Vagus nerve stimulation ameliorates sepsis-induced acute kidney injury in rat

doi:10.3969/j.issn.1006-7795.2024.02.005

Abstract

Abstract: Objective To evaluate the influence of vagus nerve stimulation on renal function in septic rats and explore its mechanism. Methods Forty male SD rats were divided into four groups：sham group, sepsis group, vagus nerve stimulation（VNS）group, and alpha7 nicotinic acetylcholine receptors（α7nAChR）antagonist group（n=10）. Rats in sham injury group only underwent laparotomy to expose the cecum, and then the cecum was returned to the abdominal cavity. Sepsis rat model was constructed by cecal ligation and perforation（CLP）. Rats in VNS group were given electrical stimulation on left cervical vagus nerve for 20 min after CLP. Rats in α7nAChR antagonist group were intraperitoneally injected with 2 mg/kg methyllycaconitine（MLA） at 30 min before CLP. At 24 h after CLP, serum of rats was collected to detect levels of blood urea nitrogen（BUN）, serum creatinine（Scr）, tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）by biochemical and enzyme-linked immunosorbent assay（ELISA）. The 24 h urine volume of each rat was collected, and the 24 h urine volume per kilogram body weight of each rat was calculated. Urinary neutrophil gelatinase-associated lipocalin（NGAL）and kidney injury molecule-1（KIM-1）were analyzed by ELISA. hematoxylin-eosin (HE) staining and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed to evaluate renal histopathological changes and tubule cell apoptosis. Results ① The levels of BUN, Scr, TNF-α and IL-6 of rats in sepsis group were significantly higher than those in sham group and VNS group（P<0.01）. ② The 24 h urine volume per kilogram body weight of rats in sepsis group was significantly lower than that in sham group and VNS group （P<0.01）. ③ The levels of urinary NGAL and KIM-1 in sepsis group were significantly higher than those in sham group and VNS group（P<0.01）. ④ As compared with those of rats in sham group and VNS group, the renal histological damage score and the renal tubule apoptotic cell coun of rats in sepsis group were significantly increased（P<0.01）. ⑤ Scr, BUN, TNF-α, IL-6, urinary NGAL, urinary KIM-1, 24 h urine volume per kilogram, renal histological damage score, and renal tubule cell apoptosis count in sepsis group showed no significant difference from α7nAChR antagonist group（P>0.05）. Conclusion Electrical stimulation of vagus nerve can significantly alleviate sepsis-induced acute kidney injury in rats，through the activation of α7nAChR dependent cholinergic anti-inflammatory pathway.

Key words: sepsis, acute kidney injury, vagus nerve stimulation, cholinergic anti-inflammatory pathway, alpha 7 nicotinic acetylcholine receptors

CLC Number:

R631

Li Juncong, Zhao Song, Yu Kai, Han Yuzhen, Guo Fangxing, Li Wenxiong. Vagus nerve stimulation ameliorates sepsis-induced acute kidney injury in rat[J]. Journal of Capital Medical University, 2024, 45(2): 201-206.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2024.02.005

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2024/V45/I2/201

References

［1］ Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021［J］. Intensive Care Med, 2021, 47(11):1181-1247.
［2］ Liu D, Huang S Y, Sun J H, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options［J］. Mil Med Res, 2022, 9(1):56.
［3］ Kelly M J, Breathnach C, Tracey K J, et al. Manipulation of the inflammatory reflex as a therapeutic strategy［J］. Cell Rep Med, 2022 3(7):100696.
［4］ Pavlov V A, Chavan S S, Tracey K J. Molecular and functional neuroscience in immunity［J］. Annu Rev Immunol, 2018, 36:783-812.
［5］ Luca C, Salvatore F, Vincenzo D P, et al. Anesthesia protocols in laboratory animals used for scientific purposes［J］. Acta Biomed, 2018, 89(3):337-342.
［6］ Rittirsch D, Huber-Lang M S, Flierl M A, et al. Immunodesign of experimental sepsis by cecal ligation and puncture［J］. Nat Protoc, 2009, 4(1):31-36.
［7］ Chen H, Feng Z, Min L X, et al. Vagus nerve stimulation reduces neuroinflammation through microglia polarization regulation to improve functional recovery after spinal cord injury［J］. Front Neurosci, 2022, 16:813472.
［8］ Wei X, Wu Y, Tang H, et al. CP-25 ameliorates methotrexate induced nephrotoxicity via improving renal apoptosis and methotrexate excretion［J］. J Pharmacol Sci, 2021, 146(1):21-28.
［9］ Rafieian-Kopaei M, Nasri H, Nematbakhsh M, et al. Erythropoietin ameliorates genetamicin-induced renal toxicity: a biochemical and histopathological study［J］. J Nephropathol, 2012, 1(2):109-116.
［10］ Shi X, Li J, Han Y, et al. The α7 nicotinic acetylcholine receptor agonist PNU-282987 ameliorates sepsis-induced acute kidney injury through CD4⁺CD25⁺ regulatory T cells in rats［J］. Bosn J Basic Med Sci, 2022, 22(6):882-893.
［11］ Baris E, Simsek O, Arici M A, et al. Choline and citicoline ameliorate oxidative stress in acute kidney injury in rats［J］. Bratisl Lek Listy, 2023, 124(1):47-52.
［12］ Chatterjee P K, Yeboah M M, Solanki M H, et al. Activation of the cholinergic anti-inflammatory pathway by GTS-21 attenuates cisplatin-induced acute kidney injury in mice［J］. PLoS One, 2017, 12(11):e0188797.
［13］ Inoue T, Abe C, Sung S S, et al. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes［J］. J Clin Invest, 2016, 126(5):1939-1952.
［14］ Keever K R, Yakubenko V P, Hoover D B. Neuroimmune nexus in the pathophysiology and therapy of inflammatory disorders: role of α7 nicotinic acetylcholine receptors［J］. Pharmacol Res, 2023, 191:106758.
［15］ Ren C, Yao R Q, Zhang H, et al. Sepsis-associated encephalopathy: a vicious cycle of immunosuppression［J］. J Neuroinflammation, 2020, 17(1):14.
［16］ Kanashiro A, Sônego F, Ferreira R G, et al. Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis［J］. Pharmacol Res, 2017, 117:1-8.
［17］ Goggins E, Mitani S, Tanaka S. Clinical perspectives on vagus nerve stimulation: present and future［J］. Clin Sci (Lond), 2022, 136(9):695-709.

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