Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury
Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury
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DOI：
10.1172/jci200112218
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发表时间：
2001-12-01
影响因子：
15.9
通讯作者：
Kaunitz, JD
中科院分区：
文献类型：
--
作者：
Akiba, Y;Furukawa, O;Kaunitz, JD
从上皮细胞分泌碳酸氢盐被认为是保护十二指肠粘膜免受酸相关损伤的主要机制。与此观点相反的是，十二指肠碳酸氢盐分泌受损的囊性纤维化患者反而不会发生十二指肠溃疡。因此，我们假设上皮细胞胞内pH调节，而不是分泌细胞外碳酸氢盐，是保护十二指肠上皮细胞免受酸化和损伤的主要手段。使用一种新的体内显微镜方法，我们已经测量了碳酸氢盐的分泌和上皮细胞内pH值（pH（i）），我们已经遵循细胞损伤的阴离子转运抑制剂DIDS和Cl-通道抑制剂，5-硝基-2-（3-苯基丙基氨基）苯甲酸（NPPB）的存在下。DIDS和NPPB消除了腔内酸灌注后十二指肠碳酸氢盐分泌的增加。DIDS降低基础pHi，而NPPB增加pHi; DIDS在酸挑战期间进一步降低pHi，并消除酸挑战后观察到的超过基线的pHi过冲，而NPPB减弱了pHi的下降并夸大了过冲。最后，酸诱导的上皮损伤由DIDS增强，由NPPB降低。结果支持细胞内碳酸氢盐在保护十二指肠上皮细胞免受管腔胃酸的作用。
Secretion of bicarbonate from epithelial cells is considered to be the primary mechanism by which the duodenal mucosa is protected from acid-related injury. Against this view is the Finding that patients with cystic fibrosis, who have impaired duodenal bicarbonate secretion, are paradoxically protected from developing duodenal ulcers. Therefore, we hypothesized that epithelial cell intracellular pH regulation, rather than secreted extracellular bicarbonate, was the principal means by which duodenal epithelial cells are protected from acidification and injury. Using a novel in vivo microscopic method, we have measured bicarbonate secretion and epithelial cell intracellular pH (pH(i)), and we have followed cell injury in the presence of the anion transport inhibitor DIDS and the Cl-channel inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). DIDS and NPPB abolished the increase of duodenal bicarbonate secretion following luminal acid perfusion. DIDS decreased basal pHi, whereas NPPB increased pHi; DIDS further decreased pHi during acid challenge and abolished the pHi overshoot over baseline observed after acid challenge, whereas NPPB attenuated the fall of pHi and exaggerated the overshoot. Finally, acid-induced epithelial injury was enhanced by DIDS and decreased by NPPB. The results support the role of intracellular bicarbonate in the protection of duodenal epithelial cells from luminal gastric acid.