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小肠黏膜对口服糖皮质激素的反应。

Response of the small intestinal mucosa to oral glucocorticoids.

作者信息

Batt R M, Scott J

出版信息

Scand J Gastroenterol Suppl. 1982;74:75-88.

PMID:6959244
Abstract

These studies explored the effects of oral pharmacological doses of glucocorticoids on the normal small intestine of the adult rat. Short-term (7 days) prednisolone had little effect on mucosal structure or cell kinetics but enhanced the maximum absorptive capacities of the jejunum and ileum for galactose. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. Activities of brush border enzymes were elevated and turnover studies indicated an increased rate of synthesis of brush border proteins associated with an enhanced glycoprotein content of the microvillus membrane. Subcellular fractionation studies demonstrated a large increase in the membrane-bound ribosomal RNA content of the enterocytes consistent with an enhanced synthesis of membrane proteins. These findings implicate a direct action of prednisolone on the enterocytes to increase their absorptive and digestive capacities by the induction of specific functional proteins. These effects on the absorptive and digestive functions of the small intestine were sustained with long-term (28 days) prednisolone feeding. An equivalent long-term oral dose of betamethasone-17-valerate, a locally rather than a systemically active glucocorticoid, had a similar effect on the enterocytes. However, an inhibition of crypt cell turnover resulted in a marked hypoplasia and hence no net change in the functional capacity of the mucosa. These findings emphasise the separate and opposing actions of glucocorticoids on the adult mucosa, on the one hand to stimulate enterocyte function, but on the other to reduce the enterocyte population. The predominant activity appears to be a function of each individual steroid. The predominant stimulatory action of prednisolone was further emphasised by investigating the effects of this glucocorticoid on the adapted ileum following jejunal resection. Indeed, short-term prednisolone enhanced the adaptive hyperplasia in the ideal remnant by increasing the functional capacity of the expanded population of enterocytes.

摘要

这些研究探讨了口服药理剂量的糖皮质激素对成年大鼠正常小肠的影响。短期(7天)泼尼松龙对黏膜结构或细胞动力学影响不大,但增强了空肠和回肠对半乳糖的最大吸收能力。这是由于单个肠细胞中载体介导的转运增加,而非细胞群体的变化。刷状缘酶的活性升高,周转研究表明,与微绒毛膜糖蛋白含量增加相关的刷状缘蛋白合成速率加快。亚细胞分级分离研究表明,肠细胞中膜结合核糖体RNA含量大幅增加,这与膜蛋白合成增强一致。这些发现表明泼尼松龙对肠细胞有直接作用,通过诱导特定功能蛋白来增加其吸收和消化能力。长期(28天)给予泼尼松龙可维持对小肠吸收和消化功能的这些影响。等效的长期口服剂量的倍他米松-17-戊酸酯,一种局部而非全身活性的糖皮质激素,对肠细胞有类似作用。然而,隐窝细胞周转的抑制导致明显的发育不全,因此黏膜功能能力无净变化。这些发现强调了糖皮质激素对成年黏膜的不同且相反的作用,一方面刺激肠细胞功能,另一方面减少肠细胞数量。主要活性似乎是每种甾体的一种功能。通过研究这种糖皮质激素对空肠切除术后适应性回肠的影响,进一步强调了泼尼松龙的主要刺激作用。事实上,短期泼尼松龙通过增加扩大的肠细胞群体的功能能力,增强了理想残余肠段的适应性增生。

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