电刺激抗胃食管反流的作用及其相关神经通路的初步探讨*

杜植鹏#王斌&张伟刘晟宋鑫仇明&

第二军医大学附属长征医院普外三科(200003)

背景：局部电刺激下食管括约肌(LES)作为治疗胃食管反流病的新理念正处于起步阶段。目的：探索局部电刺激的理想参数，并初步探讨抑制LES收缩的局部神经反射通路。方法：构建抗胃食管反流的电刺激活体动物模型。观察胃食管反流量变化，探索电刺激抗胃食管反流的理想参数。在理想参数刺激下，分别加入不同药物干预，观察对胃食管反流量的影响。结果：频率10 Hz和脉冲0.4 ms时，电压10 V或15 V的胃食管反流量明显减少(P<0.001)；电压10 V和脉冲0.4 ms时，频率10 Hz的胃食管反流量明显减少(P<0.001)；电压10 V和频率10 Hz 时，脉冲0.4 ms的胃食管反流量显著降低(P<0.001)。食管壁局部浸润筒箭毒碱或辣椒素可显著提高胃食管反流量(P<0.05)；给予NK1受体阻断剂L-732,138或NO合酶抑制剂L-NAME后，胃食管反流量显著减少(P<0.05)。结论：考虑到电能对组织的损伤，理想电刺激参数为电压10 V、频率10 Hz和脉冲0.4 ms。食管壁内TRPV-1阳性的初级传入速激肽类神经元与肌间氮能神经元组成的局部反射通路可削弱电刺激诱发的LES收缩。

关键词胃食管反流病；电刺激；食管括约肌，下段；反射通路；辣椒素

Effect of Electrical Stimulation on Anti-reflux of Gastroesophageal Junction and Preliminary Exploration of Related Neural Pathway

DUZhipeng,WANGBin,ZHANGWei,LIUSheng,SONGXin,QIUMing.DepartmentofGeneralSurgery,ChangzhengHospital,theSecondMilitaryMedicalUniversity,Shanghai(200003)

Co-correspondence to: WANG Bin, Email: wangbin12048@163.com; QIU Ming, Email: qium127@sina.com

Background: As a new concept of treatment for gastroesophageal reflux disease (GERD), local electrical stimulation on lower esophageal sphincter (LES) is still in a preliminary stage. Aims: To explore the ideal local electrical stimulation parameters for LES contraction and the local neural reflex path that inhibits LES contraction. Methods: Anti-gastroesophageal reflux model with electrical stimulationinvivowas established. The changes of gastroesophageal reflux were observed to explore the ideal electrical stimulation parameters for LES contraction. Effects of different drugs on gastroesophageal reflux in condition with ideal electrical stimulation parameters were observed. Results: When frequency was 10 Hz and pulse was 0.4 ms, gastroesophageal reflux in voltage 10 V or 15 V groups was significantly decreased (P<0.001). When voltage was 10 V and pulse was 0.4 ms, gastroesophageal reflux in frequency 10 Hz group was significantly decreased (P<0.001). When voltage was 10 V and frequency was 10 Hz, gastroesophageal reflux in pulse 0.4 ms group was significantly decreased (P<0.001). Local infiltration of tubocurarine or capsaicin on LES could significantly increase gastroesophageal reflux (P<0.05). The administration of NK1 receptor blocker L-732,138 or NO synthase inhibitor L-NAME could significantly decrease gastroesophageal reflux (P<0.05). Conclusions: In view of the injury of electrical energy on tissue, the ideal electrical stimulation parameters are voltage of 10 V, frequency of 10 Hz and pulse of 0.4 ms. Local neural reflex path consisted of primary TRPV-1-positive tachykininergic neurons and nitrergic neurons in the muscle layer of esophagus could inhibit LES contraction evoked by electrical stimulation

Key wordsGastroesophageal Reflux Disease;Electric Stimulation;Esophageal Sphincter, Lower;

Reflex Path;Capsaicin

下食管括约肌(lower esophageal sphincter, LES)松弛是胃食管反流病(gastroesophageal reflux disease, GERD)的重要发病机制之一[1]。针对这一病因，目前最常用的抗反流术式为腹腔镜下胃底折叠术，抗反流效果较好，但术后可发生严重的并发症如吞咽困难、上腹部饱胀感、打嗝困难等。最近有学者提出新的治疗理念，即对LES行局部电刺激迷走神经末梢释放乙酰胆碱，引起括约肌收缩，提高LES压力(LES pressure, LESP)，进而加强胃食管的抗反流屏障功能[2]。该方法符合生理解剖特点，强度可调控，同时具有手术时间短、不会影响术后正常吞咽功能的优势。但这种治疗理念目前仍处于起步阶段，引起LES收缩的理想参数(频率、电流、脉冲、持续时间等)仍鲜有文献报道。有研究发现，在GERD发病机制中，LES松弛可能与抑制性神经递质如一氧化氮(nitric oxide, NO)、血管活性肽、神经肽等有关，这些神经递质与乙酰胆碱共同作用于食管运动终板，拮抗乙酰胆碱的作用[3]。……