Scott R B, Kirk D, MacNaughton W K, Meddings J B
Gastrointestinal Research Group, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada T2N 1N4.
Am J Physiol. 1998 Nov;275(5):G911-21. doi: 10.1152/ajpgi.1998.275.5.G911.
To determine whether treatment with a potent protease-resistant analog of human glucagon-like peptide 2 (GLP-2) might augment the adaptive response to massive intestinal resection, rats were divided into resected, which had 75% of the midjejunoileum removed, sham-resected, and nonsurgical groups. Within each group, animals were assigned to 21 days of treatment with the drug (0.1 micrograms/g of the GLP-2 analog in phosphate-buffered saline) or vehicle alone subcutaneously twice daily. Food intake; weight gain; jejunal and ileal diameters, total and mucosal wet weights per centimeter, crypt depths, and villus heights; mucosal sucrase activity, milligrams of protein per centimeter, and micrograms of DNA per centimeter; and D-xylose absorption were measured. There was a significant increase in diameter, total and mucosal wet weights per centimeter, crypt-villus height, sucrase activity, milligrams of protein per centimeter and micrograms of DNA per centimeter in both the jejunum and ileum in response to resection and a significant additive response to the GLP-2 analog in the jejunum but not in the ileum. The ratio of milligrams of protein per centimeter to micrograms of DNA per centimeter of mucosa was not different among groups, consistent with hyperplasia. D-Xylose absorption was significantly reduced in response to resection; however, the GLP-2 analog enhanced the absorptive capacity in control animals and restored the absorptive capacity in resected animals. Thus the GLP-2 analog induces mucosal hyperplasia and enhances the rate and magnitude of the proximal intestinal adaptive response to massive resection.
为了确定用一种对蛋白酶有抗性的强效人胰高血糖素样肽2（GLP-2）类似物进行治疗是否可能增强对大面积肠切除的适应性反应，将大鼠分为切除组（切除75%的空肠中段回肠）、假切除组和非手术组。在每组中，动物被分配接受21天的药物治疗（在磷酸盐缓冲盐水中的0.1微克/克GLP-2类似物）或仅皮下注射赋形剂，每天两次。测量食物摄入量、体重增加、空肠和回肠直径、每厘米的总湿重和黏膜湿重、隐窝深度和绒毛高度、黏膜蔗糖酶活性、每厘米的蛋白质毫克数和每厘米的DNA微克数以及D-木糖吸收情况。切除后，空肠和回肠的直径、每厘米的总湿重和黏膜湿重、隐窝-绒毛高度、蔗糖酶活性、每厘米的蛋白质毫克数和每厘米的DNA微克数均显著增加，并且空肠对GLP-2类似物有显著的相加反应，而回肠则没有。各组黏膜每厘米蛋白质毫克数与每厘米DNA微克数的比值无差异，符合增生表现。切除后D-木糖吸收显著降低；然而，GLP-2类似物增强了对照动物的吸收能力，并恢复了切除动物的吸收能力。因此，GLP-2类似物可诱导黏膜增生，并增强近端肠道对大面积切除的适应性反应的速率和程度。
