Study On Protection Mechanism For Lungs Of Rats With Chronic Obstructive Pulmonary Disease By Doxofylline

Part-?Effect of doxofylline on inflammatory response in rat model of chronic obstructive pulmonary disease.Objective Airway inflammation is one of the most important pathogenesis of chronic obstructive pulmonary disease.Tumor Necrosis Factor??TNF-??and Interleukin 10?IL-10?are involved in the inflammatory reaction process in patients with chronic obstructive pulmonary disease.Our group aims to illuminate the regulatory role and related molecular mechanisms of airway inflammation in rats with chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide?LPS?.Methods Forty male SD rats were randomly divided into two groups,control group?C group??n=10?and test group?n=30?.Rats in the test group were placed in a smoke exposure chamber containing cigarette smoke produced by 3 ignited unfiltered cigarettes for 30 minutes every day for 2 months.200?g of LPS was injected into trachea only in the first and 30^th day.Rats in control group were kept under normoxia for 2 months,and the same volume of normal saline was injected into trachea in the first and 30^th day.Rats in test group were randomly and averagely divided into model group?M group?,model+saline group?M+NS group?and model+doxofylline group?M+D group?,respectively.Two months later,rats in each group were anesthetized,intubated with tracheal intubation and mechanically ventilated.Simultaneously,rats in model+doxofylline group were given intravenous injection of doxofylline 50 mg/kg,while rats in control group and model+saline group were given intravenous injection of saline of the same volume as rats in model+doxofylline group.After 2 hours of mechanical ventilation,the lung tissue of all rats was taken for testing of Wet/Dry Weight Ratio?W/D?and pathological examination.The TNF-?and IL-10 levels were detected by ELISA while the expression levels of c-jun-n-terminal kinase/stress-activated protein kinase?JNK/SAPK?and p-JNK were detected by Western blot and immunohistochemistry.Results Compared with the control group,pathological HE staining results of lung tissue of test groups showed typical chronic obstructive pulmonary changes,and the W/D,TNF-?,JNK and p-JNK level of those were significantly increased?P<0.05?,while the IL-10 level of which were significantly decreased?P<0.05?.Compared with the model group,there was no significant change in all of the detected indicators of the lung tissue in the model+saline group?P>0.05?.Compared with the model+saline group,the W/D,TNF-?,JNK and p-JNK level in the lung tissue of the model+doxofylline group were significantly lower?P<0.05?,and the IL-10 level in the lung tissue was significantly higher?P<0.05?.Conclusion In the rat model of chronic obstructive pulmonary disease induced by cigarette smoke and LPS,the TNF-?,JNK/SAPK signal pathway-mediated inflammatory response pathway is activated,and its inflammatory effects are inhibited by doxofylline;whereas the IL-10-mediated anti-inflammatory effect is inhibited but recover to some extent after administration of doxofylline.Part-? Effect of Doxofylline on Oxidative Stress Response in Rat Model of Chronic Obstructive Pulmonary DiseaseObjective Oxidative stress is one of the important pathogenesis of chronic obstructive pulmonary disease.To observe the regulation and related molecular mechanisms of doxofylline on airway oxidative stress response in rats with chronic obstructive pulmonary disease induced by cigarette smoke and LPS.Methods Rat grouping,modeling process,drug intervention method and the method of lung tissue extraction were the same to those in the first part.Malonaldehyde?MDA?and superoxide dismutase?SOD?level were detected by the corresponding molecular detection kits.Results Compared with the control group,the MDA levels of the lung tissue of rats in the test groups were significantly increased?P<0.05?,while the SOD levels of which were significantly decreased?P<0.05?.Compared with the model group,there was no significant change in the levels of MDA and SOD in the lung tissue of the model + saline group?P>0.05?.Compared with the model + saline group,the levels of MDA in the lung tissue of the model + doxofylline group were significantly lower?P<0.05?,and the level of SOD in the lung tissue was significantly higher?P<0.05?.Conclusion In the rat model of chronic obstructive pulmonary disease induced by cigarette smoke and LPS,the oxidative stress response pathway mediated by MDA is activated,and its effect can be inhibited by doxofylline;while antioxidant stress mediated by SOD in which is inhibited but partly recover after administration of doxofylline.