Study Of Preventive Effects Of Erythropoietin To Myocard Ac Injury And Expression Of Apoptosis Related Gene In Rats Induced By Isoproterenol

Objective: Cardiovascular disease is fast becoming the number one health concern worldwide.Preservation of myocardium by increasing viable myocarcuum, providing acute and chronic benefits is a major therapeutic objective of drugs. Erythropoietin(EPO) is a hormone known to stimulate hematopoiesis.However,recent research suggests additional properties of EPO,such as proection against ischemic stroke. In our study,we produced myocardiac injury heart model of rats by intraperitoneal injection of isoproterenol(ISO),and detected myocardial enzyme, hemorheology,observed myocardiac necrosis(HE stain),and changes of apoptosis related gene in hearts,and then we used erythropoietin to prevent the heart from injury induced by ISO. Through this stidy we want to approach the mechanism of how can FPO do good to the heart.Methods: .ntraperitoneal injection of ISO produced myocardiac injury model in rats. 70 Sprague-Dawley(SD) rats were randomly divided into 4 groups: (1, ISO group(n=20) :ISO was injected through intraperitoneal way,the dosage was 15mg/Kg; (2)EPO-pre group(n=20):Each rat received recombinant human EPO (5000U/kg,i.p.) at 24 hours before ISO injection; (3) EPO-trea group(n=20): Each rat received recombinant human EPO (5000U/kg,i.p.) at 0.5 hour after ISO injection;(4)placebo group(n=10): Each rat received corresponding injection of saline (i.p.) instead ofISO.At 24 hours after ISO (or saline) injection ,we collected blood samples from abdominal aorta and killed all the rats.We measured the release amounts of creatine kinase(CK),MB isoenzyme of creatine kinase(CK-MB),lacticdehydrogenass(LDH),hydroxybutyric dehydrogenase(HBDH) and aspa tate transaminase(AST),whole blood viscosity,plasma viscosity,red blood cell count(RBC) and hemoglobin(Hb),observed the morphological changes of the heart with HE stain,detected the products of apoptosis related gene caspase-3 and iNOS with SABC immunohistochemical stain.The statistical data was analyzed by analysis of variance,chi-square test.SPSS statistics was used to analyze the data.Results:Placebo group: The release amounts of CK was 629.4 ± 70.1U/L,that of CKMB was 879.3± 66U/L ,that of LDH was 672.4 ± 63.8U/L .that of HBDH was 182.9 + 23.0U/L,that of AST was 103.2 ± 16.7U/L,the low-shearing whole blood viscosity was 12.91 ± 1.28 mpa.s, the moderate-shearing whole blood viscosity was 7.20 ± 0.92 mpa.s, the high-shearing whole blood viscosity was 5.87 ± 0.51 mpa.s, red blooc cell count was 6.83 ± 0.86×10¹²/L,the concentration of hemoglobin was 159.75 ± 13.44,necrotic foci was rare in ventricular myocardium(HE stain),positive index(PI%) of caspase-3 protein was 1.87 + 0.23%, that of iNOS protein was 3.93 + 0.28%.ISO group: Compareing with placebo group,the release amounts of CK was 2136.3 ± 230.7U/L (P<0.01),that of CKMB was 3027.4 + 83.1U/L (P<0.01) .that of LDH was 1922.3± 209.9U/L (P<0.01) ,that of HBDH was 486.9 ± 39.7U/L (P< 0.01),that of AST was 230.0 ±21.9U/L (P< 0.01),the low-shearing whole blood viscosity was 18.72 ± 1.33 mpa.s(P < 0.05), the moderate-shearing whole blood viscosity was 10.36±1.50 mpa.s (P<0.05), the high-shearing whole blood viscosity was 8.93 ± 0.67 mpa.s(P<0.05), red blood cell count was 6.32 ± 0.75×l0¹²/L(P> 0.05),the concentration of hemoglobin was 155.32±17.40g/l(P>0.05),necrotic foci of myocardium was obvious under microscope(HE stain,Rona classification, 1 grade 3 rats, 2 grade 12 rats,3 grade 5 rats,comparing with placebo group, (P<0.01),PI% of caspase-3 protein was 25.67 ± 5.12%, that of iNOS protein was 34.57 ± 3.99%,they rose obviously comparing with placebo group(P<0.01).EPO-pre group: The release amounts of CK was 1174.9± 98.5U/L,that of CKMB was 1396.3 ±143.7U/L,that of LDH was 175.2±174.6U/L ,that of HBDH was 238.1 ± 30.5U/L,that of AST was 167.2 ±33.1U/L,all data were better than ISO group(P< 0.01). Compareing with ISO group ,the low-shearing whole blood viscosity was < .60 ± 1.72 mpa.s(P<0.05), the moderate-shearing whole blood viscosity was 8.70 ± 1.08 mpa.s (P<0.05), the high-shearing whole blood visc...