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膳食纤维和腔内压力对大鼠空肠原位吸收及上皮前扩散阻力(静止层)的影响。

Influence of dietary fiber and intraluminal pressure on absorption and pre-epithelial diffusion resistance (unstirred layer) in rat jejunum in situ.

作者信息

Holzheimer G, Winne D

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1986 Dec;334(4):514-24. doi: 10.1007/BF00569395.

Abstract

The appearance rates of antipyrine, benzoic acid, benzylamine, urea, and alpha-methyl-D-glucoside (MG) in jejunal venous blood of anesthetized rats were measured with and without dietary fibers methylcellulose, carboxymethylcellulose sodium, guaran, and sodium alginate in the luminal solution. Raising the concentration of methylcellulose from 0 to 17.5 g/l resulted in an exponential increase in the viscosity of the solution to 98 cSt, a linear decrease of the diffusion coefficient for antipyrine by 28%, and an increase in antipyrine absorption in the perfused jejunal segment by 23%. The simultaneous increase in intraluminal pressure and radius resulted in a linear relation between absorption rate and apparent mucosal surface area. Similar results were obtained by raising intraluminal pressure directly using a carbohydrate-free perfusion solution. In the perfused rat jejunum, the effect of increased pre-epithelial diffusion resistance (i.e. reduced diffusion coefficient and lengthened diffusion distance) induced by methylcellulose on absorption was overcome by the effect of the enlarged apparent mucosal surface area. Preperfusion of a substrate-free, guaran containing solution followed by perfusion with a guaran-free solution containing antipyrine and MG retarded the increase in the appearance rate of these substrates due to the additional viscous guaran layer left after preperfusion. Constant distension of the intestinal wall was achieved by injecting 0.5 ml of the solution into a closed jejunal segment. Addition of the carbohydrates to the injection solution (approx. 100 cSt viscosity) resulted in a 3% to 20% reduction in the diffusion coefficients and in the absorption of antipyrine, benzoic acid, and MG. Diffusion coefficients for urea and benzylamine were reduced by 5% to 12%; absorption varied in the range of the control (-22% to +43%). Model analysis revealed that, in the closed jejunal segment of the rat, the limiting step in the absorption process of antipyrine, benzoic acid, and MG was pre-epithelial diffusion resistance; the reduction of absorption, therefore, corresponded roughly to that of the diffusion coefficient. In the case of urea and benzylamine, pre-epithelial diffusion resistance was only 20% of the total permeation resistance: the influence of the polymers on absorption, therefore, was not always significant.

摘要

在管腔溶液中添加或不添加膳食纤维(甲基纤维素、羧甲基纤维素钠、瓜尔豆胶和海藻酸钠)的情况下,测定了麻醉大鼠空肠静脉血中安替比林、苯甲酸、苄胺、尿素和α-甲基-D-葡萄糖苷(MG)的出现率。将甲基纤维素的浓度从0提高到17.5 g/l,溶液粘度呈指数增加至98 cSt,安替比林的扩散系数线性降低28%,灌注空肠段中安替比林的吸收增加23%。管腔内压力和半径同时增加,导致吸收率与表观粘膜表面积之间呈线性关系。使用无碳水化合物灌注溶液直接提高管腔内压力也得到了类似结果。在灌注的大鼠空肠中,甲基纤维素引起的上皮前扩散阻力增加(即扩散系数降低和扩散距离延长)对吸收的影响被表观粘膜表面积增大的影响所克服。先用无底物、含瓜尔豆胶的溶液灌注,然后用含安替比林和MG的无瓜尔豆胶溶液灌注,由于灌注后留下额外的粘性瓜尔豆胶层,这些底物的出现率增加受到了抑制。通过向封闭的空肠段注射0.5 ml溶液实现肠壁的持续扩张。向注射溶液中添加碳水化合物(粘度约为100 cSt),安替比林、苯甲酸和MG的扩散系数降低3%至20%,吸收也降低。尿素和苄胺的扩散系数降低5%至12%;吸收变化范围在对照值(-22%至+43%)之间。模型分析表明,在大鼠封闭的空肠段中,安替比林、苯甲酸和MG吸收过程中的限速步骤是上皮前扩散阻力;因此,吸收的降低大致与扩散系数的降低相对应。对于尿素和苄胺,上皮前扩散阻力仅占总渗透阻力的20%:因此,聚合物对吸收的影响并不总是显著的。

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