PPARγ Receptor Agonist Rosiglitazone On Chronic Obstructive Pulmonary Disease In Rat Of Arachidonic Acid Metabolite Of The Regulation

Chronic obstructive pulmonary disease (COPD) is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs; features which do not change markedly over time. Chronic airway inflammation plays an important role in the process of COPD development and progress. Peroxisome proliferators -activated receptorsγ( PPARγ) is the ligand activated transcription factor of nuclear hormone receptor superfamily. Metabolites of arachidonic acid hydroxyl 15 - 20 carbon acid (15-hydroxy eicosatetranoic acid, 15-HETE) and 15 - d-PGJ2 with anti-inflammatory effects are the natural ligands of PPARγ. Our previous experiments has shown that PPARγagonist rosiglitazone has the preventive and therapeutic effects on the development and progress of rat COPD duplicated with inhalation of tobacco smoke and instillation of E. coli lipopolysaccharide, the mechanism may be associated with inhibition of chemokines excretion of macrophages and reduced function of neutrophiles. In this experiment the effects of rosiglitazone on the metabolism of arachidonic acid of rats with COPD were investigated, lipoxidase and nuclear factor -κB activation were detected.32 SD rats were randomly divided into four groups (1) the normal control group: the rats were not treated; (2) COPD model group: the rats were inhaled with tobacco smoke every day for 28 days and instilled intratracheally with E. coli lipopolysaccharide (Lipopolysaccharide, LPS) on day 1st and 14th. (3) rosiglitazone therapy groups: each rat of this group was given the rosiglitazone 0.02 mg, using the method of gavage before a day before tobacco smoke inhaled every day for 28 days,the other treatments were same as COPD model group. (4) rosiglitazone control groups: each rat of this group was given the rosiglitazone 0.02 mg, using the method of gavage every day for 28 days , the other treatments were same as the normal control group. All the rats were killed on the 29th day, then collected the right lung tissue and the left lung to be perfused with PBS. bronchoalveolar lavage fluid (BALF) was collected.The white blood cells in BALF were counted and classified in each group. The content of 15-lipoxygenase (15– LOX) in the lung tissue supernatant was measured with ELISA. The cells with NF-κB positive nuclea were counted with immunofluorescenc. The content of LTC, LTE,15 - hydroxy - 20 carbon acid (15-HETE) in the supernatant of lung tissue was measured by liquid chromatography.Experimental data was shown with mean±SD and dealed with SPSS11.5 statistical software, inter-group difference in comparison was dealed with single-factor analysis of variance (ANOVA) and the straight-line correlation analysis.The results are as follows:(1)The count of the white blood cell in BALF in each group (×105 / L) :The count of white blood cell in COPD group (90.38±4.07) was significantly higher than that of other three groups (P <0.01);the count in rosiglitazone therapy group (57.38±4.10) was significantly higher than that of the normal control and rosiglitazone control group (P <0.01), but lower than COPD group (P <0.01); there was no difference in the count of the white blood cell in BALF between the normal control and the rosiglitazone control group(P>0.05).(2) There was no significant statistical difference in the content of 15-LOX in the lung tissue supernatant by ELISA among any group (P>0.05).Although the content of 15-LOX in COPD group had the higher trend than that in rosiglitazone therapy group.(3) the NF-κB positive cells percentage by immunofluorescenc COPD group NF-κB nuclear staining positive cells percentage (37.38±5.10) in COPD group was significantly higher than that in the other three groups (P <0.01); NF-κB nuclear staining positive cells percentage in rosiglitazone therapy group (24.00±2.00) was significantly higher than that in the normal control and rosiglitazone control group (P <0.01) but lower than that in COPD group (P <0.01); There was no significant statistical difference in NF-κB nuclear staining positive cells percentage between the normal control group and rosiglitazone control group(P> 0.05).(4) There was no significant statistical difference in the content of LTC,LTE,15-HETE in the Supernatant of lung tissue By liquid chromatography(P>0.05).The results showed that rosiglitazone can inhibit the inflammation of rat COPD duplicated inhalation of tobacco smoke andinstillation of E. coli lipopolysaccharide, reduced the infiltration of the white blood, alleviate lung tissue damage. The mechanism may be associated with the transcription of proinflammatory mediators via inhibiting NF-κB, leading to inhibition of airway inflammation, oxidative stress and the increase of protease load caused by the activation of the inflammatory cells, delaying the development of COPD. Lipoxygenase pathway of metabolism of arachidonic acid has no significant changes.