Cao Wei, Li Aiqing, Li Jiawen, Wu Chunyi, Cui Shuang, Zhou Zhanmei, Liu Youhua, Wilcox Christopher S, Hou Fan Fan
1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
2 Hypertension, Kidney and Vascular Research Center, Georgetown University , Washington, District of Columbia.
Antioxid Redox Signal. 2017 Sep 1;27(7):415-432. doi: 10.1089/ars.2016.6827. Epub 2017 Jan 31.
A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury.
Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p < 0.05). Ischemia-reperfusion-induced renal damage and dysfunction persisted after controlling blood pressure with hydralazine.
This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage.
These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.
急性肾损伤中存在肾-脑相互作用，但机制尚不清楚。由于我们最近描述了一种肾-脑反射，我们检验了以下假设：肾缺血再灌注损伤（IRI）激活一种交感反射，该反射将肾和脑的肾素-血管紧张素轴联系起来，以促进氧化应激和损伤进展。
双侧缺血再灌注激活了肾内和脑内的肾素-血管紧张素系统（RAS），但未激活循环中的RAS，增加了肾和脑交感神经调节区域的交感神经活动，并诱导了脑炎症和肾损伤。用辣椒素进行选择性肾传入神经去支配或肾去神经支配显著减弱了IRI诱导的中枢RAS激活和脑炎症。通过脑室内（ICV）给予氯沙坦或Tempol对RAS或氧化应激进行中枢阻断，分别使肾缺血损伤评分降低了65%或58%，而选择性肾传入神经去支配或通过ICV可乐定降低交感神经张力分别使评分降低了42%或52%（所有p<0.05）。用肼屈嗪控制血压后，缺血再灌注诱导的肾损伤和功能障碍仍然存在。
本研究发现了缺血性肾与脑之间一种新的反射途径，该途径维持肾氧化应激和局部RAS激活，以促进持续性肾损伤。
这些数据表明，肾和脑的肾素-血管紧张素轴通过缺血再灌注激活的肾-脑交感反射相互联系，这导致了缺血再灌注诱导的脑炎症和急性肾损伤的恶化。《抗氧化.氧化还原信号》27, 415 - 432。
