GLP-2 对胆总管结扎大鼠肠道细菌移位及内毒素血症的影响

目的:探讨胰高血糖素样肽2( GLP-2)对胆总管结扎大鼠肠道细菌移位和内毒素血症的影响.方法:72只SD大鼠随机均分为假手术组、模型组和GLP-2治疗组.模型组和GLP-2治疗组大鼠行胆总管结扎,术后GLP-2治疗组每天腹腔注射GLP-2[250μg/(kg·d)],假手术组和模型组以相同方式注射等体积PBS.检测各组术后1,3,7d肠黏膜磷脂酰肌醇3-激酶(PI3K)的表达,肠道细菌移位和内毒素血症发生状况.结果:与假手术组和GLP-2治疗组比较,模型组大鼠肠黏膜PI3K表达量在术后第3,7天明显降低(均P＜0.05);GLP-2治疗组PI3K表达量虽有减少,但与假手术组之间的差异无统计学意义(均P＞0.05).术后模型组大鼠肝脏和脾脏细菌移位率逐渐增加,第7天达100％,肝脏和脾脏总的细菌移位率分别为75.0％和66.7％; GLP-2治疗组两脏器细菌移位率增加缓慢,总的细菌移位率分别为37.5％和25.0％,均明显低于模型组(均P＜0.05).模型组和GLP-2治疗组门静脉血中内毒素含量均随时间的延长而逐渐增加,但GLP-2治疗组的内毒素含量在各时间点上均明显低于模型组(均P＜0.05).结论:GLP-2对胆总管结扎大鼠肠道细菌移位和内毒素血症具有抑制作用,机制可能与其增加肠黏膜中PI3K的表达,从而保护肠道屏障功能有关.

Effect of glucagon-like peptide 2 (GLP-2) on bacterial translocation and endotoxemia in rats with common bile duct ligation

Objective: To investigate the effect of glucagon-like peptide 2 (GLP-2) on bacterial translocation andendotoxemia in rats with bile duct ligation.Methods: Seventy-two SD rats were equally randomized into sham operation group, model group and GLP-2treatment group, and rats in model and GLP-2 treatment group underwent common bile duct ligation. After surgery, rats of the GLP-2 treatment group were subjected to daily intraperitoneal injection of GLP-2 [250 μg/(kg?d)], and those of the sham operation group and model group received the same volume of PBS by usingexactly the same regimen. The phosphatidylinositol 3-kinase (PI3K) expression in the intestinal mucosa, andthe bacterial translocation rate and development of endotoxemia of the rats were detected at day 1, 3, and 7after surgery.Results: The PI3K expressions in the intestinal mucosa of rats of the model group decreased significantlyat day 3 and 7 after surgery compared with those of the sham operation group or GLP-2 treatment group(all P<0.05), and although those somewhat decreased in the GLP-2 treatment group, the differences hadno statistical significance compared with sham operation group (all P>0.05). In the model group, the ratesof bacterial translocation to the liver and spleen increased gradually and both reached 100% on day 7 aftersurgery. The overall rates of bacterial translocation to the two organs were 75.0% and 66.7%, respectively. In theGLP-2 treatment group, the rates of bacterial translocation to the two organs increased slowly, and the overallrates of bacterial translocation were 37.5% and 25.0% respectively, which were significantly lower than those inthe GLP-2 treatment group (both P<0.05). The endotoxin content of the portal vein blood elevated graduallywith time in both model group and GLP-2 treatment group, but it was significantly lower in GLP-2 treatmentgroup than that in model group at each observation point (all P<0.05).Conclusion: GLP-2 has inhibitory effect on the bacterial translocation from the intestinal tract anddevelopment of endotoximia in rats with common bile duct ligation, and the mechanism is probably related toits enhancement of PI3K expression in intestinal mucosa and thereby protecting gut barrier function.