α1aar阻滞剂对hrs大鼠肾淤血的保护作用及其机制

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1、α1AAR阻滞剂对HRS大鼠肾淤血的保护作用及其机制作者：张晓刚，贺建宇，万真，李翔，曹永孝，吕毅张晓刚【摘要】目的研究α1A肾上腺素受体(α1AAR)阻滞剂—盐酸坦索罗辛(Tamsulosin)对肝性功能性肾衰竭(HRS)大鼠肾淤血的保护作用及其机制。方法应用D(+)氨基半乳糖盐酸盐[D(+)Galactosaminehydrochloride(GalN)]复制肝性功能性肾衰竭大鼠模型。将建模成功大鼠随机分组，行下腔静脉阻断(OIVC)实验,并给予高选择性α1AAR阻滞剂坦索罗辛术前干预

2、。各组动物分别于下腔静脉阻断前和复流后24h取血测定血清肝肾功生化指标，激光多普勒血流监测仪记录肾皮质和髓质的血流量变化；同时切取肝、肾组织，行HE染色及免疫组化染色，扫描电镜观察肾脏的超微结构。结果HRS大鼠在经历下腔静脉阻断术后，肾皮质、髓质血流明显下降，且较正常大鼠不易恢复，术后肾功明显损伤。坦索罗辛干预大鼠下腔静脉阻断后肾脏淤血改善较明显，肾脏及肾动脉组织α1AR表达均明显降低，病理改变程度较轻。结论经历缺血应激损伤后，HRS大鼠可能由于α1AR高表达所导致的血管收缩反应性增强而容易发生急性肾

3、衰竭。高选择性α1AAR阻滞剂坦索罗辛可显著下调肾动脉及肾小管α1AAR过表达，对HRS大鼠肾脏淤血起到保护作用。【关键词】肝性功能性肾衰竭；缺血性损伤；坦索罗辛17　　ABSTRACT:ObjectiveTostudythemechanismoftheprotectiveeffectofα1AARantagonistTamsulosin(Tam)onrenalischemicinjuryinhepatorenalsyndrome(HRS)rats.MethodsHRSwasinducedinmal

4、eSpragueDawley(SD)ratsbyintraperitonealinjectionofD(+)galactosaminehydrochloride(GalN).ThirtytwoHRSratsweredividedinto3groupsrandomly.Thensurgicalocclusionsoftheinfrahepaticinferiorvenacave(OIVC)wereperformed;Tam,anα1AARantagonist,wasadministereddail

5、ybeforeinjectionofGalN.Duringtheoperation,hemodynamicchangesofthekidneyandliverweremeasuredbylaserDopplerflowmetry(LDF).Serumsampleswerecollectedtomeasureserumlevelsofliverandrenalfunction.Atthesametime,renalandliversampleswereharvestedandstainedbyHEandim

6、munohistochemistry.Otherpartsofthesamplewerefixedwith2.5%glutaraltoobservethecellularultrastructureofrenalandvascularendotheliumbyelectronmicroscope.ResultsOIVCdevelopedmuchsevereischemicinjuryinthekidneyandliverofHRSrats.Therenalcortexbloodperfusion(RCBP

7、)ofHRSratsdecreasedrapidlyafterOIVC,anddidnotreturntobaselineafterreflow.Pathologicalstudyshowedsevereinjuryoftheliverandkidney.However,expressionsofalpha1ARon17renalarteryandkidneywerereducedinthoseratsthathadreceivedTambeforeOIVC.Histologicalexaminatio

8、nofthekidneyalsoshowedfewabnormalities.ConclusionMarkedincreasesofcontractiveresponseofrenalarteryofHRSratsinducedbyupregulationofα1ARmaybeassociatedwithahighriskofprogressiontoacuterenalfailureinHRSratsafterische