The protective effect of rosiglitazone on the rats with high altitude pulmonary edema

Abstract

Objective To investigate the protective effect of rosiglitazone on the rats with high altitude pulmonary edema. Methods Thirty-six SD rats were randomly(random number) divided into 6 groups(n=6 each): control group(Control), hypobaric hypoxia model group(HH), rosiglitazone groups(RSG)which were administered with 3 different doses[RSG-L: 5 mg/(kg·d), RSG-M: 10 mg/(kg·d), RSG-H: 20 mg/(kg·d) ], dexamethasone group[Dex, 4 mg/(kg·d)]. Rats were injected intraperitoneally with different doses of rosiglitazone (RSG), dexamethasone(Dex)or vehicle (Control and HH) for 3 days before placed in simulated altitude of 6 000 m hypobaric hypoxia animal chamber where the temperature and pressure were constant. After 72 h in the chamber, each rat was anesthetized.The water content of lung was determined with wet/dry weight ratio. Bronchoalveolar lavage fluid was measured by bradford method. The contents of GSH was measured by micro-ezymed labeled method. The contents of MDA was measured by TBA method. The enzymatic activities of SOD was measured by WST-1 method.The changes of the TNF-α, IL-6 and IL-10 in serum were determined by ELISA.Light microscope was used to observe the pathological changes of lung tissue. Results Compared with Control group, the wet/dry weight ratio of lung(5.08±0.24) and total protein content of BALF(351.06±44.55)μg/mL increased significantly (P<0.01) in HH group. There were red blood cells in the alveolar and interstitium, pink fluid exudation in the alveolar, the alveolar septum enhancement, and a large number of inflammatory cell infiltration; the SOD activity(10.65±0.94)U/mgprot and the content of GSH(1.63±0.20)μmol/gprot in lung tissue were significantly decreased (P<0.01), the contents of MDA(2.15±0.18)nmol/mgprot increased significantly (P<0.01), TNF-α(56.92±2.87)pg/mL and IL-6(217.80±48.01)pg/mL levels in serum were significantly increased (P<0.01), and IL-10(76.85±16.72)pg/mL level decreased (P<0.05). Compared with the HH group, the wet/dry ratio of lung and total protein content of BALF in different doses of rosiglitazone group significantly decreased (P<0.01), the pathological changes of the lung tissue was significantly improved, SOD activity and the content of GSH in lung tissue was significantly increased (P<0.01), the content of MDA decreased (P<0.01), The levels of TNF-α and IL-6 in serum were significantly decreased (P<0.01), while the IL-10 level was significantly increased (P<0.01). Conclusion Rosiglitazone could protect the high altitude pulmonary edema by alleviating the oxidative stress and inflammatory response. Key words: Rosiglitazone; High altitude pulmonary edema; Oxidative stress; Inflammation; Rat