胰高血糖素样肽-2类似物可增强缺血再灌注损伤后肠黏膜质量和吸收功能。

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury.

作者信息

Rajeevprasad R, Alavi K, Schwartz M Z

机构信息

AI. duPont Hospital for Children, Wilmington, DE 19803, USA.

出版信息

J Pediatr Surg. 2000 Nov;35(11):1537-9. doi: 10.1053/jpsu.2000.18301.

DOI:10.1053/jpsu.2000.18301

PMID:11083417

Abstract

BACKGROUND/PURPOSE: This study was designed to explore the efficacy of a synthetic analogue of glucagonlike peptide-2 (GLP-2a) in enhancing mucosal mass and absorptive function in a rat model of intestinal ischemia-reperfusion (I-R) injury.

METHODS

Each of 20 Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents over 3 days. Rats were divided into 4 groups (n = 5 per group): (1) normal intestine/saline infusion; (2) 30-minute superior mesenteric artery occlusion/saline infusion, (3) normal intestine/ GLP-2alpha infusion, and (4) 30-minute superior mesenteric artery occlusion/GLP-2alpha infusion. Subsequently, mean mucosal 14C-galactose and 14C-glycine absorption and DNA content were determined for each group.

RESULTS

In saline-treated rats, 30 minutes of mesenteric ischemia decreased mean mucosal galactose absorption by 29% (P < .05), glycine absorption by 22% (P = .12), and DNA content by 28% (P < .01) when compared with rats with uninjured intestine. In rats subjected to 30 minutes of intestinal ischemia, GLP-2alpha significantly improved galactose absorption by 46% (P < .05), glycine absorption by 84% (P < .01), and DNA content by 63% (P < .01) when compared with saline-treated control rats. In rats with mesenteric I-R injury treated with GLP-2a, galactose absorption was returned to normal. Glycine absorption and DNA content were increased significantly by 44% (P < .01) and 18% (P < .05), respectively, beyond the baseline for normal intestine.

CONCLUSIONS

Thirty minutes of intestinal ischemia followed by immediate reperfusion significantly decreased mucosal mass and absorptive function, validating this rat model of I-R injury. After mesenteric I-R, GLP-2a significantly increased mucosal DNA content and absorption of 14C-galactose and 14C-glycine when compared with untreated control rats. After I-R injury, GLP-2a restored mucosal mass and absorptive function to normal or above-normal levels.

摘要

背景/目的：本研究旨在探讨胰高血糖素样肽-2合成类似物（GLP-2a）在增强肠缺血再灌注（I-R）损伤大鼠模型黏膜质量和吸收功能方面的疗效。

方法

20只Sprague-Dawley大鼠均接受颈静脉导管置入术，该导管与皮下渗透泵相连，设计为在3天内输送其内容物。大鼠分为4组（每组n = 5）：（1）正常肠/输注生理盐水；（2）肠系膜上动脉闭塞30分钟/输注生理盐水；（3）正常肠/输注GLP-2α；（4）肠系膜上动脉闭塞30分钟/输注GLP-2α。随后，测定每组的平均黏膜14C-半乳糖和14C-甘氨酸吸收以及DNA含量。

结果

在输注生理盐水的大鼠中，与未损伤肠的大鼠相比，30分钟的肠系膜缺血使平均黏膜半乳糖吸收降低29%（P <.05），甘氨酸吸收降低22%（P =.12），DNA含量降低28%（P <.01）。在经历30分钟肠缺血的大鼠中，与输注生理盐水的对照大鼠相比，GLP-2α使半乳糖吸收显著提高46%（P <.05），甘氨酸吸收提高84%（P <.01），DNA含量提高63%（P <.01）。在用GLP-2a治疗的肠系膜I-R损伤大鼠中，半乳糖吸收恢复正常。甘氨酸吸收和DNA含量分别比正常肠基线水平显著增加44%（P <.01）和18%（P <.05）。