人工重组促红细胞生成素导致高血压机制的研究  

Studyonmechanismofhypertensionrelatedtor┐HuEPOinrats

作　　者：董菲[1] 郝传明[1] 顾勇[1] 陆福明[1] 林善锬[1] 

机构地区：[1]上海医科大学附属华山医院肾病科

出　　处：《中华肾脏病杂志》1996年第2期67-71,共5页Chinese Journal of Nephrology

摘　　要：对人工重组促红细胞生成素（ｒ－ＨｕＥＰＯ）替代治疗中出现高血压的机制进行了研究。观察了使用ｒ－ＨｕＥＰＯ前后发生高血压（Ａ组）与未发生高血压组（Ｂ组）之间心脏血流动力学、血液粘滞度以及血管活性物质（肾素ＰＲＡ，血管紧张素ＡⅡ，醛固酮ＡＬＤ，内皮素ＥＴ、心钠素ＡＮＰ，去甲肾上腺素ＮＡ）等的血浆浓度和离体阻力血管条对上述活性物质敏感性的改变。结果发现：Ａ组与Ｂ组的患者之间心脏血流动力学无明显差异。随着贫血的纠正，Ｈｃｔ升高，患者的血液全血粘滞度也上升，二组的血液粘滞度随时间上升曲线几乎重叠。使用ＥＰＯ前后血浆ＰＲＡ，ＡⅡ，ＡＬＤ无明显改变，二组间也无统计学差异。为了排除遗传、环境等诸因素的影响，又观察了ＳＤ大鼠使用ＥＰＯ后血浆ＰＲＡ，ＡⅡ，ＡＮＰ和ＥＴ值，与对照组相比无明显升高。使用ＥＰＯ鼠肠系膜前动脉对ＥＴ，ＮＡ收缩作用较对照鼠明显升高，但ＥＰＯ鼠动脉对ＡⅡ的收缩作用却低于对照鼠，表现为其浓度－效应曲线的右移。因此使用ＥＰＯ后阻力血管对ＥＴ，ＮＡ等缩血管物质的反应性过高可能是造成高血压的重要原因之一，而心脏血流动力学，血液粘滞度在其中不起主要作用。Themechanismofhypertensionassociatedwithr-HuEPOtreatmenthasnotbeencompletelyunder-stood.Inthisstudy,30caseswithanemiareceivedr-HuEPOtherapywereexamined.7outofthe30patientsde-velopedhypertension,nosignificantdiferenceoftheHctrisingrateandwholebloodviscosityratewereobservedbetwenhypertensivepatients(groupA)andnon-hypertensivepatients(groupB),alsotherewasnosignificantdiferenceinplasmareninactivity(PRA),angiotensinⅡ(AⅡ),aldosterone(ALD)betweenthesetwogroupsbeforeandafterr-HuEPOtreatment.Evaluatedbyechocardiography,thestrokevolume(SV)andcardiacoutput(CO)wasfounddecreasingslightlyingroupAandincreasingingroupBafterthetreatment.Intheratstudy,theexperimentalSDrats(C)receivedsubcutaneousr-HuEPO150U/kgtiw,andthecontrolrats(D)receivedthesamevolumeof0.9%NaCl.Threeweekslater,bloodpresure(BP)andHctraisedremarkablyinCcomparedwithD.Therewasnodiferenceinplasmaendothelin(ET),ANP,PRA,AⅡlevelbetweenCandD.WhilethevasoconstrictiveefectofETandNAinCwasmoreprominentthanthatinD.TheEC50oftheanteriormesentericarteriesinCwasapparentlylowerthanthatinD.ButthesensitivityofarteriestoAⅡinCwaslowerthanthatinD.Theresultsalsodemonstratedthatther-HuEPOitselfhadnodirectcontractileefectbothonrat'santeriormesentericandaorticarteries.Thefindingsuggestedthatthevasoactivefactorsplayanimportantroleinthepathogenesisofhypertensionafterr-HuEPOtreatment.

关 键 词：红细胞生成素 高血压 R-HUEPO 

分 类 号：R973.3[医药卫生—药品] R544.102[医药卫生—药学]