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糖尿病大鼠小肠和结肠中晚期糖基化终产物及其受体的表达上调。

Up-regulated expression of advanced glycation end-products and their receptor in the small intestine and colon of diabetic rats.

机构信息

Mech-Sense, Aalborg Hospital, Sdr Skovvej 15, 9000 Aalborg, Denmark.

出版信息

Dig Dis Sci. 2012 Jan;57(1):48-57. doi: 10.1007/s10620-011-1951-0. Epub 2011 Nov 6.

DOI:10.1007/s10620-011-1951-0
PMID:22057282
Abstract

BACKGROUND AND AIMS

Gastrointestinal disorders and symptoms are common in diabetic patients. Advanced glycation end-products (AGEs) and their receptor (RAGE) have been proposed as an important pathological mechanism underlying diabetic complications, such as diabetic cardiopathy, retinopathy, nephropathy, etc. The aims were to study the distribution of AGE and RAGE in the normal and diabetic small intestine and colon in rats and the possible relationship between AGEs/RAGE and diabetes-induced intestinal structural remodeling.

METHODS

Diabetic and age-matched normal rats survived for 56 days. The body weight and blood glucose were measured regularly until day 56. Jejunal, ileal, and colonic segments were excised. The wet weight per unit length and the layer thickness were measured. AGE and RAGE were detected by immunohistochemical staining.

RESULTS

The wet weight per unit length in the three segments and the layer thickness in jejunum and ileum increased in the diabetic rats. The staining density of AGE in diabetic rats was higher in the villi of jejunum and ileum, and in the crypt and circumferential muscle layer of ileum compared to normal rats. The staining intensity of RAGE increased in ganglia, crypt, and brush border of diabetic jejunum and ileum as well as in ganglia of diabetic colon. Positive association was found between the accumulation of AGE and RAGE and the thickness of the different layers.

CONCLUSIONS

The expression of AGE and RAGE is up-regulated in the small intestine and colon of diabetic rats. The increased AGE and RAGE levels may contribute to diabetic GI dysfunction.

摘要

背景与目的

胃肠道疾病和症状在糖尿病患者中很常见。晚期糖基化终产物(AGEs)及其受体(RAGE)被认为是糖尿病并发症(如糖尿病性心脏病、视网膜病变、肾病等)的重要病理机制之一。本研究旨在探讨 AGE 和 RAGE 在正常和糖尿病大鼠小肠和结肠中的分布,以及 AGEs/RAGE 与糖尿病诱导的肠道结构重塑之间的可能关系。

方法

糖尿病大鼠和年龄匹配的正常大鼠分别存活 56 天。定期测量体重和血糖,直至第 56 天。切除空肠、回肠和结肠段。测量单位长度的湿重和各层厚度。通过免疫组化染色检测 AGE 和 RAGE。

结果

糖尿病大鼠三个肠段的单位长度湿重和空肠、回肠的各层厚度均增加。与正常大鼠相比,糖尿病大鼠空肠和回肠绒毛、回肠隐窝和环形肌层的 AGE 染色密度更高。糖尿病空肠和回肠的神经节、隐窝和刷状缘以及糖尿病结肠的神经节中 RAGE 染色强度增加。AGE 和 RAGE 的积累与不同层的厚度之间存在正相关关系。

结论

糖尿病大鼠小肠和结肠中 AGE 和 RAGE 的表达上调。AGE 和 RAGE 水平的升高可能导致糖尿病患者的胃肠道功能障碍。

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