| Object:To analyze the protection mechanism of propofol preconditioning on liver injury of exertional heat stroke rats. Methods:1. Construct exertional heat stroke (EHS), classic heat stroke (CHS) and running (R) rat models. We established EHS, CHS and R rat models by six computer-controlled multi-functional treadmill and enviromental training laboratory. Core temperatures of rats were monitored via rectal thermal couple. The differences of survival time and core temperature among these three models were measured. Heat stress including heat load and heat rate of EHS, C-HS and R were quantitatively analyzed.2. To observe different doses of propofol for survival time of EHS rats. SD rats were divided into 3 groups according to propofol doses (PPF-EHS-1, lOmg/kg; PPF-EHS-2,20mg/kg; PPF-EHS-3,30mg/kg), and were intraperitoneally injected with propofol one hour before experiment. Rats were located on the numerical control treadmills (speed=20m/min) in the lab (temperature=38℃, humidity=65%), and were took out from treadmills after they had been running for 90 minutes constantly. Comparing with NC and EHS groups, we observe different doses of propofol for survival time of EHS rats.3. To observe the protective mechanism of propofol in liver injury of EHS rats. Rats, which were in NC group, EHS group and HE group (38℃,90min), were intraperitoneally injected with propofol 30mg/kg 1 hour before experiment. Then the blood samples from 6 groups were collected to measure the plasma levels of PT、FDP、aPTT、D-D、Cr、BUN、ALP、CK、AST、ALT、TNF-α, IL-1β, IL-6 and high-mobility group box 1 (HMGB1) levels of liver and plasma. The pathologic changes of liver using light microscope were abserved. Results:1. Compared with CHS rats, heat rate of EHS rats was significantly higher, time to EHS rats was significantly shorter (p<0.05). However, the heat load of EHS rats was significantly lower and the survival time of EHS rats was significantly shorter than CHS (p<0.05). Compared with R rats, core temperature of EHS and CHS rata were both reached 42℃, The difference is statistically significant (p< 0.05).2. The survival time can be prolonged by propfol(p<0.05), but the core temperature can not been decreased (p> 0.05). The survival time of PPF-EHS-3 is the longest (p<0.05).3. Both EHS and HE rats display excessive activation of systemic inflammation (increased levels of cytokines and HMGB1 in plasma), hypercoagulation (increased plasma levels of coagulation indicator), and tissue ischemia/injury (increased levels of blood biochemical indicators and HMGB1 in liver cytoplasm). EHS rats display stronger systemic inflammation, coagulation, and tissue ischemia/injury than HE rats (p<0.05). Propofol has no effect on systemic inflammation, coagulation, and tissue ischemia/injury of NC rats. However, Propofol can significantly decrease the plasma levels of biochemical indicators, coagulation indicators, cytokines, and HMGB1 in plasma and liver cytoplasm of EHS and HE rats (P<0.05), and relieve the pathological lesion of liver. Conclusions:Propofol pretreatment before the onset of intense exercise and heat-stress can prolong the survival time of EHS rats by decreasing hypercoagulation, systemic inflammation, and tissue ischemia/injury. Propofol can decrease HMGB1 levels in plasma and liver cytoplasm, and improve the liver injury. We can provide more time to rescue exertional heat stroke-induced MODS by using propofol. |
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