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目的:探讨胰高血糖素样肽-2(GLP-2)对全肠外营养(TPN)小鼠肠黏膜结构与肝功能的影响及相关机制。方法:将30只小鼠随机分为三组,即自由进食组(Chow组)、TPN组和TPN+GLP-2组。小鼠经颈外静脉置管2 d后,TPN组接受TPN液,TPN+GLP-2组除输注等量上述营养液外,还经颈外静脉注射60μg/d的GLP-2。第7天处死小鼠,取眼球静脉血检测肝功能,留取十二指肠、回肠末端和肝组织,检测相关蛋白和mRNA表达,并观察肠黏膜和肝组织的形态学改变。结果:7 d后,TPN组小鼠体重明显下降,小肠绒毛高度与隐窝深度均劣于TPN+GLP-2组和Chow组(P<0.05)。TPN组小鼠肠黏膜损伤较严重(P<0.05),其血清肝功能指标水平较TPN+GLP-2组和Chow组高(P<0.05),而清蛋白水平较其他两组低(P<0.05)。病理显示TPN组小鼠肝细胞变性坏死,小肠微绒毛稀少,排列不齐,出现倒伏、脱落,上皮细胞线粒体破坏严重,内有大量空泡。TPN+GLP-2组肠PCNA蛋白表达较TPN组多(P<0.05),而cleaved caspase-3表达较少(P<0.05)。TPN+GLP-2组肠LGR-5 mRNA表达较TPN组多(P<0.05),而肝GRP94 mRNA表达较低(P<0.05)。结论:GLP-2可减轻TPN治疗引起的小鼠肠黏膜损伤,对维护肝功能有一定的保护作用。
Objective: To investigate the effect of glucagon-like peptide-2 (GLP-2) on intestinal mucosal structure and liver function in mice with total parenteral nutrition (TPN) and its related mechanism. Methods: Thirty mice were randomly divided into three groups: Chow group, TPN group and TPN + GLP-2 group. After 2 days of external jugular vein catheterization, TPN group received TPN solution. TPN + GLP-2 group received 60μg / d of GLP-2 via the external jugular vein in addition to the same nutrient solution. The mice were sacrificed on the 7th day, the liver function was detected by ophthalmological venous blood, the duodenum, the terminal ileum and the liver tissue were collected to detect the expression of related protein and mRNA, and the morphological changes of intestinal mucosa and liver were observed. Results: After 7 days, the body weight of TPN mice decreased significantly. The villus height and crypt depth of TPN group were both lower than that of TPN + GLP-2 group and Chow group (P <0.05). Compared with TPN + GLP-2 group and Chow group, TPN group had more severe intestinal damage (P <0.05), and serum albumin level was lower in TPN group than in other two groups (P < 0.05). Histopathology showed that the liver cells of mice in TPN group were degenerated and necrotic, with few microvilli in the small intestine, irregular arrangement, lodging and shedding, and severe mitochondria destruction in epithelial cells with a large number of vacuoles. The expression of PCNA protein in TPN + GLP-2 group was more than that in TPN group (P <0.05), while the expression of cleaved caspase-3 was less (P <0.05). The expression of LGR-5 mRNA in TPN + GLP-2 group was more than that in TPN group (P <0.05), while the expression of GRP94 mRNA in liver was lower (P <0.05). Conclusion: GLP-2 can reduce the damage of intestinal mucosa induced by TPN in mice and protect the liver function.