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

Abstract

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 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. Key words: Hemorrhagic shock; Inducible hypothermia; Peroxisome proliferator activated receptor gamma coactivator-1; Small heterodimer partner; Western blotting; Real-time reverse transcription polymerase chain reaction; Rat; Liver