Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging
Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging
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使用体内实时成像评估肾缺血/再灌注后他达拉非保护作用的中性粒细胞动态变化
DOI：
10.1097/tp.0000000000003803
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发表时间：
2022
期刊：
影响因子：
6.2
通讯作者：
Nasu Y
中科院分区：
文献类型：
--
作者：
Maruyama Y;Araki M;Kidokoro K;Sogawa Y;Yoshinaga K;Mitsui Y;Sadahira T;Wada K;Watanabe M;Watanabe T;Kashihara N;Nasu Y
背景：中性粒细胞在肾移植和急性肾损伤的缺血/再灌注损伤（IRI）中起主要作用。然而，在活体小鼠肾脏中难以观察到中性粒细胞动力学随时间的变化。我们研究中性粒细胞在IRI在活的小鼠使用新的在体内多光子显微镜成像技术和特点的肾保护作用的选择性磷酸二酯酶5抑制剂，tadalafil.Methods。野生型和内皮型一氧化氮合酶基因敲除小鼠，内皮功能障碍的模型，被用来建立在活的小鼠肾脏在体内实时成像。中性粒细胞用Ly-6 G单克隆抗体标记为绿色，血浆流用BSA标记为红色。术前1小时口服他达拉非。在37 ℃热缺血45分钟后，对两个肾蒂进行再灌注。结果：我们的新方法显示，中性粒细胞在再灌注后几分钟内被困在肾小球中。随着时间的推移，它们逐渐增加，并在小管腔和管周毛细血管中观察到浸润的中性粒细胞。中性粒细胞以3 μm/min的速度在肾小管周围毛细血管丛上滚动。在野生型和内皮型一氧化氮合酶基因敲除小鼠中，他达拉非给药显著减少中性粒细胞流入肾小球。他达拉非组中性粒细胞浸润减少（经流式细胞术证实）导致组织病理学肾小管损伤减少。血管细胞粘附分子1和肾损伤分子1的表达被部分阻止tadalafil.Conclusions.使用一种新的技术有助于阐明再灌注后的中性粒细胞动力学。他达拉非具有抑制肾IRI中性粒细胞浸润的潜力。
Background.Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase 5 inhibitor, tadalafil.Methods.Wild-type and endothelial nitric oxide synthase knockout mice, a model of endothelial dysfunction, were used to establish in vivo real-time imaging in living mouse kidneys. Neutrophils were labeled green with Ly-6G monoclonal antibody, and plasma flow was labeled red with BSA. Tadalafil was administered orally 1 h before surgery. Both kidney pedicles were reperfused after 37 C warm ischemia for 45 min.Results.Our novel approach revealed that neutrophils were trapped in glomerulus within a few minutes after reperfusion. They gradually increased over time and infiltrated neutrophils were observed in the tubular lumen and peritubular capillary. The neutrophils were clearly visualized rolling on peritubular capillary plexus at 3 μm/min. The administration of tadalafil significantly reduced neutrophil influx into the glomerulus in both wild-type and endothelial nitric oxide synthase knockout mice. Reduced neutrophil infiltration in tadalafil groups, which was confirmed by flow cytometry, resulted in histopathologically decreased tubular injury. The expression of vascular cell adhesion molecule 1 and kidney injury molecule 1 was partially prevented by tadalafil.Conclusions.Use of a novel technique contributed to elucidation of neutrophil dynamics after reperfusion. Tadalafil has a potential for inhibiting neutrophil infiltration in renal IRI.
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影响因子：
19.6
作者：
Awad, Alaa S.;Rouse, Michael;Huang, Liping;Vergis, Amy L.;Reutershan, Joerg;Cathro, Helen P.;Linden, Joel;Okusa, Mark D.
通讯作者：
Okusa, Mark D.
影响因子：
8.6
作者：
Jang, Hye Ryoun;Rabb, Hamid
通讯作者：
Rabb, Hamid
DOI：
10.1084/jem.20111493
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Block H;Herter JM;Rossaint J;Stadtmann A;Kliche S;Lowell CA;Zarbock A
通讯作者：
Zarbock A
影响因子：
19.6
作者：
Dong, Xiangyang;Bachman, Lori A.;Miller, Melinda N.;Nath, Karl A.;Griffin, Matthew D.
通讯作者：
Griffin, Matthew D.
影响因子：
19.6
作者：
Bonventre, JV;Zuk, A
通讯作者：
Zuk, A