氨甲酰化促红细胞生成素对慢性心力衰竭大鼠心脏的保护作用  

Experimental research on cardioprotective effects of carbamylated erythropoietin in rats with chronic heart failure

作　　者：张丽[1] 崔丽君[1] 谈丽丽[1] 王锋[1] 王志禄[2] 李万玲[1] 贾军正[1] 郭文芬[1] 

机构地区：[1]兰州大学第一临床医学院,兰州2730000 [2]兰州大学第一医院心内科,兰州2730000

出　　处：《第三军医大学学报》2011年第1期50-53,共4页Journal of Third Military Medical University

基　　金：甘肃省新药临床前研究重点实验室开放基金(GSKFKT-0707)~~

摘　　要：目的观察氨甲酰化促红细胞生成素(carbamylated erythropoietin,CEPO)对慢性心力衰竭(chronic heartfailure,CHF)大鼠的心脏保护作用并探讨其可能的作用机制。方法 90只Wistar大鼠采用随机抽签法选取10只作为对照组,剩余腹腔注射异丙肾上腺素(isoproterenol,ISO)建立大鼠CHF模型,喂养5周后,将造模成功的大鼠按随机数字表法再分为CEPO组及CHF组,CEPO组腹腔注射CEPO50μg/kg,2次/周,持续4周,CHF组及对照组同期腹腔注射等量生理盐水,4周后检测各组大鼠血流动力学指标、血清肿瘤坏死因子-α(tumor necrosis-alpha,TNF-α)、白介素-6(interlerkin-6,IL-6)水平以及心肌细胞凋亡率的变化。结果与对照组比较,CHF组左室收缩压(LVSP)及左室内压上升/下降最大速率(±dp/dtmax)均显著降低(P<0.05),而左室舒张末压(LVEDP)则显著升高(P<0.05),心率(HR)也显著加快(P<0.05);与CHF组比较,CEPO组LVSP及±dp/dtmax均显著升高(P<0.05),而LVEDP则显著降低(P<0.05),HR也显著减慢(P<0.05)。与对照组比较,CHF组血清TNF-α、IL-6水平及心肌细胞凋亡率均显著升高[TNF-α:(4.01±0.20)vs(8.09±0.09)pg/ml,IL-6:(20.93±1.20)vs(30.26±0.94)pg/ml,心肌细胞凋亡率:(3.80±0.57)%vs(22.35±0.60)%,P<0.05];与CHF组比较,CEPO组血清TNF-α、IL-6水平及心肌细胞凋亡率均显著降低[TNF-α:(8.09±0.09)vs(6.40±0.14)pg/ml,IL-6:(30.26±0.94)vs(25.66±0.74)pg/ml,心肌细胞凋亡率:(22.35±0.60)%vs(13.67±0.36)%,P<0.05]。结论 CEPO可显著改善CHF大鼠的心功能,该作用可能与减轻局部炎症反应及抑制心肌细胞凋亡有关。Objective To investigate the cardioprotective effects of carbamylated erythropoietin（CEPO） in rats with chronic heart failure（CHF） and its possible mechanism.Methods Ten rats were randomly selected from 90 male Wistar rats as control group,and the rest of the Wistar rats were treated by intraperitoneal injection of isoproterenol（ISO） to establish animal models of CHF.After being fed for 5 weeks,the rats were redivided into CEPO group and CHF group.The CEPO group underwent intraperitoneal injection of CEPO（50μg/kg） twice a week for 4 weeks.The CHF group and control group received equivalent amount of saline at the same time.After 4 weeks of CEPO therapy,the hemodynamics,tumor necrosis-alpha（TNF-α） level and interlerkin-6（IL-6） level in serum,and cardiomyocyte apoptosis rate were measured.Results Compared with the control group,the left ventricular systolic pressure（LVSP） and maximum rate of rise/decline of left ventricular pressure（dp/dtmax） decreased significantly in the CHF group（P0.05）,but the left ventricular end-diastolic pressure（LVEDP） and heart rate（HR） increased significantly（P0.05）.Compared with the CHF group,the LVSP and dp/dtmax increased significantly in the CEPO group（P0.05）,but the LVEDP and HR decreased significantly（P0.05）.Compared with the control group,the TNF-α level and IL-6 level in serum and cardiomyocyte apoptosis rate increased significantly in the CHF group（TNF-α： 4.01±0.20 vs 8.09±0.09 pg/ml,IL-6： 20.93±1.20 vs 30.26±0.94 pg/ml,cardiomyocyte apoptosis rate： 3.80±0.57% vs 22.35±0.60%）（P0.05）.Compared with the CHF group,the TNF-α level and IL-6 level in serum and cardiomyocyte apoptosis rate decreased significantly in the CEPO group（TNF-α： 8.09±0.09 pg/ml vs 6.40±0.14 pg/ml,IL-6： 30.26±0.94 pg/ml vs 25.66±0.74 pg/ml,cardiomyocyte apoptosis rate： 22.35±0.60% vs 13.67±0.36%）（P0.05）.Conclusion CEPO can improve cardiac function in rats with CHF,possibly due to its effects of reducing local inf

关 键 词：氨甲酰化促红细胞生成素 慢性心力衰竭 细胞凋亡 肿瘤坏死因子-Α 白介素-6 

分 类 号：R541.6[医药卫生—心血管疾病] R363.27[医药卫生—内科学]