Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
Clin Sci (Lond). 2010 Jul 23;119(9):385-94. doi: 10.1042/CS20090554.
AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT1 receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P<0.01) and renal Ang-(1-7) was decreased substantially (P<0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased the renal mRNA expression of renin (P<0.05), AT1 receptors (P<0.001) and ACE2 (P<0.05). At 2 and 4 h of reperfusion, renal ACE activity was reduced (P<0.05). On the other hand, renal expression of the Mas receptor was greatly increased at 4 h of reperfusion (P<0.01), which was confirmed by immunohistochemical and Western blot analysis. In conclusion, increased renal expression of the Mas receptor associated with changes in the RAS (renin-angiotensin system)-related peptidases support an important role for the ACE2-Ang-(1-7)-Mas axis in AKI.
血管紧张素 II（AngII）、血管紧张素转换酶（ACE）和 AT1 受体（AngII 型 1 型受体）与肾 I/R（缺血/再灌注）引起的急性肾损伤（AKI）的炎症过程和微血管功能障碍有关。然而，Ang-(1-7)[血管紧张素-(1-7)]、ACE2（血管紧张素转换酶 2）和 Mas 受体也在肾脏疾病模型中发挥作用。因此，在本研究中，我们检查了肾 I/R 中 Ang-(1-7)、ACE2 和 Mas 受体的肾脏特征，并将其与 AngII、ACE 和 AT1 受体进行了比较。雄性 Wistar 大鼠接受左肾切除术和缺血（45 分钟），然后对右肾进行再灌注（2 或 4 小时）。再灌注 4 小时时，肾 AngII 增加（P<0.01），肾 Ang-(1-7) 显著减少（P<0.05），尽管两种血管紧张素的血浆水平均未改变。此外，肾 I/R 降低了肾 renin（P<0.05）、AT1 受体（P<0.001）和 ACE2（P<0.05）的肾 mRNA 表达。再灌注 2 和 4 小时时，肾 ACE 活性降低（P<0.05）。另一方面，再灌注 4 小时时肾 Mas 受体的表达大大增加（P<0.01），免疫组织化学和 Western blot 分析证实了这一点。总之，与 RAS（肾素-血管紧张素系统）相关肽酶相关的肾 Mas 受体表达增加支持 ACE2-Ang-(1-7)-Mas 轴在 AKI 中的重要作用。
