关键词: 脓毒症, 急性肾损伤, 迷走神经刺激, 胆碱能抗炎通路, α7烟碱型乙酰胆碱受体

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