| Hepatic Ischemia Reperfusion (HIRI) is a pathological and physiological process which is common in the hospital. It often appears as a consequence of hemorrhagic shock, liver transplantation, congestive heart failure, trauma and respiratory failure, causes damage to remote organ as well. However, its mechanism has been still unclear until now, the main viewpoint involves damage-associated molecular pattern (DAMP), reactive oxygen species(ROS),mitochondrial dysfunction, neutrophil activation and so on. Modulation of HIRI can be achieved in various ways, including ischemic preconditioning, hypothermia, pharmacological agents to decrease HIRI, but it is still far away from solution. Hydrocinnamoyl-L-valyl pyrrolidine (AS-1)is one kind of mimic of myeloid differentiation primary response gene88,Myd88,which is a very important signal molecular taking part in HIRI process, it is small molecular weight and has been proved the benefits in process of myocardial ischemia-reperfusion injury,but whether there is any possibility of its protection on liver in HIRI is rarely reported.In this study, using a rat model of HIRI, we investigated the impact of AS-1postconditioning on hepatic ischemia reperfusion injury in rats on liver function, inflammatory factors, and neutrophil, discussed whether there is any protection of AS-1on HIRI and how the mechanism works.Objective:(1)To study the establishment of the model of injury on liver triggered by ischemia and reperfusion after traumatic hemorrhagic shock and resuscitation, in order to provide a reliable model for the study of HIRI.(2)Patients with trauma and hemorrhagic shock always have liver injury,IL-1βis one of the important inflammatory factors taking part in this processes. We observed changes of the items which related to liver injury based on the model of trauma and hemorrhagic shock of rats, to investigate the effects of AS-1(hydrocinnamoyl-L-valyl pyrrolidine), which mimic the structure of TIR(Toll IL-1receptor homology)/BB loop of Myd88,an important molecule of IL-1βsignal pathway, on the injury of liver triggered by ischemia and reperfusion after traumatic hemorrhagic shock and resuscitation in rats.Methods:(1) All the rats were performed by modified Wigger’s and made femoral fractures to establish an animal model of trauma and hemorrhagic shock.60SD rats were randomly divided into2groups, group Sham and group THS, each of them divided into another5groups, specimens were taken at0h,3h,6h,12,24h after the whole process, each group contains6rats, and all were anesthetized, intubated Carotid, femoral vein, femoral artery. The rats in group THS, their left femu were clamped to fracture and all bled from right femoral artery to a mean arterial pressure(MAP)of30mmHg, kept it between30and40mmHg for1hour, then resuscitated them with blood and lactated Ringer’s solution in proportion at a uniform speed in30min to complete the model. Then we observed morphology of liver and intestine, the pathological manifestations, monitored the activity of ALT of each group.(2)32healthy male SD rats were randomly divided into4groups:group A, group trauma hemorrhagic shock and resuscitation(THSR);group B,group THS+AS-1;group C, group THS+dissolution medium; group D,control group. All of them were anesthetized, intubated Carotid, femoral vein, femoral artery. The rats in group A,B,C,their left femu were clamped to fracture and all bled from femoral artery to mean arterial pressure(MAP)of30mmHg,and kept it between30and40mmHg for1hour,then resuscitated them with blood and lactated Ringer’s solution in proportion at a uniform speed in30min. The rats in group B were given AS-1(160mg/kg) just before resuscitation, group C were given dissolution medium instead. Group D were not treated.3hours after resuscitation for group A,B,C,kept the instrument for2.5hours and waited another3hours for group D, we detected serum of all rats to see the activity of ALT,AST and the level of IL-1(3,TNF-a,left livers were removed to detect the activity of MPO, the pathological changes of livers were evaluated on light microscopy.Results:(1)Compared with group Sham, the activity of ALT in group THS at3h,6h,12h,24h after the whole process increased obviously,(204.09±27.41VS92.29±8.84,233.89±36.07VS109.02±17.03,222.65±41.82VS90.47±9.98,197.18±41.82VS75.24±9.98),P<0.05,differences were statistical significance. And3h after the whole process, there are obvious difference in the morphology of liver and intestine and the pathological manifestations between group THS and group Sham.(2)Compared with group D.the activity of ALT(206.13±23.67,110.45±18.20,210.73±28.43VS87.55±6.8),AST(621.00±40.61,409.13±63.53,600.25±44.05VS327.03±36.23),the level of IL-1β(621.00±40.61,409.13±63.53,600.25±44.05VS327.03±36.23),TNF-a(214.13±21.24,145.25±12.42,206.50±36.97VS93.51±9.86),an-d the activity of MPO(1.72±0.12,1.20±0.11,1.67±0.14VS0.90±0.21)increased in group A,B,C(all P<0.05).Compared with group A and C, group B was lower on the items we mentioned above (all P<0.05),there is no obvious difference between group A and group C(P>0.05).Conclusion:(1) The rats trauma hemorrhagic shock with hepatic ischemia reperfusion which were performed by us is reliable to study the basic and clinical problems of HIRI because of high success rate and model stability.(2)TIR/BB-loop mimetic AS-1can attenuate liver ischemia/reperfusion injury after traumatic hemorrhagic shock and resuscitation in rats by decreasing the level of IL-1β,TNF-ain serum and the deposition of the neutrophils in livers. |
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