The Effect And Mechanism Of Curcumin On Oxidative Stress And Inflammation In A Rat Model Of Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease(COPD)is a common disease which is preventable and treatable.Its main feature is incompletely reversible airflow limitation.According to the latest epidemiological survey,the morbidity of COPD among people over 40 years old in China is as high as 13.7%,which is 5.5%higher than 10 years ago.At present,there are nearly 100 million COPD patients in China.The morbidity and mortality of COPD are also on the rise worldwide,and it is expected that it will become the third leading cause of death in the world by 2030.The pathogenesis of COPD is complex and remains unclear.Although it is preventable and treatable,there is still lack of therapeutic drugs/methods to prevent progressive decline of lung function in clinic.Therefore,it has attracted worldwide attention to the prevention and treatment of COPD.Inflammation,oxidative stress and protease/antiprotease imbalance are the critical pathogenesis of COPD.Besides,COPD is also affected by both heredity and environment.Smoking and infection are the most important environmental factor,and smoking is also the riskest factor.Smoking causes oxidative stress,which promotes inflammation and reduces the sensitivity to hormone therapy.Antioxidant therapy maybe can alleviate and/or inhibit the progressive decline of lung function in COPD patients,which may change the course of COPD.Curcumin is a polyphenolic pigment extracted from the Curcuma longa(turmeric).Modern pharmacological studies have shown that curcumin possess great anti-oxidation property due to its unique molecular structure.Curcumin not only plays an important protective role in tobacco smoke-mediated oxidative stress,but also restores hormone sensitivity.The present study used exposure to cigarette smoking combined with intratracheal instillation of LPS to establish a rat of COPD model and investigated the effect and mechanism of curcumin on oxidative stress and inflammation in a COPD rat,which with the aim of finding new drugs or methods for the prevention and treatment of COPD.Objective:To evaluate the effect of curcumin on oxidative stress and inflammation in COPD rats and examine the mechanism.Methods:The rat model of COPD was established by exposure to cigarette smoking combined with intratracheal instillation of LPS.Thirty-six Male Sprague-Dawley rats were randomly divided into three groups:control group,copd group and curcumin(cur)group(12 rats per group).Rats in the control group received the same volume of sterile saline instead of LPS and were kept with free access to regular chow and water.After determined the lung function,rats were executed and blood,bronchoalveolar lavage fluid(BALF)and lung tissue were collected.The HE staining was applied to evaluate the histopathological changes of lung tissues.BALF and serum IL-8,TNF-α,MDA,SOD were assayed by ELISA.The protein and the mRNA level expression of Nrf2 and HO-1 were detected by immunohistochemistry,RT-PCR and Western blotting.Results:Compared with the control group,Ri,Re in the copd group were significantly increased,and the indexes of Cdyn,FEV0.3/FVC were significantly declined(all P<0.05).While,after treatment with curcumin,the lung function of COPD rat was improved(all P<0.05),besides,the serum and BALF IL-8,TNF-a,MDA were significantly reduced and SOD was significantly increased(all P<0.05).HE staining analytical results shown the pathological changes and the infiltration of inflammatory cell obviously in copd group.However,treatment with curcumin,the abnormal pathological injuries were ameliorated.Moreover,it is shown that the curcumin can exhibited higher Nrf2 and HO-1 protein and mRNA expression(all P<0.05).Conclusion:1.The rat model of COPD was successfully established by exposure to cigarette smoking combined with intratracheal instillation of LPS.Curcumin administration improved the lung function and reduced oxidative stress and inflammation,which suggested that curcumin exerts protective effects in COPD rat.2.The role of curcumin exerting anti-inflammatory and anti-oxidation effects in COPD rat may be related to the activation of Nrf2/HO-1 pathway.