Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Acta Physiol (Oxf). 2014 Jun;211(2):421-33. doi: 10.1111/apha.12301.
Biliary tract obstruction is a common clinical lesion. However, the effect of biliary tract obstruction on intestinal secretion is poorly understood. In this study, we made an investigation on intestinal HCO3 (-) and Cl(-) secretions in an experimental model of murine biliary duct ligation.
Murine intestinal mucosal HCO3 (-) and Cl(-) secretions were examined in vitro in Ussing chambers by pH-stat and short-circuit current (Isc ) techniques. The mRNA and protein expressions of the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na(+) -K(+) -2Cl(-) cotransporter (NKCC1) were analysed by real-time PCR, western blot and immunohistochemistry.
Basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with common biliary duct ligation were markedly elevated, compared with controls (P < 0.05 and P < 0.01). Further experiments showed that basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with external bile drainage were also markedly elevated. CFTRinh -172 inhibited forskolin-stimulated HCO3 (-) and Cl(-) secretions. The mRNA and protein expression levels of CFTR and NKCC1 in the intestinal mucosa with both biliary duct ligation and external bile drainage were markedly higher than those in controls (P < 0.001). Bile acid administration restored the changes in function and expression of CFTR and NKCC1 in the intestinal mucosa.
Bile deficiency in the intestine up-regulates the expressions of intestinal mucosal CFTR and NKCC1 and enhances intestinal mucosal HCO3 (-) and Cl(-) secretion capacity, which contributes to the understanding of intestinal physiological function for patients with biliary duct obstruction.
胆道梗阻是一种常见的临床病变。然而，胆道梗阻对肠道分泌的影响还不太清楚。在本研究中，我们在胆管结扎的实验模型中研究了肠道 HCO3（-）和 Cl（-）的分泌。
通过 pH -stat 和短路电流（Isc）技术，在 Ussing 室中检测了体外鼠肠黏膜 HCO3（-）和 Cl（-）的分泌。通过实时 PCR、western blot 和免疫组织化学分析囊性纤维化跨膜电导调节剂（CFTR）和 Na（+）-K（+）-2Cl（-）共转运蛋白（NKCC1）的 mRNA 和蛋白表达。
与对照组相比，普通胆管结扎小鼠的基础 Cl（-）分泌和福司可林刺激的十二指肠和空肠黏膜 HCO3（-）和 Cl（-）分泌明显增加（P < 0.05 和 P < 0.01）。进一步的实验表明，外部胆汁引流的小鼠的基础 Cl（-）分泌和福司可林刺激的十二指肠和空肠黏膜 HCO3（-）和 Cl（-）分泌也明显增加。CFTRinh-172 抑制福司可林刺激的 HCO3（-）和 Cl（-）分泌。胆管结扎和外部胆汁引流的肠黏膜 CFTR 和 NKCC1 的 mRNA 和蛋白表达水平明显高于对照组（P < 0.001）。胆汁酸给药恢复了肠黏膜 CFTR 和 NKCC1 功能和表达的变化。
肠道胆汁缺乏可上调肠黏膜 CFTR 和 NKCC1 的表达，增强肠黏膜 HCO3（-）和 Cl（-）的分泌能力，有助于了解胆道梗阻患者的肠道生理功能。
