| BackgroudOur studies in the past several years indicated that insulin can activate thePI3k-Akt-eNOS signaling pathway, increase endothelial cells secrete NO, decrease theTNF-α level and reduces myocardial ischemic damage. Can insulin further adjustinflammation after myocardial infarction? Whether the anti-inflammation effect of insulincontributes to delaying ventricular remodeling and improving heart function? Our researchwill further observe the effect of insulin in myocardial infarction, investigate therelationship between the anti-inflammation effect and the cardiovascular protective effectof insulin.Aims1. To observe whether insulin inhibit the TNF-α production and alleviate inflammationresponse after in inflammation after myocardial infarction.2. To investigate whether the anti-inflammation effect afforded by insulin contribute todelaying ventricular remodeling and improving heart function.Methods1. Male adult Sprague-Dawley Rats were anesthetized and the LAD was ligated to make the myocardial infarction model. All the rats were randomized to receive the following oneof the five difference treatments,(1) Sham;(2) Saline;(3) Insulin treatment: intravenousinjection of insulin(50U/L,1ml/kg h)15min after ischemic for2h, and hypodermicinjection of insulin (0.5U/ml,1ml/kg/d) for7days;(4) Etanercept treatment:(5)Etanercept combined with insulin treatment: hypodermic injection of etanercept(1mg/ml,1ml/kg) two days before and at the first, forth, seventh day after ischemic operation, at thesame time, intravenous injection of insulin(50U/L,1ml/kg h)15min after ischemic for2h,and hypodermic injection of insulin (0.5U/ml,1ml/kg/d) for7days after ischemicoperation.2. All the rats received echocardiogram testing1d before and1week and4week afterischemic operation, LVESD, LVEDD, EF and FS were measured. After theechocardiogram testing, all the rats will receive hemodynamic examination, MABP, LVDP,and±LVdp/dtmaxwill be measured.3. After hemodynamic examination, all the rats’ heart were taken out quickly and thehearts weight were measured (HW) to calculate HW/BW. And then the hearts were stainedwith TTC-Evans blue to measure infarction sizes.4. Blood was centrifuged at low speed and serum was saved. Myocardial protein wasquantified with BSA. Serum and myocardial TNF-α were detected by ELISAkits.Result1. Compared with the sham group, TNF-α level was increased in the control group bothat the first and fourth week after myocardial infarction. At the same time, insulin treatmentsignificantly decreased myocardial TNF-α level. There were no difference in TNF-α levelamong insulin, etanercept, and the combination of insulin and etanercept.2. At the first and fourth week after MI, compared with sham group, both the LVESDand LVEDD of the control group were increased, while EF and FS decreased in thecontrol group. Compare with etanercept group, insulin treatment decreased LVESD andincreased EF and FS at four week after MI.3. Compare with sham group, LVDP and±LVdp/dtmaxwere decreased in the controlgroup at the first and fourth week after MI. Compare with control group, insulin treatment increased the LVDP and±LVdp/dtmaxat the first and fourth week after MI. Compared withetanercept treatment, both insulin and insulin combinative with etanercept treatmentincreased LVDP and±LVdp/dtmax.4.4weeks after MI, compared with sham group, HW/BW increased both in the controland insulin groups, there were no difference between control and insulin treatment.Compared with etanercept treatment, insulin treatment decreased the infarction size.Conclusion1. Insulin treatment inhibited the TNF-α level at the first and fourth week after MI.Insulin combinative with etanercept treatment didn’t enhance the anti-TNF-α effect ofinsulin.2. Insulin treatment decreased infarction size, delayed ventricular remodeling, andimproved heart function after MI.3. The cardiovascular protection effect of insulin independence to insulin itself inhibitedTNF-α level at myocardium. |
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