| Hemorrhagic shock is a common critical ill in emergency medicine,and severe blood loss and shock could cause a cascade of detrimental signaling events which may lead to sepsis and MODS.It is the leading cause of death of patients,and it is a serious threat to the safety of life.Numerous studies have shown that the substrate metabolism in critical ill patients significantly changed in stress state.Metabolic disturbance could lower the patients’ tolerance for traumatic stress,delay the recovery of organism,increase extra burden to organs and Increase mortality.In the traumatic stress state,inappropriate supply of energy and substrate is also considered as a heavy blow to organism.It is proved that abnormal substrates metabolism occur during the period of stress following trauma and shock.The utilization of glucose decrease remarkably which lead to insulin resistance.Lipid mobilization is increased with the increase in fatty acid and lipogenesis is retarded.Increased protein breakdown results in net nitrogen balance.Most of the free fatty acid released from adipose tissue occurs re-esterification in hepatic cells so called "TG-FFA" cycle."TG-FFA" cycle accelerates in traumatic stress.It also could result in ectopic deposition of lipids in visceral organ.Only a little of free fatty acid is used for oxidation which is not enough to meet the demand of energy in the case of stress.In addition,it showed mitochondrial dysfunction in hepatic cells and muscle cells in thermal injury which leaded to decreased fat oxidation.Researchers are claiming that n-3 PUFAs rich in fish oil have regulate effect on lipid metabolism.The main effects of n-3 PUFAs are to promote lipolysis and fatty acid oxidation and to inhibit lipogenesis.Thus,our hypothesis is that lipid metabolism would change and fat oxidation decrease after hemorrhagic shock-resuscitation injury.Fish oil improves fat oxidation which would be beneficial to metabolism intervention and recovery.In this study,we established a stable and repeatable mice controlled hemorrhagic shock-resuscitation survival model by optimzing pre-existing models.It is the solid foundation for follow-up study.A comparison of control group and hemorrhagic shock-resuscitation groups indicated that hemorrhagic shock-resuscitation injury could increase energy expenditure in mice but declined fat oxidation.Be treated with fish oil 5days after hemorrhagic shock-resuscitation could reverse it.It is similar in energy expenditure and fat oxidation between the sham group and fish oil group.It is the possible mechanism that fish oil regulate lipid metabolism by activating PPARs.Activated PPARs up-regulate the gene expression of downstream lipid oxidation related enzyme.This may provide reliable theoretical basis for be fish oil treatment in post-traumatic patient who have lipid metabolic disturbance.It may guide to provide nutrition metabolic support for patients more reasonably and effectively,so as to optimize the treatment.PART ⅠEstablished mice controlled hemorrhagic shock-resuscitation survival model and optimized surgical skills in operationObjective:Established a stable and repeatable mice controlled hemorrhagic shock-resuscitation survival model by optimizing pre-existing models.Method:C57BL/6 mice were used for controlled hemorrhagic shock-resuscitation survival model.The left femoral artery was cannulated with a catheter and the mouse’s blood is withdrawn achieving a mean arterial pressure of 30 ± 5mm Hg.The animal remained in hemorrhagic shock for 1.5hours.After the shock time elapses,the animal is resuscitated.The volume of withdrawn blood was recorded.The mouse’s live time,capacity of activity and weight change were collected.Results:In the 45 cases receiving operation,the successful rate of 36 cases undergoing hemorrhagic shock-resuscitation operation after the model stabilized was 83.3%.80.0%of mice after operation lived no less than 5days.Conclusion:Skillfully microsurgical procedures were important to avoid from hemorrhage during operation,increase achievement ratio,made a recovery in lower extremity activity and prolong the survival time.This model has a long lifetime and is repeatable,which is suitable for follow-up study.PART ⅡThe influence of hemorrhagic shock-resuscitation injury on mice lipid metabolismObjective:Aim to study the influence of hemorrhagic shock-resuscitation injury on mice lipid metabolism.Method:On the basis of mice controlled hemorrhagic shock-resuscitation survival model,48 C57BL/6 mice were assigned to 6groups.One was sham group without any surgery.According to the different time that the mice were sacrificed,the other 5groups were defined as Dayl group(D1 group),Day2 group(D2 group),Day3 group(D3 group),Day4 group(D4 group)and Day5 group(D5 group).The body weight,wet liver weight and epididymal white adipose tissue were collected.Biopsy specimens of liver,epididymal WAT and intestine tissue were taken for histological observation.Liver and WAT tissue were collected for the protein and gene expression related to lipid metabolism.In addition,another 32 C57BL/6 mice applied for assessing the energy metabolism after hemorrhagic shock-resuscitation by CLAMS were divided to 4groups as followed:Sham group,D3 group,D4 group,D5 group.According to the different time after injury that the mice were assessed,the other 3groups were defined as Day3 group(D3 group),Day4 group(D4 group)and Day5 group(D5 group).Obtain the volume of oxygen consumption,the volume of carbon dioxide emission,energy expenditure and RQ of all groups of the corresponding time points.Results:There was remarkable weight loss in mice after hemorrhagic shock-resuscitation injury,especially in D3 group.The epididymal WAT/BW significantly decreased in injury groups.Compare to sham group,D5 group had more oxygen consumption,more carbon dioxide emission and increase in energy expenditure.After hemorrhagic shock-resuscitation injury,the protein and gene expression of CPT-1A,FATP and PPAR-a in liver tissue decreased.The protein and gene expression of FAS and PPAR-γ in adipose tissue also decreased significantly.Conclusion:hemorrhagic shock-resuscitation injury could result in lipid mobilization,increase in energy expenditure but decrease in fat β-oxidation.PART IIIThe effect of fish oil on lipid metabolic intervention after hemorrhagic shock-resuscitation injuryObjective:Aim to study the effect of fish oil on lipid metabolic intervention after hemorrhagic shock-resuscitation injuryMethods:16 C57BL/6 mice were assigned to 2groups:Saline group and FO group,which was treated with saline or fish oil 5days after injury by vena caudal respectively.The body weight,wet liver weight and epididymal white adipose tissue were collected.Biopsy specimens of liver,epididymal WAT and intestine tissue were taken for histological observation.Liver and WAT tissue were collected for the protein and gene expression related to lipid metabolism.In addition,another 16 C57BL/6 mice applied for assessing the energy metabolism by CLAMS were divided to 2groups as followed:Saline group and FO group.They were treated with saline or fish oil 5days after injury by vena caudal respectively.Obtain the volume of oxygen consumption,the volume of carbon dioxide emission,energy expenditure and RQ of these two groups.Results:compare to the sham group in part1,there was remarkable weight loss in Saline group and FO group.The epididymal WAT/BW significantly decreased in these two groups.Compare to Saline group,FO group had lower oxygen consumption,decrease in energy expenditure.After treated with fish oil,the protein and gene expression of CPT-1A,FATP and PPAR-a in liver tissue increased but those of FAS declined.There was no difference in the protein and gene expression of PPAR-y in adipose tissue between these two groups.Conclusion:Fish oil could improve fat β-oxidation after hemorrhagic shock-resuscitation injury and decrease energy expenditure. |
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