Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway

• DOI: 10.1007/s10753-020-01374-y
• Publication Date: 2020-11-03T12:02:32Z
• Authors: Yang Gao; Kai Kang; Yan-song Liu; Na-na Li; Qiu-yuan Han; Hai-tao Liu; Wei-lan Kong; Xing Zhang; Rui Huang; Zhen-yu Yang; Zhi-dong Qi; Jun-bo Zheng; Ming Li; Hong-liang Wang; Jia-yu Li; Rui-jin Liu; Si-cong Wang; Wei-hua Zhang; Ming-yan Zhao; Kai-jiang Yu
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Blotting, Western; Anti-Inflammatory Agents; NF-kappa B; Apoptosis; Enzyme-Linked Immunosorbent Assay; Acute Kidney Injury; Kidney; 3. Good health; Mice, Inbred C57BL; Mice; Random Allocation; 03 medical and health sciences; Sepsis; In Situ Nick-End Labeling; Splenectomy; Animals; Biomarkers; Dexmedetomidine; Spleen; Signal Transduction

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-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR 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 α7nAChR 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 α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.