促红细胞生成素对高脂血症大鼠的降脂作用及机制研究

The Lipid-lowering Eff ect and Mechanism of Erythropoietin on Hyperlipidemia Rats

目的:探讨促红细胞生成素(EPO)对高脂血症大鼠血脂水平的调节及作用机制。方法:将SD大鼠随机分为正常对照组、高脂血症模型组、EPO组,每组8只。正常对照组大鼠给予基础饲料,模型组及EPO组大鼠给予高脂饲料,连续喂养8周。8周后EPO组按1000 U·kg^(-1)腹腔注射EPO,每周3次,正常对照组和高脂血症模型组大鼠腹腔注射生理盐水。给药4周后,检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平及炎症因子白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量,肝脏组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,血液流变学检测血液黏度相关指标,蛋白免疫印迹(Western Blotting)检测肝脏组织SOD1、IL-1β的蛋白表达。结果:EPO不影响高脂血症大鼠体质量增长,可显著降低高脂血症大鼠TC、TG、LDL-C水平,升高HDL-C水平;EPO可改善高脂血症大鼠血液黏滞性,降低低切变率、中切变率、高切变率全血黏度和中切变率全血还原黏度、血沉等指标;还可明显降低高脂血症大鼠肝脏组织MDA含量,升高SOD活性,降低血清IL-1β和TNF-α水平,增强肝脏组织SOD1蛋白表达,减弱IL-1β蛋白表达。结论:EPO可显著改善高脂血症大鼠的血脂水平,其降脂作用机制可能与改善血液黏滞性、减轻肝脏氧化损伤和炎症反应有关。

Objective:To investigate the regulation and mechanism of erythropoietin(EPO)on blood lipid level in hyperlipidemia rats.Methods:SD rats were randomly divided into control group,hyperlipidemia model group and EPO group,with 8 rats in each group.Basic diet was provided to the rats in control group,and high-fat diet was provided to the rats in model group and EPO group for 8 weeks.After 8 weeks,the rats in EPO group were intraperitoneally injected with 1000 U∙kg^(-1) EPO three times per week,and the rats in control group and hyperlipidemia model group were intraperitoneally injected with normal saline.Subsequent to 4 weeks of administration,the levels of serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and inflammatory factors(IL-1β,TNF-α)were detected.The malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in liver tissue were measured,hemorheology was used to detect blood viscosity related indexes,and the protein expression of SOD1 and IL-1βin liver tissue were detected by using Western Blotting.Results:EPO did not affect the weight gain of hyperlipidemia rats,but it signifi cantly reduced the levels of TC,TG and LDL-C and increased the level of HDL-C.EPO ameliorated the blood viscosity of hyperlipidemia rats and reduced the indexes such as low shear rate,medium shear rate,high shear rate of whole blood viscosity,medium shear rate of whole blood reduction viscosity and erythrocyte sedimentation rate.EPO signifi cantly reduced the content of MDA in liver tissue,increased the activity of SOD and reduced the serum levels of IL-1βand TNF-αin hyperlipidemia rats.EPO enhanced the protein expression of SOD1 and decreased the protein expression of IL-1βof liver tissue.Conclusion:EPO could signifi cantly improve the blood lipid level of hyperlipidemia rats,and its lipid-lowering mechanism might be related to improved blood viscosity,reduced liver oxidative damage and inflammatory response.