Effects Of ω-3 Polyunsaturated Fatty Acids On Inflammatory Immunity And Clinical Efficacy In Sepsis

Introduction Sepsis is the overwhelming and life-threatening response of the human body to infection,which can lead to tissue damage,organ failure and death.Globally,it is estimated that 31.5 million sepsis cases and 19.4 million severe sepsis cases are reported annually,and 5.3 million people may die.The prevalence of sepsis in children is increasing year by year,which is similar to that of adults.The multicenter survey found that the average prevalence of sepsis in children in PICU ward is 8.2%,and the mortality rate is between 5% and 40%.About 25% of the deaths in PICU are related to severe infection,with a mortality rate of 17%.Despite the continuous improvement of the understanding of the pathogenesis,prognosis mechanism,clinical symptoms and signs of sepsis and the progress of various treatment and support technologies in recent years,the exacerbation mechanism of sepsis is still unclear,the specific and effective treatment methods are limited,the process of disease aggravation and even death can not be controlled,and the mortality rate is still as high as 30%-70%.Inflammatory response and immune dysfunction are the main pathophysiological processes of sepsis,which are directly related to the occurrence and development of sepsis.The key to the occurrence and development of sepsis is the interaction of pro-inflammatory factors and anti-inflammatory factors.The release of pro-inflammatory factors triggers inflammation storm.The release of anti-inflammatory factors and lymphocyte apoptosis cause immune system fatigue and immune suppression or incompetence.ω-3 polyunsaturated fatty acids(ω-3PUFAs),including eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA),mainly exist in marine organisms(including fish oil)products.In addition to providing energy and nutrients for the body,they also have the functions of anti-thrombosis,regulating immunity,regulating lipid metabolism,regulating gene expression and so on.They can be used in sepsis diseases and may play a role in inhibiting inflammation and regulating gene expression.The function of immunity and improving cellular immunity is helpful to control infection and improve prognosis.At present,the therapeutic effect of ω-3PUFAs in sepsis has attracted more and more attention.However,the therapeutic effect is inconsistent.There are still many problems,such as timing,dose-effect relationship and clinical course of treatment.Further research is expected.Part Ⅰ: Effects of ω-3 polyunsaturated fatty acids on lymphocyte apoptosis and inflammatory factors in sepsis ratsObjective To investigate the effects of ω-3PUFAs on serum inflammatory factors and apoptosis of thymus and spleen lymphocytes in sepsis rats.Methods Eighty female Sprague-Dawley rats aged 7-8 weeks were randomly divided into low dose treatment group with 0.1g/kg·d ω-3PUFAs,medium dose treatment group with 0.2g/kg·d ω-3PUFAs,high dose treatment group with 0.3g/kg·dω-3PUFAs,control group with 0.1g/kg·d fat emulsion and model group without any fat.The sepsis rat model was established by cecal ligation and perforation.After the establishment of the model,each treatment group was given fat emulsion and different doses of ω-3PUFAs with glucose diluents by tail vein injection.The model group was given the same dosage of glucose injection by tail vein injection.The rats in each treatment group were randomly divided into two subgroups,24 h and 72 h,with 8 rats in each group.The pathological changes of thymus and spleen were observed by hematoxylin-eosin staining,the apoptotic rate of spleen and thymus lymphocyte was detected by TUNEL,and the level of serum inflammatory factors was detected by ELISA.Results The rats with cecal ligation and perforation showed mental fatigue,decreased activity,shivering and crouching,abdominal distention,increased secretion of corners of eyes,erect hair and hypothermia.After execution,the rats were found to have jejunal tube bloating,more hemorrhagic effusion in the abdominal cavity,swelling and necrosis,blackening and adhesion in the cecum.The structure of thymic lobules was intact and the structure of cortex and medulla was clear in different doses of ω-3PUFAs group.The boundary between cortex and medulla in model group and control group was unclear,and lymphocyte was significantly reduced.The structure of red and white pulp in spleen of ω-3PUFAs group could be maintained,and splenic nodules could be seen.The structure of red and white pulps in model group and traditional fat emulsion group was disordered,and splenic nodules were significantly reduced or disappeared Loss.The levels of 24 h IL-6,IL-8,72 h TNF-a and IL-6 in treatment group with different