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[目的]通过观察疏肝健脾方对腹泻型肠易激综合征(IBS-D)模型大鼠多巴胺信号通路结肠黏膜离子转运的影响,旨在探讨疏肝健脾方对IBS-D的疗效机制。[方法]将体质量180~220g雄性SD大鼠随机分为正常对照组、IBS-D模型组和疏肝健脾方治疗组,除正常对照组外,其他2组进行造模;采用体外短路电流测量技术测定各组大鼠结肠黏膜的短路电流变化。[结果]3组大鼠在基础电流、基础电压及跨上皮电阻三项电参数方面比较均差异无统计学意义(P>0.05);多巴胺(DA)引起的最大短路电流下降值(△Isc),疏肝健脾方治疗组较IBS-D模型组明显减小(P<0.05);将Cl-,HCO3-,Cl-/HCO3-从K-HS液中替代后,3组大鼠的△Isc均减小但3组间△Isc比较差异无统计学意义(P>0.05);分别采用非选择性Cl-通道阻断剂glibenclamide、DPC阻断顶膜侧Cl-转运后,3组大鼠的△Isc均减小但3组间△Isc比较差异无统计学意义(P>0.05);采用上皮Na+通道阻断剂Amiloride阻断顶膜侧的Na+转运后、非选择性K+通道阻断剂Ba2+阻断顶膜侧K+转运后,3组大鼠的△Isc均基本不受影响,疏肝健脾方治疗组较IBS-D模型组明显减小(P<0.05);采用抑制剂Bumitanide抑制黏膜基底侧Na+-K+-2Cl-共转运体的离子、抑制剂SITS抑制黏膜基底侧Cl-/HCO3-转运后,3组大鼠的△Isc均减小但3组间△Isc比较差异无统计学意义(P>0.05)。[结论]疏肝健脾方对IBS-D模型大鼠治疗作用的发挥与其对大鼠结肠黏膜多巴胺通路相关的Cl-及HCO3-转运的调节作用有关,这一过程主要由结肠黏膜顶膜侧Cl-通道,基底膜侧阴离子交换体及Na+-K+-2Cl-共转运体等膜通道蛋白共同介导。
[Objective] To observe the effect of Shugan Jianpi Recipe on the ion transport of colonic mucosa in dopaminergic signaling pathway in diarrhea-predominant Irritable Bowel Syndrome (IBS-D) model rats and to explore the effect of Shugan Jianpi Recipe on IBS-D mechanism. [Methods] Male Sprague-Dawley rats weighing 180-220 g were randomly divided into normal control group, IBS-D model group and Shuganjianpi Decoction group. Except for the normal control group, the other two groups were modeled; short-circuit Current measurement technique was used to measure the short-circuit current of colonic mucosa of rats in each group. [Results] There was no significant difference in the three parameters of basal current, basal voltage and trans-epithelial resistance between the three groups (P> 0.05), but the decrease of maximum short circuit current (△ Isc) induced by dopamine , And Shuganjianpi Decoction treatment group was significantly lower than that of IBS-D model group (P <0.05). After Cl-, HCO3-, Cl- / HCO3- substitution from K-HS solution, △ Isc were decreased but there was no significant difference between the three groups (P> 0.05). After the Cl-transport on the apical membrane was blocked by glibenclamide, a non-selective Cl-channel blocker, (P> 0.05). Amiloride, a blocker of epithelial Na + channel, blocked Na + transport on the apical membrane and non-selective K + channel blockers Ba2 + blocking the apical membrane K + transport, △ Isc of three groups of rats were basically not affected, Shuganjianpi Decoction group than the IBS-D model group was significantly reduced (P <0.05); inhibitor Bumitanide inhibition Mucosal basal side of the Na + -K + -2Cl-cotransporter ion, inhibitor SITS inhibit mucosal basal side Cl- / HCO3-transport, △ Isc three groups were reduced but the difference between the three groups △ Isc no statistics Significance (P> 0.05) . [Conclusion] The effect of Shuganjianpi Decoction on IBS-D model rats is related to the regulation of Cl- and HCO3- transporters related to dopamine pathway in colonic mucosa in rats. This process mainly consists of the apical membrane of colonic mucosa Cl-channel, basement membrane anion exchanger and Na + -K + -2Cl-co-transporters and other membrane channel proteins co-mediated.