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年龄如何改变小鼠胃肠道中神经内分泌肽的含量。

How age changes the content of neuroendocrine peptides in the murine gastrointestinal tract.

作者信息

El-Salhy M, Sandström O

机构信息

Section for Gastroenterology and Hepatology, Department of Medicine, University Hospital, Umeå, Sweden.

出版信息

Gerontology. 1999 Jan-Feb;45(1):17-22. doi: 10.1159/000022050.

Abstract

BACKGROUND

Motility disorders in the gastrointestinal tract increase with ageing, and colorectal carcinoma is a tumor of the middle-aged and elderly. Gastrointestinal secretion, absorption, motility, cell proliferation, local immune defense and blood flow are all regulated by the neuroendocrine peptides. It is conceivable that gastrointestinal disorders at an advanced age may be accompanied by changes in this regulatory system.

OBJECTIVE

To ascertain possible age-related changes in neuroendocrine peptides in a rodent animal model.

METHODS

The concentrations of various neuroendocrine peptides were determined by radioimmunoassays in tissue extracts from the antrum, duodenum and colon of mice in four different age groups: 1, 3, 12 and 24 months. The neuroendocrine peptides investigated were: secretin, gastric inhibitory polypeptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, vasoactive intestinal polypeptide (VIP), substance P, neuropeptide Y (NPY), galanin and neurotensin.

RESULTS

Antrum: Concentrations of somatostatin, VIP and substance P decreased significantly in 1-month-old mice (but that of neurotensin increased) compared with 3-month-old mice. In 12-month-old and 24-month-old mice, concentrations of gastrin, somatostatin, VIP, substance P, NPY, galanin and neurotensin all decreased vis-à-vis 3-month-old mice. Duodenum: Whereas the levels of secretin, GIP and neurotensin increased, those of gastrin, motilin, somatostatin, VIP, substance P, NPY and galanin decreased in 1-month-old mice vis-à-vis 3-month-old mice. In both 12-month-old and 24-month-old mice, the concentrations of secretin and GIP increased, compared with those of 3-month-old mice. The levels of gastrin, motilin, somatostatin, VIP, NPY and galanin decreased in both 12-month-old and 24-month-old mice vis-à-vis 3-month-old mice. Substance P and neurotensin concentrations decreased in 12-month-old mice, but not in 24-month-old mice. Colon: In 1-month-old mice the levels of PYY, somatostatin, VIP, substance P and galanin decreased vis-à-vis 3-month-old mice. In 12-month-old mice, the concentrations of PYY, somatostatin, VIP, NPY, galanin and neurotensin decreased compared with those in 3-month-old mice. In 24-month-old mice, the VIP level decreased, whereas the substance P level increased.

CONCLUSION

The changes in neuroendocrine peptides observed in the gastrointestinal tract of this murine animal model could be of some relevance for the increased gastrointestinal dysfunction in the elderly human. They may also be involved in the development of colorectal cancer.

摘要

背景

胃肠道动力障碍随年龄增长而增加,结直肠癌是一种中老年肿瘤。胃肠分泌、吸收、动力、细胞增殖、局部免疫防御和血流均受神经内分泌肽调节。可以想象,老年时的胃肠功能紊乱可能伴随着这种调节系统的变化。

目的

在啮齿动物模型中确定神经内分泌肽可能的年龄相关变化。

方法

采用放射免疫分析法测定四个不同年龄组(1、3、12和24个月)小鼠胃窦、十二指肠和结肠组织提取物中各种神经内分泌肽的浓度。所研究的神经内分泌肽包括:促胰液素、胃抑制多肽(GIP)、胃泌素、胃动素、肽YY(PYY)、生长抑素、血管活性肠肽(VIP)、P物质、神经肽Y(NPY)、甘丙肽和神经降压素。

结果

胃窦:与3个月大的小鼠相比,1个月大的小鼠生长抑素、VIP和P物质浓度显著降低(但神经降压素浓度升高)。与3个月大的小鼠相比,12个月大和24个月大的小鼠胃泌素、生长抑素、VIP、P物质、NPY、甘丙肽和神经降压素浓度均降低。十二指肠:与3个月大的小鼠相比,1个月大的小鼠促胰液素、GIP和神经降压素水平升高,而胃泌素、胃动素、生长抑素、VIP、P物质、NPY和甘丙肽水平降低。与3个月大的小鼠相比,12个月大和24个月大的小鼠促胰液素和GIP浓度均升高。与3个月大的小鼠相比,12个月大和24个月大的小鼠胃泌素、胃动素、生长抑素、VIP、NPY和甘丙肽水平均降低。12个月大的小鼠P物质和神经降压素浓度降低,但24个月大的小鼠未降低。结肠:与3个月大的小鼠相比,1个月大的小鼠PYY、生长抑素、VIP、P物质和甘丙肽水平降低。与3个月大的小鼠相比,12个月大的小鼠PYY、生长抑素、VIP、NPY、甘丙肽和神经降压素浓度降低。24个月大的小鼠VIP水平降低,而P物质水平升高。

结论

在该小鼠动物模型胃肠道中观察到的神经内分泌肽变化可能与老年人类胃肠道功能障碍增加有关。它们也可能参与结直肠癌的发生发展。

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