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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）在早期慢性肾病小鼠模型中的影响

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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 ? nephrectomy (? Nx) mouse model of chronic kidney disease (CKD). Male FVB mice underwent sham surgery (Sham) or ? Nx and were administered either vehicle, the ACE2 inhibitor MLN-4760 (MLN), the AT1 receptor antagonist losartan, MLN plus losartan, or ANG-(1–7) for 4 wk. In ? 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 ? Nx mice treated with MLN, kidney levels of ANG II were significantly increased, compared with Sham. ? 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 ? Nx mice did not affect BP or FITC-inulin clearance but significantly increased albuminuria compared with ? Nx alone, an effect reversed by losartan. Treatment of ? 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 ? Nx. Inhibition of ACE2 in ? Nx mice increases albuminuria via an AT1 receptor-dependent mechanism, independent of BP. In contrast, ANG-(1–7) does not affect albuminuria after ? Nx. We propose that endogenous ACE2 is renoprotective in CKD.
机译：血管紧张素转换酶2（ACE2）在肾脏中的高水平表达，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）的影响吗？肾切除术（γNX）慢性肾病（CKD）的小鼠模型。雄性FVB小鼠接受了假手术（假）或？ NX并施用载体，ACE2抑制剂MLN-4760（MLN），AT1受体拮抗剂氯沙坦，MLN加氯沙坦，或Ang-（1-7），持续4WK。在 ？与msh相比，肾脏皮质αce2蛋白表达具有或没有MLN的肾小球小鼠显着降低4周。抑制ACE2导致肾皮质ace2活性降低。肾脏皮质ACE表达和活性在小鼠组之间没有差异。在 ？用MLN处理的NX小鼠，肾脏水平Ang II的肾脏水平显着增加，与假相比。还NX诱导温和但不足的血压（BP）的增加，FITC-胆蛋白清除的50％降低，尿白蛋白排泄的显着增加。 ACE2抑制在？ NX小鼠不影响BP或FITC- inulin的间隙，但与蛋白尿相比显着增加？单独的NX，由洛萨顿逆转的效果。治疗？ NX小鼠具有Ang-（1-7）增加肾脏和血浆水平的Ang-（1-7），但没有改变Bp，Fitc-inulin清除或尿白蛋白排泄，并且它增加了相对髓鞘区域。这些数据表明，肾脏ACE2在早期下调之后的下调？ NX。抑制ACE2？ NX小鼠通过AT1受体依赖性机制增加白蛋白尿，与BP无关。相比之下，Ang-（1-7）不影响白蛋白尿后？ NX。我们提出内源性ACE2在CKD中进行了更新保护。

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