Mercer D W, Milner R, O'Neill S, Ritchie W P, Dempsey D T
Reichle Research Laboratory, Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania 19140.
J Surg Res. 1991 Jun;50(6):602-8. doi: 10.1016/0022-4804(91)90049-r.
Leukotriene C4 and D4 are putative mediators of the severe gastric mucosal injury caused by a variety of topical irritants. The purpose of this present study was (1) to investigate the effect of pretreatment with topical leukotriene C4 and D4 on the more superficial injury caused by low concentrations of bile acid and (2) to determine the effect of leukotriene receptor blockade, alone and during leukotriene pretreatment, on this injury. Prior to injury with topical 5 mM acidified taurocholate (pH 1.2) rat stomachs were pretreated with either normal saline, leukotriene C4 or D4, SKF-104353 (a leukotriene receptor antagonist), SKF-104353/LTC4, or SKF-104353/LTD4. Injury was assessed by measuring hydrogen ion flux and DNA efflux, a marker of gastric mucosal cell exfoliation. Both LTC4 and LTD4 significantly increased bile acid-induced luminal hydrogen ion loss and DNA efflux. Leukotriene receptor blockade not only blocked this effect, but also significantly decreased the injury from bile acid alone. Thus, both LTC4 and LTD4 exacerbate the superficial gastric mucosal injury caused by physiologic concentrations of bile acids. Leukotriene receptor blockade with SKF-104353 completely blocks these effects and reduces injury from bile acid alone.
白三烯C4和D4被认为是由多种局部刺激物引起的严重胃黏膜损伤的介质。本研究的目的是：（1）研究局部应用白三烯C4和D4预处理对低浓度胆汁酸所致较浅表损伤的影响；（2）确定白三烯受体阻断剂单独应用及在白三烯预处理期间对该损伤的影响。在用局部5 mM酸化牛磺胆酸盐（pH 1.2）损伤大鼠胃之前，分别用生理盐水、白三烯C4或D4、SKF-104353（一种白三烯受体拮抗剂）、SKF-104353/白三烯C4或SKF-104353/白三烯D4对大鼠胃进行预处理。通过测量氢离子通量和DNA外排（胃黏膜细胞脱落的标志物）来评估损伤。白三烯C4和白三烯D4均显著增加胆汁酸诱导的管腔氢离子丢失和DNA外排。白三烯受体阻断不仅阻断了这种作用，而且还显著降低了单独由胆汁酸引起的损伤。因此，白三烯C4和白三烯D4均会加重生理浓度胆汁酸所致的浅表胃黏膜损伤。用SKF-104353阻断白三烯受体可完全阻断这些作用，并减少单独由胆汁酸引起的损伤。
