摘要:
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°C in H group and by body surface warming to 38°C 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°C 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 BElevels 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 resuscitation 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 Inducible hypothermia ameliorated acidosis and energy metabolism imbalance through adaptive regulation in PGC-1 and SHP.%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25 ml/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°C和38°C,休克60 min后回输放出的血和2倍放血量的林格液,复苏期维持60 min,复苏结束后恢复大鼠体温到38°C,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SPSS 11.0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)vs.(8.3±1.8)、剩余碱减少(-3.2±1.1)vs.(-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)vs.(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SHP mRNA的表达(6.2±0.6)vs.(2.3±0.9),低温复苏导致PGC-1 mRNA的表达下调(-2.2±0.4),但进一步增加了SHP mRNA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.