过氧化物酶增殖体激活受体β对失血性休克大鼠急性肺损伤的保护作用

Protective effects of peroxisome proliferation activated receptor-β on hemorrhagic shock - induced acute lung injury in rats

目的观察过氧化物酶增殖体激活受体β对失血性休克大鼠急性肺损伤的保护作用及机制。方法复制失血性休克大鼠ALI模型，随机（随机数字法）将96只SD大鼠分为5组，每组分为1h、2h、4h、6h四个时相点，每个时相点6只老鼠。观察记录在1、2、4、6h取肺组织测定PPARβ受体表达，行病理学检查、肺干湿重比系数作为检测肺损伤程度的指标；检测肺组织超氧化物酶SOD、GSH-Px活性氧化产物8-iso-PGF2α含量来评估机体氧化应激状态。然后，给予PPARβ受体拮抗剂（GSK0660）进行预处理，观察其对失血性休克所致急性肺损伤过程中后动物各项指标的影响，并初步探讨炎症因子、氧化抗氧化系统及细胞凋亡在其中的作用。结果①失血性休克致伤组大鼠超氧化物酶SOD、GSH—Px活性较假手术组显著升高（P〈0．01）。②GW0742激活剂使ALI肺组织中超氧化物酶SOD、GSH—Px活性在各时相点较单纯失血性休克致伤组有不同程度降低，以2h、4h升高最显著（P〈0．01）。③单独使用GW0742能改善PaO2、大鼠肺组织W／D比值、肺组织病理积分，抑制肺组织SOD、GSH—Px活性（P〈0．01）及降低8-iso-PGF2α的含量；使用拮抗剂GSK0660使上述作用减轻（P〈0．01）。结论①失血性休克ALI大鼠模型，肺组织SOD、GSH—Px活性显著升高，提示失血性休克处于急性氧化应激状态。②GW0742能显著上调Au大鼠肺组织SOD、GSH-Px的活性，降低氧化产物8一iso—PGF20t的含量。③推测GW0742通过可能通过抑制TNF—d基因和蛋白的表达，降低肺组织SOD活性对ALI肺组织起到一定程度的保护作用，减轻ALI肺组织的炎症，改善PaO2，可能是通过阻止NF-κB的活化起作用的。

Objective To observe the protective effects of peroxisome proliferation activated receptor- β（PPAR-b） on acute lung injury in the wake of hemorrhagic shock in rats in order to illuminate the mechanism. Methods After ALl model of rat was established following hemorrhagic shock, 96 SD rats were divided randomly （random number） into 4 groups： group A （sham operation group）, group B （ALI group）, group C （GSKO66O, an antagonist to PPAR-b given prior to exsanguinations for pretreatment） and group D （ GwO742, an agonist of PPAR-b given before exsanguinations for pretreatment）. Each group was further divided into 1 h, 2 h, 4 h and 6 h subgroups. Six mice of each subgroup were sacrificed at each interval. Expression of PPAR-13 receptor in lung tissues was detected at 1 h, 2 h, 4 h and 6 hours. Pathological examination and lung wet/dry weight ratio were detected, and lung tissue antioxidant enzyme SOD and 8-iso-PGF2a, the oxidation product of activated GSH-Px were evaluated. Results①Antioxidant enzymes SOD and activated GSH-Px were significantly higher in ALI group than those in the sham operation group （P〈O. O1）. ②he antioxidant enzyme SOD and activated GSH-Px in lung tissue in GWO742 group decreased at each interval especially at 2 h and 4 h compared with ALl group （P 〈O. O1 ）. ③GWO742 used alone can improvePaOz, W/D ratio of lung tissue of rats, lung pathology integral, and inhibit the activity of SOD and GSH-Px in lung tissue （P 〈O. O1 ） and decrease the content of 8-iso-PGF-2a. The antagonist GSKO66O can lessen the above effects （ P 〈 O. O1 ）. Conclusions.①ALI emerged from hemorrhagic shock in rats leading to significantly increased activity of SOD and GSH-Px in lung tissue, suggesting rats subjected to acute oxidative stress. ②GWO742 can up-regulate the levels of SOD and GSH-Px in lung tissue of rats with ALI. It also decreased the content of 8-iso-PGF2a the oxidation products of GSH-Px. ③ It was suggested that GWO742 might inhibit the expression of TNF-a mRNA and level of TNF-a protein, and decreased SOl） activity in lung tissue, protecting lung tissue to some degree from ALI and improving PaO2. The mechanism of it may be attributed to preventing NF-k B activation.