机械刺激诱导的远端结肠黏膜离子转运在腹泻型肠易激综合征大鼠模型中的变化

Alteration of mechanical stimulus-induced ions transport of distal colon in diarrhea predominant irritable bowel syndrome rat model

目的探讨在腹泻型肠易激综合征(D-IBS)大鼠中,机械刺激诱导的远端结肠黏膜离子转运是否发生改变。方法将Sprague-Dawley大鼠分为对照组和模型组,采用孤养+慢性非预见刺激的方法制备D-IBS大鼠模型,通过排便和蔗糖偏嗜度来检测D-IBS大鼠模型,采用短路电流技术结合去除溶液中阴离子和运用各种阻断剂的方法,观察机械刺激诱导的远端结肠黏膜离子转运。结果同对照组比较,模型组大鼠的排便数量显著增加,蔗糖偏嗜度显著降低,差异均有统计学意义(P<0.05)。2组大鼠结肠黏膜的基础电生理特性无显著差异(P>0.05)。机械刺激引起对照组和模型组大鼠结肠黏膜的短路电流均显著增加,但是模型组中增加的短路电流,显著高于对照组,差异有统计学意义(P<0.05)。去除溶液中的HCO3-并不能改变2组的短路电流,但是去除溶液中的Cl-均显著降低2组的短路电流,差异有统计学意义(P<0.001)。运用Ca2+激活的Cl-通道(CaCC)阻断剂4,4'-二异硫氰酰芪-二苯乙烯-2,2二磺酸二钠盐(DIDS)并不能改变2组的短路电流,但是运用囊性纤维变性跨膜电导调节器(CFTR)的抑制剂CFTR(inh)-172或Na+-K+-2Cl-共转运体(NKCC)的阻断剂bumetanide均显著降低2组的短路电流,差异有统计学意义(P<0.001)。结论在D-IBS大鼠模型中,机械刺激诱导的远端结肠黏膜Cl-分泌增加可能是D-IBS大鼠产生腹泻的原因之一。

Objective To investigate whether the mechanical stimulus-induced ions transport of distal colon of rats with diarrhea predominant irritable bowel syndrome（D-IBS） is altered. Methods The Sprague-Dawley rats were divided into control group and model group. The rats were exposed to individual housing combined with additional chronic unpredictable stress to induce D-IBS. The D-IBS model was tested by feces granules counting and sucrose consumption test. The mechanical stimu- lus-induced ions transport of distal colon were investigated using short circuit current technique combined with removal extracellular anions and application of different blockers. Results The amount of feces granules was increased and sucrose con- sumption was decreased in model group compared with control group（ P 〈 0.05 ）. There was no significant difference in electro-physiological properties between control group and model group（ P 〉 0.05 ）. The mechanical stimulus-induced short-circuit cur- rent in model group was statistically higher than that in control group（ P 〈 0.05 ）. The mechanical stimulus-induced short-circuit current in both control group and model group were reduced significantly by removal of extracellular Cl- （P 〈 0.001 ） but not by HCO3 -. The application of 4,4 ＇-diisothiocyanato-stilbenc-2,2＇-disulfonic acid （ DIDS ）, a Ca2 ＋ -activated Cl - channel blocker, didn＇t alter the short-circuit current induced by mechanical stimulus in both groups. However, addition of CFTR（inh） - 172 ,the inhibitor of cystic fibrosis transmembrane conductance regulator, or bumetanide, a blocker of Na ＋ -K ~ -2C1- cotransporter reduced the mechanical stimulus-induced short-circuit current in control group and model group significantly （P 〈 0. 001 ）. Conclusion The mechanical stimulus can induce the secretion of Cl- in distal colon of model rats, which is a possible mechanism responsible for the diarrhea of D-IBS rats.