Recombinant HIGF-1 Attenuates Myocardium Aging And Improves Cardiac Function Of Post-Infarction Rats

Part one Recombinant hIGF-1 Attenuates Myocardium Aging and Enhances Myocardium Regeneration of Post-Infarction RatsObjective: IGF-1 belongs to the insulin family of peptides and is known to mediate physiological forms of cardiac hypertrophy.This study used recombinant human insulin like growth factor-1(rhIGF-1) by subcutaneous injection on post-infarction rats and detected whether rhIGF-1 attenuates myocardium senescence and improves myocardium regeneration of post-Infarction rats.Methods: rhIGF-1 were injected into 18 post- infarction rats according to 60 microgram / kilogramme.day-1(ug/kg.d-1) everyday. Another 18 post- infarction rats and 12 sham operation rats were injected with sodium chloride. Blood serum and heart were separately harvested at 1,2 and 4 weeks later. We quantified the mRNA levels of rIGF-1 and TERT in myocardium by quantitative real-time PCR assay. Enzyme-linked immunosorbent assay (ELISA) was used for analysis for the level of hIGF-â… and rIGF-â… protein in serum and myocardium. Expression of P16 INK4a and PCNA protein in myocardiums were separately detected by immunocytochemistry (IHC). Expression of P53 and Pki67 protein in myocardiums were separately detected by Western blotting.Results: Compared with sham group, ELISA analysis disclosed the myocardium level of rIGF-1 protein increased gradually in control and experimental group, especially in experimental group(P<0.01).The serum level of rIGF-1 decreased significantly in post-infraction rats, but these condition was improved in experimental group (P<0.01). The hIGF-1 protein in myocardium were detected in experimental group.Upregulation of the rIGF-1mRNA and TERT mRNA were found in post-infarction rats, especially at 2 weeks after injected rhIGF-1 by RT-PCR (P<0.01).The percent of P16INK4aand PCNA positive cells and the OD value of p53 protein were up to peak at 1 week in control and experimental group (P<0.01).In addition, the percent of P16 INK4a positive cells and the OD value of p53 protein in experimental group were lower than in control group whereas the percent of PCNA positive cells in control group was lower than in experimental group(P< 0.01). The percent of P16 INK4a positive cells in experiment group and the percent of PCNA positive cells in control group were approach the sham group from 2 weeks(p>0.05).The OD of pki67 were increased gradually in control and experimental group, especially in experimental group(P<0.01).Conclusions: rhIGF-1 could improve the expression of rIGF-1mRNA and TERTmRNA in myocardium and promote the serum level of rIGF-1 of post- infarction rats.In addition,It could improve the expression of rIGF-1,PCNA,pki67 protein and suppress the expression of p16INK4a and p53 protein in myocardium of post-infraction rats. rhIGF-1 could provide a new option for the future clinical treatment of heart failure by improving myocardium proliferation and attenuating senescence.Part two Recombinant hIGF-1 Improves Cardiac Function of Post-Infarction RatsObjective:IGF-1 belongs to the insulin family of peptides and is known to mediate physiological forms of cardiac hypertrophy.This study used recombinant human insulin like growth factor-1(rhIGF-1)by subcutaneous injection on post-infarction rats and detected whether rhIGF-1 improve heart function of post-Infarction rats.Methods:rhIGF-1 were injected into 18 post- infarction rats according to 60 microgram / kilogramme.day-1(ug/kg.d-1) everyday. Another 18 post-infarction rats and 12 sham operation rats were injected with sodium chloride. Blood serum and heart were separately harvested at 1,2,4 weeks later.We tested the echocardiogram, hemodynamics,left ventricular mass-to-body weight ratio and the cross section area (CSA) of myocardium.Results:Compared with sham group, ELISA analysis disclosed the myocardium level of rIGF-1 protein increased significantly in control and experimental group, especially in experimental group (P<0.01).The serum level of rIGF-1 decreased significantly in post- infraction rats,but these condition were improved in experimental group(P<0.01).The hIGF-1 protein in myocardium were detected in experimental group.The left ventricular ejection fraction(LVEF), left ventricular fractional shortening(FS), +dp/dtmax of left ventricular and mean arteries pressure (MAP) decreased significantly in control group and experimental group (P<0.01). In addition, control group was lower than experimental group in these parameters (P<0.01). The -dp/dtmax of left ventricular and the left ventricular end-diastole pressure (LVEDP) in experimental group and control group increased significantly (P< 0.01). Although CSA of myocardium in control group and experimental group were increased,only the experimental group had significant different with sham group at 2 weeks (P<0.01). The infarction area in experimental group had no significant different with control group (P>0.05). The left ventricular mass-to-body weight ratio increased significantly in control and experimental group at 1 and 2 weeks, especially in control group (P<0.01).At 4 weeks, the left ventricular mass-to-body weight ratio in experimental group decreased significantly compared with control group.Conclusions:rhIGF-1 could not only enhance myocardium inotropy, but also improve ventricular Remodeling. It could provide a new option for the future clinical treatment of heart failure by enhancing cardiac diastolic contractile function.