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Am J Transl Res. 2019 Apr 15;11(4):2540-2549. eCollection 2019.

Effect of splenectomy on attenuation of LPS-induced AKI through GTS-21-induced cholinergic anti-inflammatory pathway.

Author information

1
Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
2
Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University Harbin 150001, China.
3
Department of Critical Care Medicine, The Cancer Hospital of Harbin Medical University Harbin 150081, China.
4
Department of Pathophysiology, Harbin Medical University Harbin 150086, China.
5
Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University Ministry of Education Harbin 150086, China.
6
The Centre for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Harbin 150086, China.

Abstract

This work was undertaken to explore the role of splenectomy on attenuation of lipopolysaccharide (LPS)-induced acute kidney injury (AKI) through GTS-21-induced cholinergic anti-inflammatory pathway. C57BL/6 mice were used to construct models of sepsis-induced renal injury. HE, Tunel and blood assays were used to determine the success of the model. The animals were examined after splenectomy with or without LPS and GTS-21+LPS treatments. The pathological changes and apoptosis in the renal tissue were detected using HE and Tunel assays. The contents of creatinine (Cr) and cystatin-C (Cys-C) were measured using ELISA. The expression of IL-6, NF-kB p65, Caspase-3, anti-apoptotic protein Bcl-2, apoptotic protein Bax and α7nAChR was quantified using qRT-PCR. The expression of Bcl-2, Bax, Caspase-3, IL-6, NF-kB p65, α7nAChR and p-STAT3 was using assessed using Western blot analysis. HE, Tunel, BUN and serum creatinine (SC) assay showed that renal injury models were successfully established. Compared with the control, the apoptosis in the LPS group was significantly increased and decreased after GTS-21 treatment. However, splenectomy combined with GTS-21 increased the apoptosis, indicating that splenectomy could partially offset the anti-apoptosis effect of GTS-21. In animals treated with LPS, the contents of Cr and Cys-C increased significantly. These contents reduced following GTS-21 treatment, but increased after splenectomy. After LPS treatment, the expression of IL-6, NF-kB p65, p-STAT3, Caspase-3 and Bax was significantly up-regulated, while the expression of α7nAChR and Bcl-2 significantly down-regulated. Compared with LPS treated mice, splenectomy reduced the expression of IL-6, NF-kB p65 and p-STAT3, suggesting that splenectomy inhibits the activation of α7nAChR pathway by the GTS-21. It is clear that GTS-21 effectively attenuates LPS-induced renal injury; splenectomy suppresses the anti-inflammatory and anti-apoptosis activity and renal protective effect of GTS-21. On other hand, splenectomy reduces the production of inflammatory cytokines in the circulation, and has certain protective effect on the kidney. Therefore, the impact of splenectomy on LPS-induced AKI depends on the strength of the two aspects.

KEYWORDS:

AKI; GTS-21; LPS; Splenectomy; apoptosis; cholinergic anti-inflammatory pathway; inflammatory reaction

PMID:
31105861
PMCID:
PMC6511767

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