| Objective:Multiple organ dysfunction syndrome(MODS)refers to a systemic syndrome in which two or more systems or organs become dysfunction or failure.Mortality is high in hospitalized patients with severe MODS.In patients with severe burn MODS,post-traumatic stress hyperglycemia and the different degrees of systemic inflammatory response,islet beta cells get impairment of different degrees,inflammatory cytokines can make islet beta cells apoptosis,result in a decline in insulin secretion and glucose stress too much,which will further promote the development of the inflammatory response,stable blood sugar levels in the appropriate range is very important for the prognosis of MODS.Pyruvate is a scavenger of reactive oxygen species(ROS)and an intermediate product of glycolysis in vivo.It is the core link of the metabolism of the three major nutrients.Sodium pyruvate is the most common pyruvate and plays an increasingly important role in clinical practice.Sodium pyruvate can be intraperitoneally injected to prevent and treat organ dysfunction and/or failure.Direct intraperitoneal resuscitation(IR)with sodium pyruvate increases blood flow to the damaged pancreas by 57%.Oxidative stress and inflammatory cytokines play an important role in inducing islet beta cell dysfunction and development,and the use of antioxidants can significantly improve symptoms.Studies have shown that sodium pyruvate can improve the glucose metabolism of shock cells,enhance the antioxidant and alkalization of the body,and protect tissues and organs in the absence of oxygen or severe hypoxia.Compared with sodium chloride,sodium pyruvate is a better recovery solution.In clinic,the most commonly used 0.9% sodium chloride in anti-shock and major surgery is easy to cause hypercaloric acidosis and aggravate acid-base balance disorder when overused alone.The newly prepared sodium pyruvate solution has the sodium content close to the physiological level,and the osmotic pressure was also very stable.A large number of studies have shown that sodium pyruvate have the protective function of the organs.These studies mainly focused on the protection of sodium pyruvate on the function of myocardial cells,nerve cells,red blood cells and other tissue cells,however there were few reports onthe protection of sodium pyruvate on the pancreatic islet beta cell function of severely scalded MODS mice.In this study,on the basis of successful establishment of severe burns MODS mice model,sodium pyruvate was used as an intervention in the experimental group and normal saline was used in the control group,blood samples were collected at different time points after injury respectively to detect the serum alanine aminotransferase(ALT),creatinine(CREA),creatine kinase MB isoenzyme(CK-MB),interleukin-6(IL-6),superoxide dismutase(SOD),glucose(GLU)and Insulin(Insulin).Depend on HOMA-β formula and pathological morphology to evaluate the function of islet beta cells in mice.To investigate the protective function of sodium pyruvate on pancreatic islet cells,so as to provide experimental reference and new ideas for the prevention and treatment of MODS by improving the function of islet cells to regulate glucose metabolism.Methods:1.140 Kunming mice without special pathogens at the age of 6-8 weeks were selected.Random number method group in which 120 mice,male and female half were made 30% total body surface area(TBSA)Ⅲ severe burns MODS mice model:Fixed limbs in mice,celiac injection of 3.3% chloral hydrate anesthesia(10 ml/kg)back 30% body surface area of shearing under 90 ℃ after burn in an electric constant temperature water tank for 10 seconds,two hours later,intraperitoneal injection of endotoxin(1.0 mg/ml,5.0 ml/kg),saline resistance to shock,divided into the MODS saline control group after 60(1d,3d,5d after injury variety 20 in each group)and the MODS after sodium pyruvate treatment group(60(1d,3d,5d after injury variety 20 in each group),In the pre-injury healthy group,20 mice were not treated with scald.2.MODS normal saline control group: 60 mice were intraperitoneally injected with 1mL 0.9% normal saline,and 1mL 0.9% normal saline was intraperitoneally injected 8 hours after scald.3.MODS sodium pyruvate treatment group: 60 mice were intraperitoneally injected with 2.5% sodium pyruvate solution 1mL,and then intraperitoneally injected with 2.5% sodium pyruvate solution 1mL 8 hours after scald.4.The normal saline control group and the pyruvate treatment group fasted for12 hours at each time point 1d,3d and 5d after the injury,respectively.Before injury,mice in the healthy group were given adaptive feeding for three days and fasted for12 hours.Blood was collected from their hearts.Serum was taken from each group and stored at-80 ℃ in the ultra-low temperature refrigerator.The levels of ALT,CREA,CK-MB,GLU and SOD were measured by a fully automatic biochemical analyzer.IL-6 and Insulin levels were measured by Elisa,and the functional index of HOMA-β cells was calculated by the formula:Functional Index of HOMA-β cells=20×FINS/(FBG-3.5)5.Abdominal pancreas tissues were collected from the normal saline control group,the sodium pyruvate treatment group and the pre-injury healthy group at each time point for HE staining and pathological section analysis after heart blood collection.Results:1.120 30% total body surface area(TBSA)Ⅲ severe burns MODS injury in mice after the deaths of two experimental groups: 60 normal saline control group mice each time point 1d,3d and 5d mortality rates were 35%,45%,50%;The mortality rates of 60 mice treated with sodium pyruvate at 1d,3d and 5d were 25%,30% and 35%,respectively.There was no accidental death in 20 healthy mice before injury,and the difference between the groups was not statistically significant(P>0.05).2.The experimental group made 30% total body surface area(TBSA)Ⅲ after severe burns MODS mice model,both sodium pyruvate in treatment group and normal saline control group there were shudders in mice,decreased activity,depressed,spirit such as poor performance,compared with healthy mice,the experimental mice survival rate dropped significantly,especially in normal saline control group,sodium pyruvate in treatment group than the normal saline control group to reduce the mortality rate of severe burns MODS in mice.3.Compared with the indicators of liver function,kidney function and cardiac function in the sodium pyruvate treatment group and the normal saline control group,the serum ALT,Cr and CK-MB levels of the mice in the sodium pyruvate treatment group on 1d,3d and 5d after injury were lower than those in the normal saline control group at the same time point(P<0.01).4.Compared with the normal saline control group,the level of inflammatory factor IL-6 in the sodium pyruvate treatment group was lower than that in the normal saline control group at the same time point(P<0.01).5.Compared with the two experimental groups,the normal saline control group,the SOD level of 1d in the sodium pyruvate treatment group was not significantly different from that in the normal saline control group at the same time point(P >0.05).The SOD level of 3d and 5d after the injury in the sodium pyruvate treatment group was higher than that in the normal saline control group at the same time point(P<0.01).6.The HOMA-βcell functional index level of the sodium pyruvate treatment group on 1d,3d and 5d after injury was higher than that of the normal saline control group at each time point(P<0.01),which was better than that of the normal saline control group at each time point.7.HE staining results of pancreatic tissues in each group: before injury,the pancreatic islet tissues of healthy mice were arranged in a dense and regular manner,with the same cell size and clear cell boundaries.The pancreatic tissue of mice with severe scald MODS showed different degrees of unclear cell contour and infiltration of inflammatory cells on 1d,3d and 5d in the normal saline control group,which was more serious in the 3d group than in the 1d and 5d groups.The pancreatic tissue morphology in the treatment group with MODS sodium pyruvate was slightly improved compared with that in the control group.Conclusion:Dysfunction of islet beta cells often occurs in MODS after severe burns,and hyperglycemia and inflammatory reactions occur after trauma(scalding)injury.Sodium pyruvate,as an antioxidant and anti-inflammatory agent,may contribute to the protection of pancreatic tissue and improve the function of islet beta cells. |
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