Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway
Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway
复制标题
α7nAChR-NF-κB 信号通路介导的肾-脾轴参与急性肾损伤的机制
DOI：
10.1007/s10753-020-01374-y
复制
发表时间：
2020-11-03
期刊：
影响因子：
5.1
通讯作者：
Yu, Kai-jiang
中科院分区：
文献类型：
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作者：
Gao, Yang;Kang, Kai;Yu, Kai-jiang
本研究旨在研究脾切除术对右美托咪定激活的胆碱能抗炎通路介导的LPS诱导的AKI缓解的影响。在C57BL/6小鼠中建立脓毒性肾损伤的小鼠模型。将30只C57 BL/6小鼠随机分为对照组、LPS组、右美托咪定+LPS组、脾切除组、脾切除+LPS组和脾切除+右美托咪定+LPS组。HE染色观察各组肾组织病理变化。TUNEL法检测各组细胞凋亡。ELISA法检测各组血清Cr和Cys-C水平。采用qRT-PCR和Western blotting检测各组IL-6、NF-κ B p65、Caspase-3、抗凋亡蛋白Bcl-2、促凋亡蛋白Bax和α 7 nAChR的表达水平。单独使用右美托咪定可减少肾组织中的细胞凋亡;然而，在用右美托咪定处理的小鼠中，脾切除术后细胞凋亡增加。脾切除术减少了循环中促炎细胞因子的产生，对肾脏有保护作用。脾切除术抑制右美托咪定介导的α 7 nAChR通路激活。右美托咪定可有效减轻LPS诱导的肾损伤，脾切除可抑制右美托咪定的抗炎、抗凋亡和肾保护作用。肾-脾轴由α 7 nAChR-NF-κ B信号通路介导，并参与AKI的发生。
This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-kappa B p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and alpha 7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the alpha 7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the alpha 7nAChR-NF-kappa B signaling pathway and is involved in the development of AKI.