临床医学毕业论文α1aar阻滞剂对hrs大鼠肾淤血的保护作用及其机制.doc

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1、XX大学毕业论文a1AAR阻滞剂对HRS大鼠肾淤血的保护作用及其机制2014年6月25日alAAR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】F1的研究alA肾上腺素受体(alAAR)阻滞剂一盐酸坦索罗辛(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

2、静脉阻断(OIVC)实验，并给予高选择性alAAR阻滞剂坦索罗辛术前干预。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，且较止常大鼠不易恢复，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alAR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

3、鼠可能由于alAR高表达所导致的血管收缩反应性增强而容易发生急性肾衰竭。高选择性alAAR阻滞剂坦索罗辛可显著下调肾动脉及肾小管alAAR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ABSTRACT:ObjectiveTostudythemechanismoftheprotectiveeffectofalAARantagonistTamsulosin(Tam)onrenalischemicinjuryinhepatorenalsyndrome(HRS)rats.

4、MethodsHRSwasinducedinmaleSpragueDawley(SD)ratsbyintraperitonealinjectionofD(+)galactosaminehydrochloride(GalN).ThirtytwoHRSratsweredividedinto3groupsrandomly.Thensurgicalocclusionsoftheinfrahcpaticinferiorvenaeave(OIVC)wereperformed;Tam,analAARantagonist,

5、wasadministereddailybeforeinjectionofGalN.Duringtheoperation,hemodynamicchangesofthekidneyandliverweremeasuredbylaserDopplerflowmetry(LDF).Serumsampleswerecollectedtomeasureserumlevelsofliverandrenalfunction.Atthesametime,renalandliversampleswereharvesteda

6、ndstainedbyHEandimmunohistochemistry.Otherpartsofthesamplewerefixedwith2.5%glutaraltoobservethecellularultrastructurcofrenalandvascularendotheliumbyelectronmicroscope.ResultsOIVCdevelopedmuchsevereischemicinjuryinthekidneyandliverofHRSrats.Therenalcortexbl

7、oodperfusion(RCBP)ofHRSratsdecreasedrapidlyafterOIVC,anddidnotreturntobaselineafterreflow・Pathologicalstudyshowedsevereinjuryoftheliverandkidney.However,expressionsofalpha1ARonrenalarteryandkidneywerereducedinthoseratsthathadreceivedTambeforeOIVC.Histologi

8、calexaminationofthekidneyalsoshowedfewabnormalities.ConclusionMarkedincreasesofcontractiveresponseofrenalarteryofHRSratsinducedbyupregulationofalARmaybeassociatedwithahighriskofprogressiontoacuterenalfailurei