Stimulation of duodenal HCO3- secretion by hydrogen sulphide in rats: relation to prostaglandins, nitric oxide and sensory neurones
Stimulation of duodenal HCO3- secretion by hydrogen sulphide in rats: relation to prostaglandins, nitric oxide and sensory neurones
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DOI：
10.1111/j.1748-1716.2010.02152.x
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发表时间：
2011-01-01
影响因子：
6.3
通讯作者：
Takeuchi, K.
中科院分区：
文献类型：
--
作者：
Ise, F.;Takasuka, H.;Takeuchi, K.
目的：我们研究了硫化氢（H₂S）对大鼠十二指肠碳酸氢盐（HCO₃⁻）分泌的影响，并探讨了该反应所涉及的机制。
方法：动物禁食18小时，用乌拉坦麻醉。用生理盐水灌注十二指肠袢，采用pH-stat法在pH 7.0时测量HCO₃⁻分泌。以0.2 mL/min的速率用硫氢化钠（NaHS，H₂S供体：0.1 - 1 mM）灌注5分钟或用10 mM盐酸灌注10分钟。在给予NaHS或酸化之前，分别皮下注射吲哚美辛或L - NAME[一氧化氮（NO）合酶抑制剂]30分钟或3小时，而在30分钟前腹腔注射格列本脲（K - ATP通道阻滞剂）或炔丙基甘氨酸（胱硫醚 - γ - 裂解酶抑制剂）。
结果：黏膜用NaHS灌注呈剂量依赖性地增加HCO₃⁻分泌，这种作用被吲哚美辛和L - NAME以及感觉神经去传入显著减弱，但不被格列本脲减弱。NaHS灌注使黏膜前列腺素E₂（PGE₂）产生和NO的管腔释放均增加。黏膜酸化刺激HCO₃⁻分泌，同时PGE₂和NO产生增加，这些反应被炔丙基甘氨酸减轻。用炔丙基甘氨酸预处理会加重酸（100 mM盐酸处理4小时）诱导的十二指肠损伤。
结论：这些结果表明，H₂S增加大鼠十二指肠的HCO₃⁻分泌，这种作用部分由前列腺素（PG）和NO以及辣椒素敏感的传入神经元介导。推测内源性H₂S参与十二指肠中酸诱导的HCO₃⁻分泌的调节机制和黏膜保护。
Aim:We examined the effect of H2S on duodenal HCO3- secretion in rats and investigated the mechanism involved in this response.Methods:Animals were fasted for 18 h and anaesthetized with urethane. A duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH stat-method. The loop was perfused at a rate of 0.2 mL min-1 with NaHS (H2S donor: 0.1-1 mm) for 5 min or 10 mm HCl for 10 min. Indomethacin or l-NAME [nitric oxide (NO) synthase inhibitor) was given s.c. 30 min or 3 h, respectively, before NaHS or acidification, while glibenclamide (K-ATP channel blocker) or propargylglycine (cystathionine-g-lyase inhibitor) was given i.p. 30 min before.Results:Mucosal perfusion with NaHS dose dependently increased the HCO3- secretion, and this effect was significantly attenuated by indomethacin and l-NAME as well as by sensory deafferentation, but not by glibenclamide. Mucosal prostaglandin E-2 (PGE(2)) production and luminal release of NO were both increased by NaHS perfusion. Mucosal acidification stimulated HCO3- secretion concomitant with an increase in PGE(2) and NO production, and these responses were mitigated by propargylglycine. The duodenal damage induced by acid (100 mm HCl for 4 h) was aggravated by pre-treatment with propargylglycine.Conclusion:These results suggest that H2S increases HCO3- secretion in the rat duodenum, and that this action is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurones. It is assumed that endogenous H2S is involved in the regulatory mechanism of acid-induced HCO3- secretion and mucosal protection in the duodenum.