The Study On The Correlation Between Apelin And PCT,hs-CRP And The Changes Of Cardiac Function In Sepsis

Part 1 The Study on the Correlation between Apelin and PCT,hs-CRP and the Changes of Cardiac Function in Sepsis Patients? Background ? Sepsis is a life-threatening multiple organ dysfunction syndrome induced by uncontrolled systematic inflammatory response to infection,characterized by high morbidity,high mortality and high cost.To identify rapidly and take timely appropriate treatment,is crucial to sepsis.But there is still without accurate clinical verification,real-time prediction of indicators and systems to sepsis.For now,the PCT and hs-CRP have been used mostly in sepsis' s diagnosising and monitoring to judge the extent of inflammatory reaction and bacterial infection.Apelin,a peptide hormone and an endogenous ligand of the Apelin receptor,has a certain protective effect on myocardial injury and heart failure in sepsis,which can improve the prognosis.But its relationship with inflammatory factors in sepsis is reported rarely.So,it is necessary to study that Apelin can or not to predict the severity of sepsis and septic myocardial injury.? Objectives ? To study the value of Apelin in early diagnosis of sepsis,prediction of SICM and prognosis of sepsis.?Methods? A prospective study was conducted in 62 patients with sepsis and36 healthy volunteers to detect plasma Apelin,PCT,hs-CRP,IL-1?,IL-6,TNF-?,NT-pro BNP,Echocardiographic indexs at the moment of diagnosis and at the 2nd,3rd and 7th day after enrolled.The APACHE II,SOFA and Murray score of both groups were recorded and take SOFA ? 2 scores as the diagnostic criteria for sepsis.The ejection fraction(EF)? 50%,or the decrease of EF by 10% over the basic level,was used as the criterion for Sepsis-induced Cardiomyopathy(SICM).The relationship between plasma Apelin and PCT,hs-CRP in septic patients was studied by Spearman linear correlation analysis.The efficiency of Apelin to diagnosis SICM was evaluated with the receiver operating characteristic curve(ROC).Multivariate linear regression analysis was performed on APACHE II,SOFA and Murray as dependent each points,respectively,independent variables as Apelin and so on to investigated the prognostic significance of Apelin in sepsis.?Results? Apelin increased significantly in the early stage of sepsis,and was related to the severity of sepsis.The significant correlation between Apelin and PCT was at 3rd and 7th day after enrolled(r = 0.399,P = 0.001;r = 0.423,P = 0.001,respectively),no correlation between Apelin and hs-CRP.In SICM cases,the area under the Apelin curve at each points was statistically significant(P ? 0.05).Multiple linear regression analysis showed that there was a linear relationship between Apelin and APACHE II at each points,as well between SOFA at the moment of diagnosis and the 2nd,7th day after enrolled,the relationship between Murray and Apelin was linear only at the 3rd day(P = 0.007).? Conclusions? The expression of Apelin is significantly increased in sepsis,which is of significance for early warning of sepsis,especially to identify myocardial injury in sepsis,and judging the severity and prognosis of sepsis.Part 2 Apelin protects against sepsis-induced cardiomyopathy by inhibiting the TLR4 and NLRP3 signaling pathways?Background? Sepsis-induced Cardiomyopathy(SICM)is caused by a variety of mechanisms,in which the innate immune and inflammatory responses are closely related to the occurrence and development of SICM.The activation of TLR4 signaling pathway and NLRP3 inflammasome can promote the expression of NF-?B.Thus,controlling the expression of pro-inflammatory cytokines,which is considered to play an important role in regulating cardiac dysfunction.Our previous clinical data showed that the level of Apelin was significantly increased in patients with SICM.Therefore,we hypothesized that there was a relationship between Apelin and TLR4,NLRP3.And the increase of Apelin had myocardial protection in SICM or not.This study was conducted to verify the hypothesis.?Objectives? To investigate the protective mechanism of Apelin in myocardial injury model of sepsis rats.? Methods ? 30 Sprague Dawley rats were randomly divided into 3 groups:cecal ligation and puncture(CLP)sepsis model group,Apelin administrated for consecutive 3 days after CLP in the treatment group and sham operation control group.The rats' behavior and mortality were observed daily after the operation.All rats were putted to death in 7 days after the operation,and the blood samples and heart specimens were collected.ELISA was used to detect plasma IL-1?,IL-6and TNF-? in each group.H&E and TUNEL staining were used to observe the morphology and apoptosis of cardiomyocytes in rats.Western blot was used to detect TLR4 signal pathway related proteins and NLRP3 inflammasome proteins after cardiac homogenate,and the related proteins were quantitatively detected byBCA method.?Results? The mortality rate of sepsis rats decreased after Apelin intervention(P = 0.021),the damage of cardiac myocytes was significantly reduced and apoptosis decreased;TNF-?,IL-1? and IL-6 in CLP + Apelin group was significantly lower than CLP group(P < 0.05);the expression of TLR4,P-I?B?and p-P65 in CLP + Apelin group was significantly lower than CLP group(P <0.001);the expression of NLRP3,ASC and Caspase-1 in CLP + Apelin group was significantly lower than CLP group(P < 0.001).?Conclusions? Apelin antagonizes cardiac impairment in sepsis by attenuating TLR4 and NLRP3 signaling-mediated inflammatory responses,and might therefore be a therapeutic target for sepsis cardiomyopathy.