| Objective: The research adopt the method of cecum ligation rat sepsis was observed inanimal model of sepsis rat myocardial damage situation, discusses the application of(Recombinant Human Tumor Necrosis Factor－α ReceptorⅡ：IgG Fc Fusion Proteinfor Injection rhTNFR: Fc) early intervention to sepsis myocardial damage of protection,and preliminary study the mechanism of action.Methods:108grade clean SD rats, all female, were randomly divided into3groups:(1)sham operation group (group A, n=36), sepsis group (group B, n=36), sepsis addrhTNFR: Fc group (group C, n=36);(2) Group A animals were got blood sample fromabdominal aorta after weighing and anesthesia, then took cecal exploration operation，got the blood sample at the time point of3h,9h,,24h,36h,48h and72h respectively,using enzyme-linked immunoassay detection the level of tumor necrosis factor (TNF-α), interleukin1(IL1) and cardiac troponin I (cTnI), to keep heart tissue and usingWestern blot experiments (Western blot method) for the nf-kappa B P65proteindetection. Each phase point had6rats.(3)Group B animals were carried out the samesteps with the sham operation group after weighing,anesthesia and cecum ligationperforation technique, using enzyme-linked immunoassay detection the level of tumornecrosis factor (TNF-α), interleukin1(IL1) and cardiac troponin I (cTnI),got theblood sample at the time point of3h,9h,24h,36h,48h and72h respectively, then tookthe heart tissue and used Western blot experiments (Western blot method) for thenf-kappa B P65protein detection. Each phase point had6rats.(4) Group C animalswere taken cecum ligation perforation (CLP), postoperative immediately from externalcarotid venous injection of etanercept (rhTNFR: Fc) aqueous solution2ml/kg (1g/L).Group C animals were carried out the same steps with the sham operation group and gotthe blood sample at the time point of3h,9h,24h,36h,48h and72h respectively, using enzyme-linked immunoassay detection the level of tumor necrosis factor (TNF-α),interleukin1(IL1) and cardiac troponin I (cTnI),and then took the heart tissue and usedWestern blot experiments (Western blot method) for the nf-kappa B P65proteindetection. Each phase point had6rats.(5) All of the data with the form "mean±standard deviation" were said by SPSS13.0statistical software package for analysis,and correlation analysis by Spearman rank correlation analysis.Result:1. Variation of serum TNF-αSepsis add rhTNFR: Fc group and sepsis group in CLP postoperative serum levelsof TNF-α increased compared with sham operation group(p <0.05), and Sepsis addrhTNFR: Fc groups increased to the highest values at3h point (257.619±5.558pg/ml),then they have a downward trend in both groups (p <0.05), from3h to72h sepsis andrhTNFR: Fc group were significantly lower than the sepsis group(p <0.05).2. Variation of serum IL–1Sepsis add rhTNFR: Fc group and sepsis group in CLP postoperative serum levelsof IL–1increased compared with sham operation group (p <0.05), and Sepsis addrhTNFR: Fc groups increased to the highest values at3h point (179.23±2.506pg/ml),then they have a downward trend in both groups (p <0.05), from3h to72h sepsis andrhTNFR: Fc group were significantly lower than the sepsis group (p <0.05).3. Variation of serum c T nISepsis add rhTNFR: Fc group and sepsis group in CLP postoperative serum levelsof c TnI increased compared with sham operation group(p <0.05), and Sepsis addrhTNFR: Fc groups increased to the highest values at3h point(228.332±3.635pg/ml),then they have a downward trend in both groups (p <0.05), from3h to72h sepsis andrhTNFR: Fc group were significantly lower than the sepsis group(p <0.05).4.(NF-κB) P65protein expressionSepsis add rhTNFR: Fc group and sepsis group3h after CLP (NF-κB) P65protein levels were higher than sham operation group (p <0.05), then they have a downwardtrend, sepsis add rhTNFR: Fc group decreased faster than the sepsis group, and in24h,36h and48h sepsis add rhTNFR: Fc group (NF-κB) P65protein levels were below thesepsis group, then in72h there were no significant difference between the two groups.5.Correlation analysis among TNF-α, IL-1and cTnITNF alpha and cTnI has significant positive correlation, the correlation coefficientwas0.393, P=0.164; IL-1and cTnI has significant positive correlation, the correlationcoefficient was0.980, P=0.000.Conclusion:1. In the process of acute myocardial by sepsis in rats, serum cTnI early rose, reflectingthe myocardial damaged. Through the detection of serum cTnI levels can reflect theserious degree of acute myocardial injury.2.During occurrence and development of sepsis, serum levels of TNF-αand IL-1insepsis rats rose and had significant positive correlation, indicated excessive expressionof inflammation factors closely related to myocardial injury,(NF-κB) P65proteinexpression enhanced, presumably in sepsis through the nf-kappa B signal transductionpathways induce excessive expression of cytokines and myocardial injury.3.After early application rhTNFR: Fc intervention in sepsis rats, serum levels of cTnIdesent, myocardial injury released,(NF-κB) P65protein expression alleviated,explained rhTNFR：Fc through inhibiting TNF-α mediating the NF-κB signaltransduction pathways,blocked excessive expression of cytokines, regulateduncontrolled inflammatory response, and had a positive effect on myocardial injury. |
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