创伤感染致多器官功能障碍综合征大鼠肝组织中肝X受体的表达

Expression of liver X receptor in the liver tissues of rat with multiple organ dysfunction syndrome induced by wound infection

目的研究创伤感染致MODS过程中孤核受体家族成员肝X受体的表达变化及对MODS演变过程中发生脂质代谢障碍的意义。方法建立创伤感染致MODS动物模型：Wistar大鼠100只，随机分为单纯创伤组（T组）和创伤感染序贯致MODS组（M组），每组50只。钳夹大鼠肢体，造成多发性闭合型骨折和广泛性软组织挫伤，M组12h后造成背部30％TBSAⅢ度烫伤，并在创面涂布绿脓杆菌。分别于创伤前、创伤后24、48、96、120h，每时相点10只动物，检测血浆内毒素（LPS）、谷丙转氨酶（ALT）、游离脂肪酸（FFA）、甘油三酯（TG）、高密度脂蛋白（HDL）、极低密度脂蛋白（VLDL），对所有计数数据作Y0检验，计量资料采用单因数方法分析。同时采用荧光实时定量RT-PCR检测肝X受体基因的表达变化。结果大鼠伤后血清ALT、LPS呈逐步上升趋势；FFA水平在伤后96h达到峰值（P〈0．05）；TG呈现先增高后降低的趋势，在伤后96h降至谷底；HDL呈逐步下降趋势；VLDL先降后升；对照组大鼠肝组织LXRα的基因表达在伤后24h先是出现小幅增强，此后表达明显下调，MODS组下降趋势更明显，并显著低于对照组。结论ALT伤后逐步增高，与血浆LPS趋势同步，呈显著正相关，表明感染直接加重了肝功能损害程度；LXRα基因在早期表达增高，后期下降，LPS同LXRα表达呈负相关，可能是引起LXRα变化的影响因素；肝脏LXRα基因在MODS期转录活性显著下降，结合血清FFA、TG、HDL、VLDL变化分析，可能导致胆固醇向肝内的转运和肝内脂肪酸的合成障碍。

Objective To study the expression of liver X receptor （LXR） during the progress of muhiple organ dysfunction syndrome （MODS） caused by wound infection, and its role in the lipid metabolism during MODS. Method The MODS models caused by wound infection were produced. One hundred Wistar rats were randomly divided into wound group （group T, n = 50） and MODS caused by wound infection group （group M, n = 50）. The closed multi-fracture and extensive soft-tissue injury was produced in rats using jaw. After 12 hours, a thirty percent total body surface area Ⅲ （TBSA Ⅲ） bum was induced in group M, and the rats were contaminated by pseudomonas aeruginosa. The levels of endotoxin （LPS）, alanine transaminase （ALT）, free fatty acid （FFA）, TG, HDL, VLDL were determined before injuries and post injuries 24, 48, 96, 120 hours, and at each time point in each group, only 10 rats were determined. And at the same time, real-time quantitative reverse transcription polymerase chain reaction technique was used to measure the gene expression of LXR. Chi-square test was used. Results The blood ALT and LPS levels in rats were increased slowly, the levels of FFA reached peak at 96 hours post injuries （P 〈 0.05）, the level of TG increased first and then decreased to the lowest at 96 hours, HDL dropped slowly, and VLDL decreased first and then increased. The gene expression of LXR increased slightly at 24 hours and then gradually decreased in group T, and the gene expression of LXR decreased more obviously in group M, and there was significant difference compared with group T. Conclusions ALT increased slowly, and was positively correlated with LPS post injuries. This indicated that infection aggravated the liver injury. The gene expression of LXRα increased in the early stage and then decreased in the late stage, LPS and LXPα were negatively correlated, which may cause the change of LXRα. The decreased expression of LXRα during MODS may contribute to dysfunction of cholesterol transport and fatty acid synthesis.