The Effect Of Inflammatory Factors And The Protective Mechanism Of EPO On Hypothermia Heart Failure

Objective:To investigate the effect of inflammatory factors and the protective mechanism of EPO on hypothermia heart failure.Methods:120 male SD rats were randomly divided into two groups.①Control group (group A,n=10),②Adriamycin group (ARD group,n=110).To construct heart failured model,all rats in ARD group were intraperitoneally injected with adriamycin (2.5mg·kg-1·d-1,twice every week,general 5 weeks).76 rats successfully modeled in ARD group were randomly divided into 4 groups.①Homoeothermy heart failure group(group B,n=19),②Hypothermia heart failure group(group C,n=19),③Homoeothermy heart failure group interved by EPO(group D,n=19),④Hypothermia heart failure group interved by EPO(group E,n=19). Both group D and E received intraperitoneal injection with EPO(4000U·kg-1·d-1,continuously 4 days),group A,B and C received intraperitoneal injection with the same volume of 0.9% saline(once a day,continuously 4 days). During the seventh week, rats in group C and E were put into the climate chamber once a day(4℃,4 hours each time, continuously 4 days),while rats in group A,B and D remained in the homoeothermy condition. In the eighth week, all rats heart function was measured by transthoracic echocardiography(TTE).The pathological changes of myocardial tissue were observed by HE sataining, the protein expression of IL-6,IL-1βand TNF-a were observed by immunohistochemistry and the mRNA expression of IL-6,IL-1βand TNF-a were measured by qRT-PCR.Result:During the process of modeling,34 rats died for ADR poisoning,All rats in group A lived normally without poisoning or death. And then,4 rats died in group C and one rat died in group E during the experiment of low temperature.(1)Cardiac function:Compared with group A, LVEDD and LVESD of the other four groups increased (p<0.05), LVEF and FS decreased (p<0.05). Compared with group B, the LVEDD and LVESD of group C and D increased (p<0.05,P<0.01 respectely). LVEF,FS of group C decreased (p<0.05, P<0.01 respectely). Compared with group D, LVEDD and LVESD values of group E increased (p<0.01),LVEF and FS decreased (p<0.01).The results showed hypothermia could lead to further deterioration while EPO could improve cardiac function of heart failure rats.(2) Cardiac histopathological changes:The morphology of cardiac cells of group A was normal.while cardiac cells of the other four groups shows different degree of glassy degeneration or necrosis in myocardial cells, hyperemia and oedema in cardiac stroma.Compared with groupB, the histopathological changes of group C were worse, glassy degeneration or necrosis in myocardial cells and moderate hyperemia,oedema in cardiac stroma were more serious.The histopathological changes of group D were better than in group B.(3)Immunohistochemistry:The cytoplasm of the cardiomyocytes in myocardial tissue was buffy and brown stainned in the light microscope.Compared with group A, the percentage of cells expressed of IL-6,IL-1βand TNF-a protein in myocardial tissue of the other four groups increased significantly (p<0.05). Compared with group B, the percentage of positive cells of group C increased significantly (p<0.05),and the percentage of positive cells of group D increased significantly (p<0.05). Compared with group D, the percentage of positive cells of group E increased significantly (p<0.05)(4) The expression of gene:Compared with group A,the expression of IL-6,IL-1βand TNF-a mRNA in myocardial tissue of the other four groups increased significantly (p<0.01). Compared with group B, the expression of IL-6,IL-1 (3 and TNF-a mRNA of group C increased significantly (p<0.01), and the expression of IL-6,IL-1(3 and TNF-a mRNA of group D increased significantly(p<0.05). Compared with group D,the expression of 1L-6.IL-1βand TNF-a mRNA of group E increased significantly (p<0.05)Conclusion:1.Hypothermia could lead to further cardiac function deterioration,The mechanism maybe that the hypothermia could aggravate the inflammation of myocardial tissue in rats of heart failure. 2. By adjusting the transcription expression of IL-6,IL-1βand TNF-a,EPO could inhibit the inflammatory response, so as to improve cardiac function of hypothermia heart failure rats.