| 摘要: |
| [目的] 研究半夏调中颗粒对非糜烂性反流病（NERD）内脏高敏感（VH）模型大鼠食管及背根神经节（DRG）神经生长因子（NGF）/原肌球蛋白受体激酶 A（TrkA）通路的影响，探讨其疗效机制。[方法] 将 36 只 SD 大鼠随机分为空白组、模型组、半夏调中颗粒组（BXTZ 组）、奥美拉唑组、TrkA 抑制剂（GW 441756）组及半夏调中颗粒+TrkA 激动剂（BXTZ+GA-amide）组，每组 6 只，除空白组外，各组均建立内脏高敏感 NERD 大鼠模型，14 d 后观察各组机械缩足反射阈值（MWT）、垂直及水平得分，检测各组血清 NGF、蛋白酶激活受体 2（PAR-2）、瞬时受体电位香草酸亚型 1（TRPV1）表达水平，各组食管及背根神经节 NGF、TrkA、PAR-2、TRPV1 蛋白水平，记录食管肥大细胞（MC）计数及密度，免疫荧光双标法检测各组食管 NGF、TrkA 荧光强度。[结果] 与空白组相比，模型组 MWT、水平及垂直得分均降低（P<0.05），血清 NGF、PAR-2、TRPV1 水平、食管及背根神经节 NGF、TrkA、PAR-2、TRPV1 蛋白水平、食管 MC 计数及密度、NGF、TrkA 荧光强度均升高（P<0.05）。与模型组相比，BXTZ 组 MWT、水平及垂直得分均升高（P<0.05），血清 NGF、PAR-2、TRPV1 水平、食管及背根神经节 NGF、TrkA、PAR-2、TRPV1 蛋白水平、食管 MC 计数及密度、NGF、TrkA 荧光强度均降低（P<0.05）。组间比较，BXTZ 组较奥美拉唑组 MWT、水平及垂直得分升高均更显著（P<0.05），较 GW 441756 组水平及垂直得分升高更显著（P<0.05）；BXTZ 组较奥美拉唑组血清 NGF、PAR-2、TRPV1水平、食管及背根神经节 NGF、TrkA、PAR-2、TRPV1 蛋白水平、食管 MC 计数及密度、NGF、TrkA 荧光强度均降低（P<0.05），较 GW 441756 组血清、食管及背根神经节 NGF、PAR-2、TRPV1 水平、食管 MC 密度降低更显著（P<0.05）。[结论] 半夏调中颗粒能够调控 NGF/TrkA 通路，抑制 MC 活化脱颗粒，减轻食管 VH，发挥治疗 NERD 的作用。 |
| 关键词: 非糜烂性反流病 半夏调中颗粒 内脏高敏感 神经生长因子 原肌球蛋白受体激酶A |
| DOI：10.11656/j.issn.1672-1519.2026.10.11 |
| 分类号:R285.5 |
| 基金项目:湖北省自然科学基金项目（2025AFB910）；老年脑健康中医药防护技术与新产品研发教育部工程研究中心开放基金资助项目；湖北省时珍人才工程科研项目（鄂卫函〔2024〕256号）。 |
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| Study on the mechanism of Banxia Tiaozhong Granules in regulating the NGF/TrkA pathway to improve visceral hypersensitivity in the treatment of non-erosive reflux disease |
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ZHANG Shu1,2, SHI Zhaohong1, LI Shuangyi2, FENG Yunxia1, SHU Lei1
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1.Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430022, China;2.Hubei University of Chinese Medicine, Wuhan 430065, China
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| Abstract: |
| [Objective] To investigate the effect of Banxia Tiaozhong Granules（BXTZ）on the NGF/TrkA pathway in the esophagus and dorsal root ganglion（DRG）of rats with visceral hypersensitivity（VH）in non-erosive reflux disease（NERD），and to explore its therapeutic mechanism. [Methods] The 36 Sprague-Dawley（SD）rats were randomly assigned to six groups（n=6 per group）：control， model，BXTZ，omeprazole，TrkA inhibitor（GW 441756），BXTZ+TrkA agonist（BXTZ+GA-amide）. Except for the control group，all other groups were subjected to the establishment of a rat model of NERD with VH. After 14 days，the mechanical withdrawal threshold （MWT），vertical and horizontal activity scores were measured. The levels of serum NGF，PAR-2，and TRPV1 were detected. The protein expressions of NGF，TrkA，PAR-2，and TRPV1 in the esophagus and DRG were determined. The count and density of mast cells （MC）in the esophagus were recorded. Double immunofluorescence staining was used to detect the fluorescence intensities of NGF and TrkA in the esophagus. [Results] Compared with the blank group，the MWT value，horizontal score，and vertical score in the model group were significantly decreased（P<0.05），while the serum levels of NGF，PAR-2，and TRPV1，the protein levels of NGF，TrkA，PAR-2， and TRPV1 in the esophagus and DRG，the count and density of MC in the esophagus，and the fluorescence intensities of NGF and TrkA（in the esophagus）were significantly increased（P<0.05）. Compared to the model group，the BXTZ group showed significantly increased MWT，vertical and horizontal activity scores（P<0.05），while the serum levels of NGF，PAR-2，and TRPV1，protein expressions of NGF，TrkA，PAR-2，and TRPV1 in the esophagus and DRG，count and density of esophageal MC，and fluorescence intensities of NGF and TrkA in the esophagus were significantly decreased（P<0.05）. Intergroup comparisons showed that the BXTZ group had more significant increases in MWT，vertical and horizontal activity scores than the omeprazole group（P<0.05），and more significant increases in vertical and horizontal activity scores than the GW 441756 group（P<0.05）. Additionally，the BXTZ group exhibited more significant decreases in serum，esophageal，and DRG levels of NGF，PAR-2，and TRPV1，as well as esophageal MC density，compared with the omeprazole group and GW 441756 group（P<0.05）. The fluorescence intensities of NGF and TrkA in the esophagus of the BXTZ group were also more significantly reduced than those in the omeprazole group（P<0.05）. [Conclusion] Banxia Tiaozhong Granules exerts a therapeutic effect on NERD by regulating the NGF/TrkA pathway，inhibiting MC activation and degranulation，and alleviating esophageal VH. |
| Key words: non-erosive reflux disease Banxia Tiaozhong Granule visceral hypersensitivity nerve growth factor tropomyosin receptor kinase A |
