague-Dawley rats were completely randomly divided into four groups (N=12in each group), COPD group received intratraeheal instillation of lipopolysaccharide (LPS)200ug/100ul twice and exposured to cigarette smoke daily for two months, vehicle gavage; COPD+Res group received Resveratrol treatment (25mg/kg.d, gavage); control group received saline instead of LPS and vehicle gavage without cigarette smoke exposure; Res group received Resveratrol treatment (25mg/kg.d, gavage) and saline intratraeheal instillation. The spirometry was conducted and the lung pathological changes were observed, the protein expression of CHOP and active-Caspasel2were detected by immunohistochemistry and western blot, alveolar epithelial apoptosis wered analyzed by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). Data were expressed as means±SEM. Statistical analysis were carried out by one way analysis of variance followed by LSD multiple comparison tests.P<0.05were considered statistically significant.Results:1. The FEV0.3/FVC (%) and dynamic lung compliance (Cdyn) of the COPD rats were significant lower than those of the control rats with the airway resistance increased obviously (P<0.05), with the treatment of resveratrol, the FEV0.3/FVC (%) and Cdyn of the COPD+Res group rats were significant improved compared with COPD rats and RI decreased (P<0.05).2. Compared with the control group, significant small airway inflammation and emphysema were seen in COPD rats lungs, significant improvement could been seen when compared COPD+Res group with COPD group.3. In HIC, the main immune positive cell types were alveolar epithelia cell and macrophage cell, the COPD rats lung tissue Integrated Optical Density (IOD) of CHOP and Caspase12increased significantly Compared with the control group (P<0.05), while the IODs of COPD+Res group decreased significantly compared with COPD group (P<0.05).4. AS Western-blot results show, the protein expressions of CHOP、active-Caspase12increased in COPD group compared with control group, the ratios of CHOP/β-actin、active-Caspase12/β-actin were significantly higher than those of control group (P<0.05); with Res interference, the ratios of the COPD+Res group decreased significantly compared with COPD group (P<0.05).5. Higher Apoptosis index (AI) were seen in COPD group compared control group (P<0.05), represented more alveolar epithelial apoptosis, the AI decreased respectively in COPD+Res group compared with COPD group.Conclusions:there were endoplasmic reticulum stress induced apoptosis of pulmonary parenchyma cells especially alveolar epithelial cells in COPD rats, Resveratrol alleviates endoplasmic reticulum stress and attenuates alveolar epithelial apoptosis.