急进高原缺氧对大鼠肝脏孕烷X受体表达的影响

Effects of acute hypoxia on expression of pregnane X receptor in liver tissues of rats exposed to high altitude

目的:研究急进高原缺氧环境对大鼠肝脏孕烷X受体(PXR)表达的影响及相关机制。方法:Wistar雄性大鼠40只,随机分为对照组和急进高原缺氧12、24、36、48 h组,每组8只。待预定缺氧时间完成,采集各组大鼠腹主动脉血,全自动血气分析仪进行血气分析;HE染色观察肝组织病理变化状况;实时定量PCR测定各组大鼠肝组织中PXR mRNA水平;蛋白质印迹法测定各组大鼠肝组织中PXR和蛋白酶SUG1的表达。结果:与对照组比较,急进高原缺氧12 h后大鼠血液酸碱度值降低;缺氧24 h后动脉血氧饱和度(SaO 2)低于80%,动脉氧分压(PaO 2)低于60 mmHg(1 mmHg=0.133 kPa);缺氧48 h后动脉二氧化碳分压(PaCO 2)增加(P<0.05)。对照组大鼠肝组织结构完整,急进高原缺氧12、24 h组肝组织中央静脉有明显水肿,缺氧36、48 h组大鼠肝组织见炎性浸润。大鼠肝脏内PXR mRNA表达从急进高原缺氧12 h时即显著下调,缺氧12、24、36、48 h组分别降低了63%、96%、86%、85%(均P<0.05);其蛋白表达从缺氧36 h后显著上调,缺氧36、48 h后分别上调93%、99%(均P<0.05)。蛋白酶SUG1的表达从缺氧24 h开始降低,缺氧24、36、48 h后分别下降14%、34%、46%(均P<0.01)。结论:急进高原缺氧可对大鼠肝脏中核受体PXR表达产生影响,蛋白酶SUG1可能是影响急进高原缺氧下PXR表达的调控因素。

Objective:To investigate the effects of high-altitude hypoxic environment on the expression of pregnane X receptor(PXR)in rat liver and related mechanism.Methods:Wistar rats were randomly divided into five groups with 8 rats in each group,the rats were exposed to high-plateau hypoxia for 0(control group),12,24,36 and 48 h,respectively.Abdominal aortic blood samples were collected for blood gas analysis.HE staining was used to observe the pathological changes of liver tissue.The expression levels of PXR mRNA in liver tissues were determined by RT-PCR.Western blot analysis was performed to determine the protein expression of PXR and protease SUG1 in liver tissues of rats.Results:Compared with the control group,the blood pH of the rats decreased after 12 h of acute hypoxia.After 24 h exposed to hypoxia,SaO 2 was lower than 80%,PaO 2 was lower than 60 mmHg(1 mmHg=0.133 kPa);and PaCO 2 increased after 48 h exposed to hypoxia(P<0.05).There was obvious edema in the central vein of the liver tissue at 12 h and 24 h after exposure to hypoxia.The liver tissue of the rats exposed to hypoxia for 36 h and 48 h showed inflammatory infiltration.The expression of PXR mRNA was significantly decreased by 63%,96%,86%,and 85%at 12,24,36 h,and 48 h after exposure to hypoxia(all P<0.05),respectively.The protein expression of PXR was significantly up-regulated by 93%and 99%after 36 h and 48 h exposure to hypoxia(all P<0.05),respectively.The protein expression of proteinase SUG1 decreased by 14%,34%and 46%after 24,36 and 48 h after hypoxia(all P<0.01).Conclusion:Acute hypoxia at high altitude can affect the expression of nuclear receptor PXR in rat liver,and protease SUG1 may be a regulatory factor for PXR expression in hypoxia.