Study of TNF-α inhibitor on myocardial reperfusion injury by activating Notch1 signaling pathway
WANG Wei-fang
LIU Xiao
JI Xiao-ling
YANG Bo
Abstract：Objective To investigate the protective effect of tumor necrosis factor-α (TNF-α) inhibitor (etanercept) through the transmembrane receptor signaling pathway on traumatic myocardial injury in mice.Methods 36 male mice(10-12 weeks of age) were randomly divided into sham operation group(intraperitoneal injection of 5 ml/kg normal saline), control group (post - traumatic myocardial ischemia - reperfusion injury were prepared, intraperitoneal injection of 5 ml/kg normal saline) and etanercept group (post - traumatic myocardial ischemia -reperfusion injury were prepared, intraperitoneal injection Etanercept 8 mg/kg). TNF-αlevel at 30 minutes after reperfusion and serum cardiac troponin I (cTnI) concentration at 3 hours after reperfusion were measured by enzyme-linked immunosorbent assay (ELISA). The left ventricular ejection fraction (LVEF) was measured 24 hours after reperfusion. TUNEL staining was used to measure the apoptotic rate of cardiomyocytes. The area of myocardial infarction was determined by TTC double staining. The expression levels of intracellular domain of Notch1 (Notch1-ICD) and caspase-3 were measured by western blot.Results The levels of serum TNF-α and serum cTnI, and caspase-3, apoptotic rate of cardiomyocytes and the area of myocardial infarction in the control group and etanercept group were significantly higher than those in the sham operation group (P<0.05). The levels of serum TNF-α and serum cTnI, the expression level of caspase-3, apoptotic rate of cardiomyocytes and the area of myocardial infarction in the etanercept group were significantly lower than those in the control group (P<0.05). The value of LVEF and the expression level of Notch1-ICD were significantly higher than those in the control group (P<0.05).Conclusion TNF-αinhibitors have protective effects on myocardium after myocardial ischemia-reperfusion injury, and its mechanism is related to activation of Notch1 signaling pathway to regulate the expression of caspase-3 protein.
Keywords：Tumor necrosis factor-α inhibitorNotch1 signaling pathwayTraumaReperfusion
Publication Date：2016-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 1504-1507 )