TRPV1和NaV1.8在食管高敏感中的作用和机制研究
| 作 者：吴白馨, 次仁玉珍, 彭帅, 吴祖楠, 张毓玲, 余晓云, 沈磊 |
| 单 位：武汉大学人民医院 |
| 基金项目：国家自然科学基金 |
| 摘 要： |
| 背景：食管高敏感是胃食管反流病（GERD）患者烧心等症状产生的重要原因。瞬时受体电位香草酸亚型1（TRPV1）和电压门控钠离子通道1.8（NaV1.8）可能在食管高敏感的调控中发挥重要作用。目的：检测TRPV1、NaV1.8在GERD动物模型食管和迷走神经感觉神经元中的表达，探究其在食管高敏感中的作用。方法：12只雄性豚鼠随机分为对照组和GERD组，后者通过饮用盐酸胃蛋白酶溶液建立GERD模型。通过观察动物体质量变化、食管炎症组织学评分和炎症细胞因子表达验证造模成功与否。通过分析心率变异性（HRV）明确动物是否处于内脏高敏感状态。以免疫荧光法、qRT-PCR和蛋白质印迹法检测食管、迷走神经结状神经节和颈静脉神经节中的TRPV1、NaV1.8表达、分布和共表达情况。结果：GERD组食管炎症组织学评分显著高于对照组（0.85±0.43对0.22±0.45），促炎细胞因子表达增高，抗炎细胞因子表达降低，体质量增长缓慢（P均<0.05）。造模前两组HRV指标低频/高频（LF/HF）比值无明显差异（P>0.05），造模后GERD组LF/HF比值显著增高（P<0.05）。GERD组食管黏膜上皮和颈静脉神经节TRPV1、NaV1.8表达和共表达均显著上调（P均<0.05），结状神经节中两者表达无明显变化（P均>0.05）。结论：在食管酸暴露情况下，食管黏膜上皮TRPV1、NaV1.8表达增高，迷走神经颈静脉神经节中两者表达亦显著上调，促进迷走神经通路伤害性信号的传递，最终导致食管高敏感发生。 |
| 关键词：胃食管反流病；食管高敏感；TRPV1；NaV1.8；结状神经节；颈静脉神经节 |
Role and Mechanism of TRPV1 and NaV1.8 in Esophageal Hypersensitivity
| Author's Name: |
| Institution: |
| Abstract: |
| Background: Hypersensitivity of esophagus is an important cause of heartburn and other symptoms in patients with gastroesophageal reflux disease (GERD). It has been revealed that transient receptor potential vanilloid type 1 (TRPV1) and voltage-gated sodium channel NaV1.8 might contribute to the regulation of esophageal hypersensitivity. Aims: To explore the expression levels of TRPV1 and NaV1.8 in esophagus and vagal sensory neurons in GERD animal model and their roles in mediating esophageal hypersensitivity. Methods: Twelve male guinea pigs were randomly allocated into control group and GERD group. Model of GERD was established by drinking hydrochloric-pepsinogen acid water and verified by body weight monitoring, esophageal inflammatory histological scoring and measurements of pro- and anti-inflammatory cytokines. Visceral hypersensitivity was determined by heart rate variability (HRV) analysis. Expressions, distribution, and co-expression of TRPV1 and NaV1.8 in esophagus and vagal nodose/jugular ganglia were quantified by immunofluorescence, qRT-PCR and Western blotting. Results: Compared with the control group, score of esophageal inflammatory histology in GERD group was increased (0.85±0.43 vs. 0.22±0.45), accompanied by elevated proinflammatory cytokine expressions and reduced antiinflammatory cytokine expression (all P<0.05). The weight gain was also slower in GERD group than in control group (P<0.05). As an indicator of HRV analysis, the low frequency to high frequency (LF/HF) ratio had no significant difference between GERD group and control group before model construction (P>0.05), but increased significantly in GERD group after modeling (P<0.05). In GERD group, expressions and co-expression of TRPV1 and NaV1.8 were up-regulated in esophageal mucosal epithelium and jugular ganglion (all P<0.05), but not changed in nodose ganglion (all P>0.05). Conclusions: In the acid-exposed esophagus, expressions of TRPV1 and NaV1.8 were up-regulated in esophageal mucosal epithelium and vagal jugular ganglion, thus promoting the nociceptive transmission in vagus nerve pathway, and ultimately resulting in esophageal hypersensitivity. |
| Keywords: Gastroesophageal Reflux Disease; Esophageal Hypersensitivity; TRPV1; NaV1.8; Nodose Ganglion; Jugular Ganglion |
| 投稿时间：2023-10-18 |
|
|
|
查看pdf文件
|
|
