Protective Effect Of Curcumin On Myocardial Injury Of Sepsis In Rats And Its Effect On HMGB1

Background: Sepsis is an important public health problem with high mortality rate among worldwide.It can lead to multiple organ dysfunctional syndrome in the end which is a pathological state fatal for humans.Moreover,sepsis induced myocardial injury is a common complication of sepsis.The incidence of sepsis across the world is as high as 40%,and cardiac dysfunction can not only aggravate the condition of sepsis but also affect the prognosis of sepsis.There are many mechanisms involved in septic myocardial dysfunction,such as oxidative stress,bacterial toxin,apoptosis and cytokines,mitochondria damage etc.Curcumin performs many functions such as anti-oxidation,anti-inflammation,anti-apoptosis and free oxygen radical scavenging etc.This is consistent with the underlying mechanism of anti-septic myocardial injury.High mobility group protein(HMGB1)is a highly conserved DNA binding protein among all kinds of eukaryote.HMGB1,whose function varied according to its molecular localization.Meanwhile,HMGB1 is located in the nucleus under physiological conditions.It contains stable nucleosome structure and can promote gene recombination,repair,transcription etc.It is known as another name--DNA chaprone.HMGB1 is deemed as an important cytokine factor during inflammatory,when sepsis occurs,it can be released from nucleus to extracellular.Some studies have testified that curcumin can down-regulate the receptor of HMGB1 thus in turn can significantly reduce the transfer,release and expression of HMGB1 to the cytoplasm.Objective: The purpose of this study was to explore the effect of curcumin on septic myocardial injury and its functional molecular mechanisms on HMGB1 both through in vitro and in vivo experiments,by figuring out the questions mentioned above maybe we can provide a new strategy and insight for the treatment of septic myocardial injury.Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: sepsis group(CLP),sham operation group(Sham),and intervention group(Cur),the 10 rats in each group.CLP group were treated with cecal ligation and perforation to establish sepsis rat model.The Sham group only opened the abdominal cavity and did not ligate the caecum,and the Cur group were treated by intraperitoneal injection of curcumin according to 100mg/kg after modeling.The blood and heart of each group were collected at 6h and 24 h after the surgery.The serum CK and CK-MB level was detected by automatic biochemical analyzer.The pathological changes of myocardium were observed by microscope.The expression of HMGB1 was detected by Elisa and PCR techniques.The data of the experiment was statistically processed using SPSS18.0 software package.The measurement data are expressed as mean ±standard deviation(x ±s).All data are tested for normal distribution.Independent sample T test was used to compare the mean values of two samples,and homogeneity test of variance and one-way ANOVA were performed in multigroup mean comparison,and the difference was statistically significant in non-conforming normal distribution with rank sum test.p<0.05 was considered statistically significant.Results:(1)The general state of the rats in the CLP group was alleviated compared with that in the Cur group.(2)Observation of cardiac pathological light in each group: Compared with Sham group,myocardial fiber rupture,interstitial edema,necrosis of myocardial cells,enlarged intercellular space and congestive capillaries were observed in each group.The above changes of cardiomyocytes in the 24 h group were more serious than those in the 6h group.The above changes of cardiomyocytes in the Cur group were significantly less than those in the CLP group,and the cardiomyopathy score in the 24 h sepsis group was more serious than that in the 6h CLP group(p<0.01),and the difference was statistically significant.The score of cardiomyopathy in 6h and 24 h CLP group was significantly lower than that in Sham group(p<0.01),and the degree of cardiomyopathy injury in curcumin group was less than that in 6h CLP group(p<0.01).The pathological injury degree of curcumin 24 h group was significantly lower than that of sepsis 24 h group(p=0.033).(3)Comparison of CK-MB and CK in each group.Compared with Sham 6h group,CK-MB level in CLP 6h group was significantly higher(p<0.01),while CK-MB level in Cur 6h group was lower than that in CLP 6h group(p<0.01).Compared with the Sham 24 h group,the levels of serum CK-MB in 24 h of CLP group were significantly higher(p=0.001).However,the level of CK-MB in Cur 24 h group was lower than that in CLP 24 h group(p=0.046),the difference was statistically significant.The result of serum CK change was consistent with that of CK-MB.(4)Comparison of serum HMGB1 levels in each group.Compared with Sham 6h group,the plasma HMGB1 level in CLP 6h group was significantly higher(p<0.01).Compared with the CLP 6h group,the plasma HMGB1 level in Cur 6h group was significantly lower(p=0.005),however,the level of plasma HMGB1 level in CLP 24 h group was lower(p=0.079).The level of plasma HMGB1 in 24 h of CLP group was significantly higher than that of Sham 24 h group(p=0.078).The level of plasma HMGB1 in 24 h of Cur group was significantly lower than that in 24 h of CLP group(p=0.033).The difference is statistically significant.(5)Comparison of HMGB1 gene levels in each group.Compared with Sham 6h group,the expression of HMGB1 m RNA in myocardial tissue of CLP 6h group was decreased(p=0.037),and the difference was statistically significant;Compared with the CLP 6h group,the Cur 6h group expression levels increased,the difference was not statistically significant(p=0.438).Compared with the Sham 24 h group,the expression of HMGB1 m RNA in the myocardium of rats with CLP 24 h was increased(p=0.334),and the difference was not statistically significant.Compared with the CLP 24 h group,the expression level of HMGB1 m RNA in Cur 24 h group was decreased(p=0.208),and the difference was not statistically significant.The expression of HMGB1 m RNA in the CLP 24 h group was higher than that in the CLP 6h group(p=0.438),and the difference was not statistically significantConclusions:Curcumin has protective effect on acute myocardial injury in CLP model rats.Curcumin can be used as an effective drug for the treatment of sepsis and myocardial tissue protection,curcumin can reduce the level of extracellular HMGB1,but has no effect on gene level.So,we wonder it may play an anti-inflammatory effect by affecting the release and translocation of HMGB1.