α1AAR阻滞剂对HRS大鼠肾淤血的保护作用及其机制.doc

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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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(+)Galactosamine hydrochloride(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。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
ABSTRACT: Objective To study the mechanism of the protective effect of α1AAR antagonist Tamsulosin (Tam) on renal ischemic injury in hepatorenal syndrome (HRS) rats. Methods HRS was induced in male SpragueDawley (SD) rats by intraperitoneal injection of D(+)galactosamine hydrochloride (GalN). Thirtytwo HRS rats were divided into 3 groups randomly. Then surgical occlusions of the infrahepatic inferior vena cave (OIVC) were performed; Tam, an α1AAR antagonist, was administered daily before injection of GalN. During the operation, hemodynamic changes of the kidney and liver were measured by laser Doppler flowmetry (LDF). Serum samples were collected to measure serum levels of liver and renal function. At the same time, renal and liver samples were harvested and stained by HE and immunohistochemistry. Other parts of the sample were fixed with % glutaral to observe the cellular ultrastructure of renal and vascular endothelium by electron microscope. Results OIVC developed much severe ischemic injury in the kidney and liver of HRS rats. The renal cortex blood perfusion (RCBP) of HRS rats decreased r
apidly after OIVC, and did not return to baseline after reflow. Pathological study showed severe injury of the liver and kidney. However, expressions of alpha1 AR on renal artery and kidney were reduced in those rats that h