丙酸可恢复 2 型糖尿病实验模型中胃底粘蛋白的分泌

T.R. Kerimov, S. Savosko, S.M. Smirnov, L.V. Natrus
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摘要

2 型糖尿病(T2DM)伴有多种并发症,尤其是胃肠道功能障碍。T2DM 大鼠胃黏膜黏蛋白分泌受损可能会影响药物在胃中的吸收,也可能是治疗和纠正疗效不佳的原因。我们的工作旨在研究 T2DM 和二甲双胍联合丙酸盐给药后大鼠胃底粘膜粘蛋白分泌的变化。大鼠的 T2DM 模型是通过连续 3 个月的高脂饮食和单次注射链脲佐菌素(25 毫克/千克)来实现的。通过胃内给药二甲双胍(60 毫克/千克)、丙酸盐(60 毫克/千克)以及联合给药上述药物,对大鼠进行为期 14 天的药物矫正。通过组织化学方法评估了胃黏膜的结构变化和黏多糖的分泌活性。对MUC5AC的表达进行了Western印迹分析。在大鼠的下胃中观察到粘蛋白分泌明显减少,这与积极分泌酸性粘多糖的细胞密度下降有关。给患有 T2DM 的动物服用二甲双胍并不能恢复胃底粘蛋白的分泌,而服用丙酸盐则会增加酸性粘多糖的分泌。在 T2DM 中发现粘液的中性成分和 MUC5AC 增加。联合使用二甲双胍和丙酸盐有助于减少这种粘蛋白的含量。已发现的胃底形态功能变化需要进一步研究,在使用口服降糖药物时应加以考虑,因为粘蛋白屏障层的缺失可能会影响胃粘膜的状态和药物的吸收。
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PROPIONIC ACID RESTORES MUCIN SECRETION IN THE GASTRIC FUNDUS IN AN EXPERIMENTAL MODEL OF TYPE 2 DIABETES
Type 2 diabetes mellitus (T2DM) is associated with a number of complications, in particular, gastrointestinal tract dysfunction. Impaired mucin secretion by the gastric mucosa in rats with T2DM may affect the absorption of drugs in the stomach and may explain the poor efficacy of treatment and correction of the condition. The aim of our work was to study changes in mucin secretion by the mucous membrane of the gastric fundus in rats with T2DM and the administration of metformin in combination with propionate. T2DM was modelled in rats by a high-fat diet for 3 months with a single administration of streptozotocin (25 mg/kg). Pharmacological correction was performed by intragastric administration of metformin (60 mg/ kg), propionate (60 mg/kg), and combined administration of the mentioned drugs for 14 days. Structural changes in the gastric mucosa and mucopolysaccharide secretion activity were assessed by histochemistry. Western blot analysis of MUC5AC expression was performed. A significant decrease in mucin production was observed in the lower stomach of rats, which was associated with a decrease in the density of cells actively producing acidic mucopolysaccharides. Metformin administration to animals with T2DM did not restore mucin production in the gastric fundus, whereas propionate administration increased acid mucopolysaccharide secretion. An increase in the neutral component of mucus and MUC5AC was found in T2DM. The combined administration of metformin and propionate helped to reduce the content of this mucin. The identified morphofunctional changes in the gastric fundus require further research and should be taken into account when using oral hypoglycaemic drugs because the loss of the mucin barrier layer may affect the state of the gastric mucosa and the absorption of drugs.
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