Objective: To study the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on gastric sensitivity and motility in rats with functional dyspepsia (FD), so as to explore its underlying mechanism in improving FD.
Methods: A total of 48 young SD rats were randomly divided into control (n=10), model (n=9), taVNS (n=9), subdiaphragmatic vagus nerve stimulation (SDVNS, n=9) and sham SDVNS (n=7) groups. The FD model was established by gavage of 0.1% iodoa-cetamide+2% glucose, once daily for 6 days. Rats in the taVNS group received taVNS (0.5 mA) of optopoint "Heart" and "Stomach" for 30 min, once daily for 14 days, while rats in the SDVNS group received subdiaphragmatic vagus nerve stimulation through the implanted electrode, and those of the sham SDVNS group received only application of the same electrodes without electrical stimulation. Electromyogram (EMG) of the cervical trapezius muscle (reflecting gastric sensitivity) was recorded before and after intragastric expansion via an air ballon and the gastric emptying rate was calculated for assessing the gastric motility. The contents of acetylcholine (ACh), nicotinic acetylcholine receptor α7 subunit (α7nAChR), interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the duodenum tissue were detected by enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) p65 in the duodenum tissue was determined by Western blot.
Results: In comparison with the control group, the EMG change rate at intragastric pressure levels of 40, 60 and 80 mm Hg, expression of NF-κB p65 protein, and contents of IL-6, IL-1β and TNF-α were significantly increased (P<0.05,P<0.01, P<0.001), while the gastric emptying rate, ACh and α7nAChR contents considerably decreased (P<0.05, P<0.001) in the model group. After interventions, the EMG change rate, contents of IL-6, IL-1β and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.05, P<0.01, P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.05, P<0.001) in both taVNS and SDVNS groups relevant to the model group. In comparison with the sham SDVNS group, the EMG change rate, contents of IL-6, IL-1β and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.01, P<0.05,P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.01, P<0.001) in the both SDVNS and taVNS groups.
Conclusion: taVNS can reduce gastric sensitivity and promote gastric emptying in FD model rats, which may be closely related to its functions in up-regulating ACh and α7nAChR contents and inhibiting the activation of NF-κB p65 signaling in the duodenum.
目的：观察经皮耳穴迷走神经刺激(taVNS)对功能性消化不良(FD)模型大鼠胃敏感性及胃动力的影响，探讨其作用机制。方法：选用5日龄SD大鼠，以灌服碘乙酰胺法复制FD模型。大鼠随机分为空白组、模型组、taVNS组、膈下迷走神经刺激组、膈下迷走神经假刺激组。taVNS组大鼠予以taVNS，膈下迷走神经刺激组通过植入的电极给予膈下迷走神经刺激，膈下迷走神经假刺激组仅植入电极而不予刺激，模型组不予刺激。以上干预均为30 min/次，1次/d，连续干预14 d。分别于干预前后检测各组大鼠颈斜方肌肌电(EMG)变化率，于干预后测定胃排空率，ELISA法检测十二指肠组织乙酰胆碱(ACh)、烟碱型乙酰胆碱N型受体α7亚单位(α7nAChR)、白细胞介素(IL)-6、IL-1β及肿瘤坏死因子-α(TNF-α)的含量，Western blot法测定十二指肠组织中核因子-κB(NF-κB)p65的表达。结果：与空白组比较，模型组大鼠在40、60、80 mm Hg压力时颈斜方肌EMG变化率、十二脂肠组织NF-κB p65表达及IL-6、IL-1β、TNF-α含量均升高(P<0.05,P<0.01，P<0.001)，胃排空率、十二脂肠组织ACh及α7nAChR含量均降低(P<0.05，P<0.001)。与模型组比较，taVNS组、膈下迷走神经刺激组大鼠颈斜方肌EMG变化率、十二脂肠组织NF-κB p65表达及IL-6、IL-1β、TNF-α含量均降低(P<0.05，P<0.01，P<0.001)，胃排空率、十二脂肠组织ACh及α7nAChR含量均升高(P<0.05，P<0.001)。与膈下迷走神经假刺激组比较，膈下迷走神经刺激组和taVNS组大鼠颈斜方肌EMG变化率、十二脂肠组织NF-κB p65表达及IL-6、IL-1β、TNF-α含量均降低(P<0.01，P<0.05，P<0.001)，胃排空率、十二脂肠组织ACh及α7nAChR含量升高(P<0.01，P<0.001)。结论：taVNS可降低FD大鼠胃敏感性，促进胃排空，其作用机制可能与促进十二指肠ACh及α7nAChR表达进而抑制NF-κB信号通路激活密切相关。.
Keywords: Acetylcholine; Functional dyspepsia; Gastric motility; Gastric sensitivity; Nicotinic acetylcholine receptor α7 subunit; Subphrenic vagus nerve stimulation; Transcutaneous auricular vagus nerve stimulation.