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目的研究糖尿病大鼠胃肠排空延迟和空回肠P物质分布的关系,及这一改变是否影响局部寡肽转运体PEPT1的水平。方法 Wistar大鼠24只,分为3组(n=8)。1型糖尿病模型加胰岛素治疗组,左脲链霉素(streptozocin,STZ)单次股静脉注射(60 mg/kg)诱导1型糖尿病模型,并每天给予1次长效胰岛素(20 U/d,皮下注射)控制血糖。1型糖尿病模型组,左脲链霉素(STZ)单次股静脉注射(60 mg/kg)诱导1型糖尿病模型,并给予等量生理盐水。正常对照组大鼠经股静脉注射生理盐水。1个月后检测胃肠排空功能,选取胃肠排空明显延迟的动物,通过免疫组化分析空肠起始段与回肠末端SP分布变化。刮取空肠起始段与回肠末端的黏膜细胞,通过免疫印迹技术检测PEPT1水平。结果糖尿病大鼠胃肠推进率低于60%的,其空肠起始段和回肠末端SP分布明显减少(P<0.05),其中SP在空肠起始段主要分布于黏膜下层,肌层未发现阳性染色,回肠末端除分布于黏膜下层外,黏膜上皮多见阳性染色。与同月龄正常大鼠及STZ加胰岛素注射非糖尿病组相比,糖尿病大鼠空肠起始段与回肠末端黏膜细胞PEPT1的表达水平显著下降(P<0.05)。结论糖尿病导致的胃排空延迟和空回肠P物质分布下调关系密切,同时也出现空肠起始端与回肠末端PEPT1的表达减少。上述变化可能和糖尿病胃肠营养不良有关。
Objective To investigate the relationship between delayed gastrointestinal emptying and substance P distribution in diabetic rats and whether this change affects the level of local oligopeptide transporter PEPT1. Methods Twenty-four Wistar rats were divided into three groups (n = 8). Type 1 diabetes mellitus plus insulin treatment group, type 1 diabetes mellitus model induced by streptozocin (STZ) single intravenous injection (60 mg / kg), and once a day long-acting insulin (20 U / d, Subcutaneous injection) to control blood sugar. Type 1 diabetes mellitus (STZ), a single intravenous injection (60 mg / kg), induced type 1 diabetes mellitus and given the same volume of saline. Normal control rats were injected with normal saline through femoral vein. After 1 month, the gastrointestinal emptying function was tested. The animals with significantly delayed gastrointestinal emptying were selected, and the changes of SP distribution in the initial and the distal ileum were analyzed by immunohistochemistry. Scratch the beginning of jejunum and the end of the ileum mucosal cells detected by Western blot PEPT1 levels. Results The gastrointestinal propulsion rate was lower than 60% in diabetic rats, and the distribution of SP in the initial and the distal jejunum was significantly decreased (P <0.05). The SP in the initial stage of jejunum mainly distributed in the submucosa but not in the muscle Dyeing, in addition to the terminal ileum located in the submucosa, mucosal epithelial more common positive staining. Compared with the normal rats of the same age and STZ plus insulin-injected non-diabetic group, the expression level of PEPT1 in the initial stage of jejunum and the terminal ileum of diabetic rats was significantly decreased (P <0.05). Conclusions The delay of gastric emptying caused by diabetes is closely related to the down-regulation of substance P in the ileum. At the same time, the expression of PEPT1 at the beginning and the end of the ileum also decreases. The above changes may be related to gastrointestinal malnutrition in diabetes.