中文摘要：

目的研究血管紧张素Ⅱ（AngⅡ）灌注后大鼠肾脏血管紧张素转换酶2（ACE2）表达的改变及其意义。方法雄性SD大鼠随机分为AngⅡ灌注组（400ng·kg^-1·min^-1）、生理盐水灌注组和健康对照组，每组6只。测定28天内大鼠血压及尿蛋白量变化。于第28天处死动物取肾，观察组织学改变，并用免疫组化、RT-PCR及Western印迹法检测ACE2表达及分布变化；凝胶电泳迁移率分析法（EMSA）检测核因子（NF）-κB的DNA结合活性变化。结果（1）AngⅡ灌注组大鼠血压升高，并出现明显蛋白尿。AngⅡ灌注后第28天，部分肾小球出现轻中度系膜增生，少数有节段性硬化：部分肾小管上皮细胞变性、坏死或萎缩，间质灶性炎性细胞浸润。（2）健康大鼠肾脏ACE2主要分布于肾小管，以近端肾小管刷状缘分布最多。AngⅡ灌注后第28天，肾皮质ACE2 mRNA及蛋白表达均明显下降（P均〈0．05），NF-κB结合活性显著增加（P〈0．05）。相关分析表明，ACE2表达与NF-κB结合活性之间呈负相关（r=-0．64，P〈0．01）。结论AngⅡ灌注可致大鼠肾脏ACE2表达明显下降，后者与肾损害的程度密切相关。肾脏ACE2表达下降可能是AngⅡ引起肾损害的重要机制。

英文摘要：

Objective To evaluate the effect of angiotensin Ⅱ （Ang Ⅱ ） infusion on the expression of angiotensin converting enzyme 2 （ACE2） in rat kidney and its implication in Ang Ⅱ- induced kidney damage. Methods Eighteen male SD rats were randomly assigned to receive either normal saline or Ang Ⅱ （400 ng·kg^-1·min^-1） by osmotic mini-pump, or to be used as normal controls. After the systolic blood pressure was measured, the 24 h urine sample was collected for detection of proteinuria at day 7, 14, 21, 28. Animals were sacrificed at day 28. Serum creatinine and renal pathological changes were observed. Renal nuclear factor （NF）-κB binding activity was evaluated by electrophoretic mobility shift assay （EMSA）. Expression of ACE2 mRNA and protein was analyzed by RT-PCR, Western blot, and immunohistochemical staining. Results （1） Ang Ⅱ- infused rats developed significant hypertension associated with marked proteinuria. At day 28, Ang Ⅱ infusion induced glomerular mesangial proliferation, tubuloepithelial cell damage and inflammatory cell infiltration. （2） ACE2 was present in tubuloepithelial cell, especially in the brush border of proximal convoluted tubular cell. Renal expression of ACE2 mRNA and protein decreased dramatically in Ang Ⅱ-infused rats at day 28 （P〈0.05）. Simultaneously, renal NF-κB binding activity increased markedly （P〈0.05）, and significantly negative correlation was found between the expression of ACE2 and NF-κB binding activity （r=-0.64, P〈0.01）. Conclusion The decrease of renal ACE2 expression may play a critical role in the pathogenesis of Ang Ⅱ-induced kidney damage.