Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway
Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway
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DOI：
10.1681/asn.2013010084
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发表时间：
2013-09-01
影响因子：
13.6
通讯作者：
Okusa, Mark D.
中科院分区：
文献类型：
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作者：
Gigliotti, Joseph C.;Huang, Liping;Okusa, Mark D.
阿基影响生活质量和医疗保健成本，是死亡率的独立风险因素。目前，阿基的有效治疗方案很少。在这里，我们描述了一种非药理学的，非侵入性的，基于超声的方法来预防小鼠肾缺血再灌注损伤，这是一种人类阿基模型。我们在肾缺血前24小时将麻醉小鼠暴露于超声方案。再灌注24小时后，与假手术治疗的小鼠相比，超声治疗的小鼠表现出保留的肾脏形态和功能。肾缺血前超声暴露可减少肾组织中CD 11b（+）Ly 6 G（高）中性粒细胞和CD 11b（+）F4/80（高）髓样细胞的蓄积。此外，脾切除术和过继转移研究表明，脾脏和CD 4（+）T细胞介导的超声波的保护作用。最后，阻断或遗传缺陷的7烟碱乙酰胆碱受体废除了超声波的保护作用，这表明胆碱能抗炎途径的参与。总之，这些结果表明，基于超声的治疗可能具有预防阿基的治疗潜力，可能是通过刺激脾脏抗炎途径。
AKI affects both quality of life and health care costs and is an independent risk factor for mortality. At present, there are few effective treatment options for AKI. Here, we describe a nonpharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury in mice, which is a model for human AKI. We exposed anesthetized mice to an ultrasound protocol 24 hours before renal ischemia. After 24 hours of reperfusion, ultrasound-treated mice exhibited preserved kidney morphology and function compared with sham-treated mice. Ultrasound exposure before renal ischemia reduced the accumulation of CD11b(+)Ly6G(high) neutrophils and CD11b(+)F4/80(high) myeloid cells in kidney tissue. Furthermore, splenectomy and adoptive transfer studies revealed that the spleen and CD4(+) T cells mediated the protective effects of ultrasound. Last, blockade or genetic deficiency of the 7 nicotinic acetylcholine receptor abrogated the protective effect of ultrasound, suggesting the involvement of the cholinergic anti-inflammatory pathway. Taken together, these results suggest that an ultrasound-based treatment could have therapeutic potential for the prevention of AKI, possibly by stimulating a splenic anti-inflammatory pathway.