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首页> 外文期刊>American Journal of Physiology >Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease.
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Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease.

机译：ACE2和血管紧张素-（1-7）在早期慢性肾脏疾病小鼠模型中的作用。

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Angiotensin-converting enzyme 2 (ACE2) is expressed at high levels in the kidney and converts angiotensin II (ANG II) to ANG-(1-7). We studied the effects of ACE2 inhibition and ANG-(1-7) in the (5/6) nephrectomy ((5/6) Nx) mouse model of chronic kidney disease (CKD). Male FVB mice underwent sham surgery (Sham) or (5/6) Nx and were administered either vehicle, the ACE2 inhibitor MLN-4760 (MLN), the AT(1) receptor antagonist losartan, MLN plus losartan, or ANG-(1-7) for 4 wk. In (5/6) Nx mice with or without MLN, kidney cortical ACE2 protein expression was significantly decreased at 4 wk, compared with Sham. Inhibition of ACE2 caused a decrease in renal cortical ACE2 activity. Kidney cortical ACE expression and activity did not differ between groups of mice. In (5/6) Nx mice treated with MLN, kidney levels of ANG II were significantly increased, compared with Sham. (5/6) Nx induced a mild but insignificant increase in blood pressure (BP), a 50% reduction in FITC-inulin clearance, and a significant increase in urinary albumin excretion. ACE2 inhibition in (5/6) Nx mice did not affect BP or FITC-inulin clearance but significantly increased albuminuria compared with (5/6) Nx alone, an effect reversed by losartan. Treatment of (5/6) Nx mice with ANG-(1-7) increased kidney and plasma levels of ANG-(1-7) but did not alter BP, FITC-inulin clearance, or urinary albumin excretion, and it increased relative mesangial area. These data indicate that kidney ACE2 is downregulated in the early period after (5/6) Nx. Inhibition of ACE2 in (5/6) Nx mice increases albuminuria via an AT(1) receptor-dependent mechanism, independent of BP. In contrast, ANG-(1-7) does not affect albuminuria after (5/6) Nx. We propose that endogenous ACE2 is renoprotective in CKD.
机译：血管紧张素转化酶2（ACE2）在肾脏中高水平表达，并将血管紧张素II（ANG II）转化为ANG-（1-7）。我们研究了ACE2抑制和ANG-（1-7）在慢性肾脏病（CKD）的（5/6）肾切除术（（5/6）Nx）小鼠模型中的作用。对雄性FVB小鼠进行假手术（Sham）或（5/6）Nx，并给予媒介物，ACE2抑制剂MLN-4760（MLN），AT（1）受体拮抗剂洛沙坦，MLN加洛沙坦或ANG-（1 -7）4周。与Sham相比，在有或没有MLN的（5/6）Nx小鼠中，第4周时肾皮质ACE2蛋白表达显着降低。抑制ACE2会导致肾皮质ACE2活性降低。两组小鼠之间的肾皮质ACE表达和活性没有差异。与Sham相比，在（5/6）只MLN治疗的Nx小鼠中，ANG II的肾脏水平显着增加。 （5/6）Nx引起血压（BP）轻度但微不足道的增加，FITC-菊粉清除率降低50％，尿白蛋白排泄量显着增加。与单独的（5/6）Nx相比，（5/6）Nx小鼠中的ACE2抑制不影响BP或FITC-菊粉清除率，但显着增加白蛋白尿，这一作用被氯沙坦所逆转。用ANG-（1-7）处理（5/6）Nx小鼠可增加肾和血浆ANG-（1-7）的水平，但不会改变BP，FITC-菊粉清除率或尿白蛋白排泄，并且相对系膜区。这些数据表明，肾脏ACE2在（5/6）Nx之后的早期被下调。在（5/6）Nx小鼠中ACE2的抑制通过AT（1）受体依赖性机制（独立于BP）增加蛋白尿。相反，ANG-（1-7）在（5/6）Nx后不影响蛋白尿。我们提出内源性ACE2在CKD中具有肾脏保护作用。

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