dose of ω-3PUFAs were significantly lower than those in model group and traditional fat emulsion treatment group(P < 0.01);the levels of serum inflammatory mediators TNF-a,IL-6 and IL-8 in medium dose treatment group were significantly lower than those in model group and traditional fat emulsion treatment group(P < 0.01);and the levels of serum inflammatory mediators TNF-a,IL-6,IL-8 and IL-10 in the high dose treatment group were significantly lower than those in the model group and control group(P < 0.01).The levels of TNF-a and IL-6in the high-dose treatment group were significantly lower than those in the low-dose treatment group at 24 h,72h(P < 0.01).The levels of IL-8 in the medium dose group,and high dose group at 24 h were significantly lower than those in the low dose group and medium dose group(P < 0.01).The apoptotic rate of thymus and spleen lymphocyte in different doses of ω-3PUFAs group at 24 h and 72 h was significantly lower than that in model group and control group(P < 0.01),and the apoptotic rate of spleen lymphocyte in high dosage group with ω-3PUFAs at 24 h and 72 h was significantly lower than that in low dosage group(P < 0.05 or P < 0.01).Conclusions ω-3 PUFAs can alleviate inflammatory factors in serum and apoptosis of thymus and spleen lymphocyte in sepsis rats,and it is dose-dependent.The high dose treatment group with ω-3 PUFAs 0.3g/kg·d has the best effect.Part Ⅱ: Clinical effects of ω-3 polyunsaturated fatty acids in the treatment of sepsis in childrenObjective To observe the effects of ω-3PUFAs on infection,hemodynamics,oxygenation,liver and kidney function,myocardial damage and cardiac function,lactate clearance rate,severity of illness and inflammation in children with sepsis.Methods According to the diagnostic criteria of pediatric sepsis,87 children with sepsis in our department from June 2014 to May 2018 were selected and divided into two groups according to random number method,namely 45 cases in the control group and 42 cases in the treatment group of ω-3PUFAs.On the basis of routine treatment,the control group was treated with Intralipid(20% fat emulsion)5 ml/kg.d within 6 hours of admission,while the treatment group with ω-3 PUFAs was treated with multiple fat emulsions(fish oil,SMOFlipid)5 ml/kg.d on the basis of routine treatment.All treatments were treated for more than 7 consecutive days.Comparisons between the two groups: select the maximum difference between the first 24 hours of admission and the seventh day of treatment for pediatric critical illness score(PCIS)and pediatric risk of mortality III(PRISM)score;determine the lactate level of children at 0 and 6 hours with treatment,and calculate the early lactate clearance rate;detect the infection indicators WBC,CRP,PCT,hemodynamics and oxygenation indicators MAP,Pa O2/Fi O2 before and after 7 days of treatment;T,TBIL,ALB,Cr;myocardial damage and cardiac function indicators CK-MB,Tn I,BNP;the serum levels of inflammatory factors including TNF-alpha,IL-1beta,IL-6 and IL-10 in children with sepsis were measured at 0h,72 h and 7d after treatment.Results There was no significant difference in gender,age,weight,disease type,lactate level,the PCIS and PRISM III score between the two groups at admission(P >0.05);there was no significant difference in blood routine,hemodynamics,oxygenation,liver and kidney function,myocardial damage and cardiac function between the two groups before treatment(P > 0.5).After treatment,lactic acid at 6hours was significantly lower in the ω-3PUFAs group than that in the control group(P < 0.05),and lactic acid clearance rate was significantly higher than that in the control group(P < 0.01).At 7th days,the infection status of WBC,CRP and PCT in the ω-3PUFAs group was alleviated,but the levels of WBC,CRP and PCT in the treatment group were significantly lower than those in the control group(P < 0.01);there was no significant difference in hemodynamics,oxygenation index,liver and kidney function,myocardial damage and cardiac function between the two groups(P > 0.05);the PRISM III score decreased and the PCIS increased in both groups,but the PCIS in ω-3PUFAs group was significantly higher than that in control group(P <0.01).There were no significant differences in TNF-a,IL-1β,IL-6 and IL-10 levels between the two groups before treatment(P > 0.05).The levels of TNF-a inω-3PUFAs group were lower than those in control group at 72-hour(P < 0.05),while the levels of TNF-a,IL-6 and IL-10 were significantly lower in ω-3PUFAs group than those in the control group at 7-day(P < 0.01 or P < 0.05).Conclusions ω-3PUFAs has a certain clinical effect in the adjuvant treatment of sepsis in children,which may be related to the alleviation of inflammatory reaction in the process of sepsis.