The Study Of Protective Effects Chicoric Acid On Myocardial Injury In Rats With Sepsis

Objective To investigate the protective effect of chicoric acid on myocardial injury in rats with sepsis,and to evaluate its relationship with SIRT1/NF-?B signaling pathway.Methods 1.Cellular experiment: The rat cardiomyocytes were treated with lipopolysaccharide(LPS)to establish a model of sepsis myocardial injury and the protective effects of different concentrations of chicoric acid pretreatment on cardiomyocytes were observed.Experimental group: control group(Con),model group(LPS),LPS+CA10?mol/l group(CL10),LPS+CA20?mol/l group(CL20),LPS+CA50?mol/l group(CL50).Experimental contents: the cell viability was detected by CCK-8,the ROS release was detected by microplate method,the apoptosis rate was detected by flow cytometry,and the protein expressions of SIRT1?NF-?B?I?B? and Caspase-3 were detected by Western blot.2.Animal experiment: A model of myocardial injury in rats with sepsis was established by intraperitoneal injection of LPS and the protective effects of chicoric acid on myocardial injury,oxidative stress and serum inflammatory cytokines were observed.Experimental group: control group(Con),sepsis myocardial injury model group(LPS),chicoric acid pretreatment+sepsis myocardial injury group(LPS+CA),chicoric acid pretreatment+EX527(LPS+CA+EX527),SIRT1 inhibitor group(LPS+EX527).Experimental contents: the morphological changes of myocardial tissue was detected by HE staining,the protein expression of SIRT1 in myocardial tissue was detected by IHC,the MDA content and SOD activity in myocardial tissue were detected by chemical colorimetry,the levels of serum TNF-?,IL-6 and CK-MB were detected by ELISA,and the expressions of SIRT1,NF-?B,I?B?,Bcl-2 and Bax were detected by Western blot.Results 1.Cellular experiment showed that compared with Con group,cell viability in LPS group was significantly decreased,ROS release and apoptosis rate were significantly increased,the expressions of SIRT1 and I?B? were significantly decreased,the expressions of NF-?B and Caspase-3 were significantly increased(P<0.05).Compared with LPS group,cell viability was increased in CL10 group,ROS release and apoptosis rate were significantly decreased,the expression of I?B? was increased,and the expressions of NF-?B and Caspase-3 were significantly decreased(P<0.05),but there was no statistically significant difference in SIRT1 expression between LPS group and CL10 group.Compared with LPS group,cell viability was increased in CL20 group,ROS release and apoptosis rate were decreased,the expressions of SIRT1 and I?B? were increased,and the expressions of NF-?B and Caspase-3 were significantly decreased(P<0.05).Compared with LPS group,ROS release in CL50 group was decreased(P<0.05),and there were no significant difference in cell viability,apoptosis rate and SIRT1,NF-?B,I?B? and Caspase-3 expression between LPS group and CL50 group.2.Animal experiment showed that compared with Con group,the cardiomyocytes were severely injuried in LPS group,the levels of serum TNF-?,IL-6 and CK-MB were increased,the SOD activity was decreased and the MDA content was increased,the expressions of SIRT1?I?B? and Bcl-2 were decreased,and the expressions of NF-?B and Bax were significantly increased(P<0.05).Compared with LPS group,the degree of cardiomyocytes injuried was reduced in CA+LPS group,the levels of serum TNF-?,IL-6 and CK-MB were decreased,the SOD activity was increased,and the MDA content was significantly decreased,the expressions of SIRT1,I?B? and Bcl-2 were increased,and the expressions of NF-?B and Bax were significantly decreased(P<0.05).Compared with CA+LPS group,the degree of cardiomyocytes injuried was increased in CA+LPS+EX527 group,the levels of TNF-?,IL-6 and CK-MB in the serum were elevated,the SOD activity was decreased,and the MDA content was elevated,the expressions of SIRT1,I?B?,Bcl-2 were decreased,the expressions of NF-?B?Bax were increased(P<0.05).Compared with CA+LPS group,the degree of cardiomyocytes injuried in the LPS+EX527 group was increased,the levels of serum TNF-?,IL-6 and CK-MB were elevated,the SOD activity was decreased,and the MDA content was elevated,the expression of I?B? was decreased,the expressions of Bax and NF-?B were increased(P<0.05),there were no statistically significant in SIRT1 and Bcl-2 expressions between CA+LPS group and LPS+EX527 group.Conclusion Pretreatment with chicoric acid exerts a protective effect on myocardial injury in rats with sepsis and the protective effects may be related to the activation of SIRT1/NF-?B signaling pathway.