Han Juan, Wei Wei, Wang Hong-Cai, Zhang Tao, Wang Yu, Hou Li-Wei, Li Shao-Yuan, Zhang Jin-Ling, Rong Pei-Jing
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102.
Zhen Ci Yan Jiu. 2022 Jun 25;47(6):517-24. doi: 10.13702/j.1000-0607.20220111.
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.
A total of 48 young SD rats were randomly divided into control (=10), model (=9), taVNS (=9), subdiaphragmatic vagus nerve stimulation (SDVNS, =9) and sham SDVNS (=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.
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 (<0.05,<0.01, <0.001), while the gastric emptying rate, ACh and α7nAChR contents considerably decreased (<0.05, <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 (<0.05, <0.01, <0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (<0.05, <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 (<0.01, <0.05,<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (<0.01, <0.001) in the both SDVNS and taVNS groups.
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.
研究经皮耳迷走神经刺激(taVNS)对功能性消化不良(FD)大鼠胃敏感性和胃动力的影响,以探讨其改善FD的潜在机制。
将48只年轻SD大鼠随机分为对照组(=10)、模型组(=9)、taVNS组(=9)、膈下迷走神经刺激(SDVNS,=9)组和假SDVNS组(=7)。通过灌胃0.1%碘乙酰胺+2%葡萄糖建立FD模型,每天1次,共6天。taVNS组大鼠接受“心”和“胃”耳穴的taVNS(0.5 mA)刺激30分钟,每天1次,共14天;SDVNS组大鼠通过植入电极接受膈下迷走神经刺激,假SDVNS组大鼠仅应用相同电极但不进行电刺激。通过气钡囊进行胃扩张前后记录颈斜方肌肌电图(EMG)(反映胃敏感性),并计算胃排空率以评估胃动力。采用酶联免疫吸附测定(ELISA)法检测十二指肠组织中乙酰胆碱(ACh)、烟碱型乙酰胆碱受体α7亚基(α7nAChR)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的含量。采用蛋白质免疫印迹法检测十二指肠组织中核因子κB(NF-κB)p65的表达。
与对照组相比,模型组在胃内压为40、60和80 mmHg时的EMG变化率、NF-κB p65蛋白表达以及IL-6、IL-1β和TNF-α含量显著升高(<0.05,<0.01,<0.001),而胃排空率、ACh和α7nAChR含量显著降低(<0.05,<0.001)。干预后,与模型组相比,taVNS组和SDVNS组的EMG变化率、IL-6、IL-1β和TNF-α含量以及NF-κB p65表达显著降低(<0.05,<0.01,<0.001),胃排空率、ACh和α7nAChR含量明显升高(<0.05,<0.001)。与假SDVNS组相比,SDVNS组和taVNS组的EMG变化率、IL-6、IL-1β和TNF-α含量以及NF-κB p65表达显著降低(<0.01,<0.05,<0.001),胃排空率、ACh和α7nAChR含量明显升高(<0.01,<0.001)。
taVNS可降低FD模型大鼠的胃敏感性并促进胃排空,这可能与其上调十二指肠中ACh和α7nAChR含量以及抑制NF-κB p65信号通路激活的作用密切相关。