多烯磷脂酰胆碱通过过氧化物酶体增殖物激活受体γ保护脓毒症大鼠

Protective effects of polyenylphosphatidylcholine on rat septic model through peroxisome proliferator activated receptor γ

目的探讨多烯磷脂酰胆碱（PPC）对大鼠脓毒症模型的保护作用及其机制。方法利用大鼠盲肠结扎穿孔（CLP）模型建立大鼠脓毒症模型。将75只SD雄性大鼠随机分为假手术（Sham）组、PPC对照（Sham—PPC）组、脓毒症（CLP）组、PPC保护（CLP-PPC）组、过氧化物酶体增殖物激活受体1（PPARγ）拮抗（CLP—PPC／GW9662）组。另外两组大鼠观察CLP组与CLP-PPC组脓毒症建立后7d生存率。模型建立18h后测量血流动力学指标、血糖（GLU）、动脉血气、谷丙转氨酶（ALT）、谷草转氨酶（AST）、一氧化氮（NO）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子（TNF）一d水平及肝脏湿／干重比（W／D）。结果脓毒症建立7d后，CLP组仅有4（4／20）只大鼠存活，而CLP—PPC组有12（12／20）只大鼠存活。PPC能够纠正脓毒症休克状态，显著改善血流动力学指标（P〈0．01）。CLP—PPC组肝脏炎症损伤较CLP组轻，W／D、ALT、AST、LAC、TNF-α、NO和MDA水平显著降低，SOD活力及血糖显著升高，差异有统计学意义（P〈0．05）。静脉注射PPC前给予GW9662，能够阻断PPC对脓毒症大鼠的保护作用。结论预保护应用PPC能够显著降低脓毒症大鼠肝脏炎症反应，改善肝代谢功能，纠正感染性休克。PPC对脓毒症大鼠的抗炎保护作用与PPARγ有关。

Objective To investigate the protective effects of polyenylphosphatidylcholine （PPC） in rat cecal ligation and puncture （CLP） model and the underlying mechanisms. Methods Prospective, randomized and controlled animal study was performed. Seventy-five male Sprague-Dawley rats were randomly divided into five groups by using random number table： sham group, sham-PPC group, CLP group, CLP-PPC group, and CLP-PPC/GW9662 group in which peroxisome proliferator activated receptor γ （PPARγ） antagonist GW9662 was administrated before the pretreatment of PPC in CLP rats. The 7-day survival of CLP group and CLP-PPC group was monitored after the introduction of sepsis. The rats were subjected to sepsis by CLP. The hemodynamic parameters of all animals were recorded 18 h after the surgery and the samples were collected. The arterial blood gas was analyzed, and the levels of liver wet/dry ratio （ W/D）, aspartate aminotransferase （ AST）, alanine aminotransferase （ ALT）, nitric oxide （ NO）, superoxidase dismutase （SOD）, malondialdehyde （MDA） and tumor necrosis factor （TNF）-oL in serum were determined. Results Seven days after CLP, there were only 4 （4/20） rats left in CLP group while 12 （12/20） rats survived in CLP-PPC group. PPC could reverse the hypodynamic collapse in sepsis （P 〈 0. 01 ）. As compared with CLP group, the rats in CLP-PPC group showed less severe hepatic inflammation. The levels of W/D, ALT, AST, TNF-α, NO, MDA and LAC were significantly lower in CLP-PPC group while blood glucose and the activity of SOD were significantly increased （P 〈 0. 05）. GW9662 blocked the protective effects of PPC in sepsis. Conclusion Intravenous administration of PPC before the onset of sepsis may alleviate hepatic injury in sepsis, improve liver functions and reverse septic shock. PPC exerts its protective influence on rat sepsis model partially through PPARγ.