诱导性低温对失血性休克大鼠肝脏PGC-1和SHP表达的影响  

Effects of inducible hypothermia on expressions of PGC-1 and SHP in rat model of hemorrhagic shock

作　　者：张成[1] 高广荣[1] 李达[1] 单永琪[1] 张雪峰[1] 

机构地区：[1]沈阳军区总医院普通外科,沈阳110840

出　　处：《中华急诊医学杂志》2017年第2期186-190,共5页Chinese Journal of Emergency Medicine

基　　金：全军“十二五”医药卫生科研基金课题（CWS12J055）;辽宁省自然科学基金（2013020218）

摘　　要：目的探讨诱导性低温对失血性休克大鼠肝脏PGC-1和SHP表达的影响。方法SD大鼠随机（随机数字法）分为：对照组、低温组和常温组。按25ml／kg放血建立失血性休克模型，放血后分别维持大鼠直肠温度在32℃和38℃，休克60min后回输放出的血和2倍放血量的林格液，复苏期维持60min，复苏结束后恢复大鼠体温到38℃，监测血流动力学3h。记录建模前及建模后不同时点的血细胞压积（Hct）、乳酸（Lac）、剩余碱（BE）和血糖（Glu）。采用蛋白印迹及定量PCR的方法检测复苏3h后肝组织PGC-1和SHP蛋白及mRNA表达的变化。采用SPSS11．0软件包行计量资料的成组t检验。结果休克模型建立后血乳酸升高（0．9±0．2）m（8．3±1．8）、剩余碱减少（-3．2±1．1）135．（-7．4±3．3），与常温复苏比较，低温复苏可以显著降低血乳酸（6．3±2．1）US．（10．4±1．5）并增加碱剩余（-4．7±2．5）vs．（-9．0±3．2）。常温组动物的病死率较低温组明显增加。常温复苏可以上调PGC-1和SHPmRNA的表达（6．2±0．6）vs．（2．3±0．9），低温复苏导致PGC-1mRNA的表达下调（-2．2±0．4），但进一步增加了SHPmRNA的表达（7．4±1．3）。常温复苏3h后，PGC-1蛋白表达减少（0．39±0．13）vs．（0．24±0．12），而SHP蛋白表达增加（0．22±0．11）vs．（0．55±0．15）；低温复苏后PGC-1蛋白表达进一步减少（0．39±0．13）vs．（0．18±0．11），而SHP蛋白表达增加更加明显（0．22±0．11）vs．（1．02±0．21）。结论诱导性低温可以对PGC-1和SHP基因表达进行适应性调节，进而改善酸中毒和能量代谢失衡。Objective To investigate the effects of inducible hypothermia on expressions of peroxisome proliferator activated receptor gamma coactivator-1 （PGC-1） and small heterodimer partner （SHP） in rat model of hemorrhagic shock. Methods SD rats were randomly （random number） divided into three groups： control （C）, normothermia （N） and hypothermia （H）. Exsanguination was carried out in rats by continuously drawing out venous blood （25 mL/kg） over 15 minutes to establish hemorrhagic shock model. Then, rectal temperatures of rats were maintained by body surface cooling to 32℃ in H group and by body surface warming to 38℃ in N group, respectively. After a shock period of 60 minutes, rats received the infusion of whole blood of their own and lactated Ringer＇s solution （ 1 ： 2） treatment for 60 min, Rats were warmed to 38℃ by body surface warming and monitored for 3 h after resuscitation. Hematocrit （Hct）, base excess （BE）, lactate （Lac）, and glucose （Glu） were recorded before modeling and after different lengths of hemorrhagic shock period （HSP）. The expressions of PGC-1 mRNA and SHP mRNA and the levels of their protein in liver were tested by real-time reverse transcription polymerase chain reaction （qRT-PCR） and western blotting, respectively. Results The H group had lower lactate levels and higher BE levels than the N group [ （6.3±2. 1） vs. （10.4 ±1.5） and （ -4.7 ±2.5） vs. （ -9.0 ±3.2）] （P〈 0.05）. At 72 hours after modeling, there were four survivors in the N group and seven survivors in the H group （ P 〈 0.05, Log Rank）. The expressions of PGC-1 mRNA and SHP mRNA increased in N group. Hypothermia resuseitation down-regulated PGC-1 mRNA expression, meanwhile, increased expression of SHP mRNA. Both Hypothermia and Normothermia resuscitation increased SHP protein levels, but decreased PGC-1 protein levels. Conclusions Indueible hypothermia ameliorated aeidosis and energy metabolism imbalancethrough adaptive regulation in PGC-1

关 键 词：失血性休克 诱导性低温 PGC-1 SHP 蛋白印迹 PCR 大鼠 肝脏 

分 类 号：R459.7[医药卫生—急诊医学]