Vagus nerve stimulation even after injury ameliorates cisplatin-induced nephropathy via reducing macrophage infiltration
Vagus nerve stimulation even after injury ameliorates cisplatin-induced nephropathy via reducing macrophage infiltration
复制标题
即使在损伤后迷走神经刺激也可以通过减少巨噬细胞浸润来改善顺铂诱发的肾病
DOI：
10.1038/s41598-020-66295-0
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发表时间：
2020
影响因子：
4.6
通讯作者：
Inagi Reiko
中科院分区：
文献类型：
--
作者：
Uni Rie;Inoue Tsuyoshi;Nakamura Yasuna;Fukaya Daichi;Hasegawa Sho;Wu Chia-Hsien;Fujii Rie;Surattichaiyakul Bongkod;Peerapanyasut Wachirasek;Ozeki Atsuko;Akimitsu Nobuyoshi;Wada Youichiro;Nangaku Masaomi;Inagi Reiko
在肾缺血再灌注损伤模型中，通过迷走神经刺激（VNS）预先激活胆碱能抗炎途径（CAP）的效果已被报道。然而，目前还没有报道表明迷走神经刺激在损伤后的有效性。我们研究了VNS在顺铂肾病模型中的肾保护作用。C57BL/6小鼠注射顺铂，24小时后行VNS。顺铂给药后72小时评估肾功能、组织学和肾损伤标志物（Kim-1）。为了进一步探讨脾脏和脾脏巨噬细胞的作用，我们研究了选择性α7烟碱乙酰胆碱受体激动剂GTS-21对巨噬细胞进行CAP、脾切除和过继性转移的关键作用。VNS治疗明显抑制顺铂所致肾损伤。脾切除术消除了这种作用，而过继性转移gts -21处理的巨噬细胞改善了肾脏预后。VNS还降低了细胞因子和趋化因子的表达，包括CCL2， CCL2是一种有效的趋化因子，吸引单核细胞/巨噬细胞，并伴有浸润巨噬细胞数量的下降。综上所述，在顺铂诱导的肾病模型中，即使在损伤后，刺激CAP也能保护肾脏。考虑到VNS的可行性和抗炎作用，研究结果表明VNS可能是一种有前景的治疗急性肾损伤的工具。
The efficacy of prior activation of an anti-inflammatory pathway called the cholinergic anti-inflammatory pathway (CAP) through vagus nerve stimulation (VNS) has been reported in renal ischemia-reperfusion injury models. However, there have been no reports that have demonstrated the effectiveness of VNS after injury. We investigated the renoprotective effect of VNS in a cisplatin-induced nephropathy model. C57BL/6 mice were injected with cisplatin, and VNS was conducted 24 hours later. Kidney function, histology, and a kidney injury marker (Kim-1) were evaluated 72 hours after cisplatin administration. To further explore the role of the spleen and splenic macrophages, key players in the CAP, splenectomy, and adoptive transfer of macrophages treated with the selective α7 nicotinic acetylcholine receptor agonist GTS-21 were conducted. VNS treatment significantly suppressed cisplatin-induced kidney injury. This effect was abolished by splenectomy, while adoptive transfer of GTS-21-treated macrophages improved renal outcomes. VNS also reduced the expression of cytokines and chemokines, including CCL2, which is a potent chemokine attracting monocytes/macrophages, accompanied by a decline in the number of infiltrating macrophages. Taken together, stimulation of the CAP protected the kidney even after injury in a cisplatin-induced nephropathy model. Considering the feasibility and anti-inflammatory effects of VNS, the findings suggest that VNS may be a promising therapeutic tool for acute kidney injury.
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影响因子：
6.1
作者：
Seok, Su Jin;Lee, Eun Soo;Chung, Choon Hee
通讯作者：
Chung, Choon Hee
DOI：
10.2215/cjn.12811211
发表时间：
2012-05-01
影响因子：
9.8
作者：
Okusa, Mark D.;Molitoris, Bruce A.;Star, Robert A.
通讯作者：
Star, Robert A.
肾损伤增强肾 G-CSF 表达并调节体内粒细胞生成和人中性粒细胞 CD177
影响因子：
4.6
作者：
J. Volkmann;J. Schmitz;J. Nordlohne;L. Dong;A. Helmke;P. Sen;S. Immenschuh;W. Bernhardt;W. Gwinner;J. Bräsen;R. Schmitt;H. Haller;S. von Vietinghoff
通讯作者：
S. von Vietinghoff
影响因子：
13.6
作者：
Dutta, Rajesh K.;Kondeti, Vinay K.;Kanwart, Yashpal S.
通讯作者：
Kanwart, Yashpal S.
影响因子：
15.9
作者：
Inoue, Tsuyoshi;Abe, Chikara;Okusa, Mark D.
通讯作者：
Okusa, Mark D.