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Ameliorative effect of AT2R and ACE2 activation on ischemic renal injury associated cardiac and hepatic dysfunction
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-09-23 , DOI: 10.1016/j.etap.2020.103501
Nisha Sharma 1 , Anil Bhanudas Gaikwad 1
Affiliation  

This study explored the role of the depressor arm of renin-angiotensin system (RAS) on ischemic renal injury (IRI)-associated cardio-hepatic sequalae under non-diabetic (ND) and diabetes mellitus (DM) conditions. Firstly, rats were injected with Streptozotocin (55 mg/kg i.p.) to develop DM. ND and DM rats underwent Bilateral IRI followed by 24 h of reperfusion. Further, ND and DM rats were subjected to AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator- Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) per se or its combination therapy. As results, IRI caused cardio-hepatic injuries via altered oxidant/anti-oxidant levels, elevated inflammatory events, and altered protein expressions of ACE, ACE2, Ang II, Ang-(1–7) and urinary AGT. However, concomitant therapy of AT2R agonist and ACE2 activator exerts a protective effect in IRI-associated cardio-hepatic dysfunction as evidenced by inhibited oxidative stress, downregulated inflammation, and enhanced cardio-hepatic depressor arm of RAS under ND and DM conditions.



中文翻译:

AT2R 和 ACE2 激活对缺血性肾损伤相关心肝功能障碍的改善作用

本研究探讨了肾素-血管紧张素系统 (RAS) 的降压臂在非糖尿病 (ND) 和糖尿病 (DM) 条件下对缺血性肾损伤 (IRI) 相关心肝后遗症的作用。首先,给大鼠注射链脲佐菌素 (55 mg/kg ip ) 以发展 DM。ND 和 DM 大鼠接受双侧 IRI,然后再灌注 24 小时。此外,ND 和 DM 大鼠接受 AT2R 激动剂 - 化合物 21(C21)(0.3 毫克/千克/天,ip)或 ACE2 激活剂 - 醋酸二胺(Dize),(5 毫克/千克/天,口服) 本身或其联合疗法。结果,IRI 通过改变氧化/抗氧化水平、增加炎症事件以及改变 ACE、ACE2、Ang II、Ang-(1-7) 和尿 AGT 的蛋白质表达而引起心肝损伤。然而,在 ND 和 DM 条件下,AT2R 激动剂和 ACE2 激活剂的联合治疗在 IRI 相关的心肝功能障碍中发挥了保护作用,这可以通过抑制氧化应激、下调炎症和增强 RAS 的心肝抑制臂来证明。

更新日期:2020-09-29
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