Mercer D W, Ritchie W P, Dempsey D T
Reichle Research Laboratory, Department of Surgery, Temple University Hospital, Philadelphia, Pa.
Surgery. 1994 Feb;115(2):156-63.
Sensory neurons have been proposed to play a critical role in the protection of the gastric mucosa from a variety of necrotizing agents. The purposes of this study were (1) to investigate the effect of topical capsaicin, a sensory neuron stimulant, on the gastric mucosal injury caused by the topical application of low concentrations of bile acid and (2) to determine whether local neuronal blockade with topical lidocaine or cyclooxygenase blockade with systemic indomethacin has any effect during pretreatment with capsaicin.
Before injury with topical 5 mmol/L acidified taurocholate (pH 1.2) rat stomachs were pretreated with either vehicle or capsaicin (160 mmol/L), both with and without prior administration of either lidocaine (1%) or indomethacin (5 mg/kg subcutaneously). Injury was assessed by measuring net transmucosal ion fluxes, the appearance of deoxyribonucleic acid into the gastric lumen, and gross and histologic injury scores.
Pretreatment with topical capsaicin significantly (p < 0.05) decreased bile acid-induced net luminal ion fluxes and luminal deoxyribonucleic acid accumulation, an effect blocked by both lidocaine and indomethacin.
Thus both local neuronal blockade and cyclooxygenase inhibition block the protective effect of capsaicin, findings corroborated by gross and histologic injury analysis. This study suggests that sensory neurons may mediate gastric mucosal protection from bile acid injury by increasing synthesis of endogenous prostaglandins.
感觉神经元被认为在保护胃黏膜免受多种坏死因子的侵害中起关键作用。本研究的目的是：（1）研究局部应用辣椒素（一种感觉神经元刺激剂）对局部应用低浓度胆汁酸引起的胃黏膜损伤的影响；（2）确定局部应用利多卡因进行神经元阻滞或全身应用吲哚美辛进行环氧化酶阻滞在辣椒素预处理期间是否有任何作用。
在用局部5 mmol/L酸化牛磺胆酸盐（pH 1.2）造成损伤之前，用赋形剂或辣椒素（160 mmol/L）对大鼠胃进行预处理，同时给予或不给予利多卡因（1%）或吲哚美辛（5 mg/kg皮下注射）。通过测量净跨黏膜离子通量、胃腔内脱氧核糖核酸的出现以及大体和组织学损伤评分来评估损伤情况。
局部应用辣椒素预处理显著（p < 0.05）降低了胆汁酸诱导的腔内净离子通量和腔内脱氧核糖核酸积累，利多卡因和吲哚美辛均能阻断这一效应。
因此，局部神经元阻滞和环氧化酶抑制均能阻断辣椒素的保护作用，大体和组织学损伤分析证实了这一发现。本研究表明，感觉神经元可能通过增加内源性前列腺素的合成来介导胃黏膜免受胆汁酸损伤的保护作用。
