Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.
Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.
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TRPV1 通道在缺血/再灌注引起的急性肾损伤中的作用。
DOI：
10.1371/journal.pone.0109842
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gollasch M
中科院分区：
文献类型：
--
作者：
Chen L;Markó L;Kaßmann M;Zhu Y;Wu K;Gollasch M
瞬时受体电位香草素1(TRPV1)阳性感觉神经广泛分布于肾脏，提示TRPV1介导的作用可能参与了病理生理条件下肾功能的调节。刺激TRPV1通道对缺血/再灌注(I/R)所致的急性肾损伤(AKI)具有保护作用。然而，目前尚不清楚抑制这些通道是否对AKI有害。我们用辣椒素(TRPV1激动剂)、辣椒素(TRPV1拮抗剂)对TRPV1通道进行调制，并用TRPV1−/−小鼠研究了TRPV1通道在缺血再灌流所致急性脑损伤中的作用。麻醉C57BL/6小鼠造成肾缺血25min，再灌注24小时。小鼠预先给予辣椒素(0.3 mg/kg体重)或辣椒碱(50 mg/kg体重)。辣椒素可改善AKI的转归，指标包括血清肌酐水平、肾小管损伤程度、中性粒细胞明胶酶相关脂蛋白(NGAL)含量和Ly-6B.2阳性的中性粒细胞。卡萨西平或TRPV1缺乏均不会恶化AKI后的肾功能或组织学改变。肾组织内源性香草素的测定表明，20-羟基二十碳四烯酸(20-HETE)或环氧二十碳三烯酸(EETs)不太可能参与辣椒素对I/R诱导的AKI的有益作用。激活TRPV1通道可改善I/R诱导的AKI，但抑制这些通道并不影响AKI的转归。根据初级感觉神经在肾脏对缺血刺激的反应中的功能，我们的结果可能对去肾神经治疗人类难治性高血压的长期安全性有临床意义。
Transient receptor potential vanilloid 1 (TRPV1) -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist) and using Trpv1−/− mice. Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight) or capsazepine (50 mg/kg body weight). Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL) abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.
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