罗格列酮对高原肺水肿大鼠的保护作用

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

目的探讨罗格列酮对高原肺水肿大鼠的保护作用。方法将36只sD大鼠随机（随机数字法）分为6组：对照组（Control）、低压低氧模型组（HH）、罗格列酮低剂量组[RSG—L，剂量为5mg／（kg·d）]、中剂量组[RSG-M，剂量为10ms／（kg·d）]、高剂量组[RSG—H，剂量为20mg／（kg·d）]、地塞米松组[Dex，剂量为4ms／（kg·d）]，每组6只。连续给药3d后，置于模拟海拔6000In低压低氧动物实验舱内，维持恒温恒湿，每24h给药1次。72h后，处死大鼠，用湿干质量比（W／D）法检测肺组织含水量，考马斯亮蓝法检测肺泡灌洗液（BALF）蛋白含量，微量酶标法测量肺组织中谷胱甘肽（GSH）含量，TBA法测量肺组织中丙二醛（MDA）含量，wsT-1法测量肺组织中超氧化物歧化酶（SOD）活性，ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、白介素-10（IL-10）含量。光镜观察肺组织病理变化。结果与Control组比较，HH组W／D（5．08±0．24）和BALF蛋白含量（351：06±44．55）μg／mL明显增加（P〈0．01），病理结果显示肺泡及肺间质内可见红细胞，肺泡内有粉红色液体渗出，肺间隔增宽明显，炎细胞浸润；肺组织SOD活性（10．65±0．94）U／mgprot、GSH含量（1．63±0．20）μmol／grpot显著降低（P〈0．01），MDA含量（2．15±0．18）nmol／mgprot明显升高（P〈0．01），血清TNF-d（56．92±2．87）pg／mL、IL-6（217．80±48．01）pg／mL水平明显增加（P〈0．01），而IL-10（76．85±16．72）pg/mL水平下降（P〈0．05）；与HH组比较，罗格列酮各剂量组W／D和BALF蛋白含量明显下降，肺组织病理改变明显改善，肺组织SOD活性、GSH含量明显升高（P〈0．01），MDA含量降低（P〈0．01），血清TNF-仅、IL-6水平明显下降（P〈0．01），而IL-10水平明显上升（P〈0．01）。结论罗格列酮通过抑制氧化应激，减少炎症因子释放，对高原肺水肿起到良好的保护作用。

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 hypoxi.a model group （HH）, rosiglitazone groups （RSG） which were administered with 3 different doses [RSG-L： 5 mg/ （kg-d）, RSG-M： 10 rag/ （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） orvehicle （ 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 〈 O. 01 ）, while the IL-10 level was significantly increased （P 〈 0. 01 ） . Conehmion Rosiglitazone could protect the high altitude pulmonary edema by alleviating the oxidative stress and inflammatory response.