The Mechanism Of Ischemic And Hypoxic Injury Of Liver After Burn And Delayed Resuscitation In Rats At High Altitude

Objective To evaluate liver injury and its mechanism after severe scald with delayed fluid resuscitation in rats at different altitude.Methods A total of 240 male Wistar rats were applyed as objects of this study. They employed as the experimental models (TBSA30%, III degree), and then they were randomly divided into 3 groups at different altitudes (1517m and 3848m):immediate fluid resuscitation group (IFR),delayed fluid resuscitation group (DFR) and sham group (SG). The liver sample were harvested at 1h,6h,12h,24h,72h and 168h after scald respectively. Pathological technique, hand-made tissue microarry, TUNEL, immunohistochemistry and image analysis techniques were used to detect pathological changes of liver, liver cells apoptosis, protein expressions of HIF-la, P53, Bcl-2, HSP70 and their relationship.Results 1. With the altitude increased, liver cells appeared swell, and cytoplasm puffing obviously, and the inflammatory cell infiltration could be seen in portal area and hepatic sinusoid. Apoptosis and cellular necrosis to increase gradually.2. The expression level of HIF-la and p53 were much higher in experimental groups than that in SG, as with the increase of altitude HIF-1a and p53 expression enhanced, and expressed much higher in DFR than those in IFR, the experimental groups in 3848m higher respectively than those in 1517m at 6h,12h,24h and 72h after injured (P <0.05).3. The positive expression of Bcl-2 appeared in cytoplasmic. A weak expression of Bcl-2 was discerned in SG in both altitude, The expression level were much higher in DFR than those in IFR at 6h(P<0.05), the experimental groups in 3848m higher respectively than those in 1517m at 6h and 72h after injured(P<0.05), and reach the peak at 6 h after injury (P<0.01). Its expression markedly decreased at 12 h following injury, and declined the lowest level at 24h.4. The positive expression of HSP70 significantly appeared in cytoplasmic. The expression level of HSP70 were much higher in experimental groups than those in SG, at 3848m altitude than those at 1517m attitude, and in DFR than those in IFR (P<0.05).5. The expression level of TUNEL were much higher in experimental groups than those in SG, as with the increase in altitude TUNEL expression enhanced, and expressed much higher in DFR than those in IFR, the experimental groups in 3848m higher respectively than those in 1517m at 6h,12h,24h,72h time points (P<0.05)Conclusion1. With the altitude increased, there were obviously differences of pathological changes of liver after severe scald with delayed fluid resuscitation.2. The apoptosis of hepatocyte was involved in liver injury after severe scald with delayed resuscitation in rats at high altitude, and the apoptotic rate of hepatocyte increased after severe scald with delayed fluid resuscitation at high altitude.3. HIF-la, P53 may participate in liver injury after severe scald with delayed fluid resuscitation at high altitude.4. P53 and Bcl-2 participated in the injury process, and they played roles in the regulation of apoptosis of hepatocyte.5. HSP70 may Participated in liver injuries caused by severe scald at high altitude area,which reflects the level of body's stress or degree of injury to a certain extent, an d can be used as biological markers of cellular stress response.