胰高血糖素样肽-2对梗阻性黄疸时肠道屏障功能的影响

Effect of Glucagon-like Peptide-2 (GLP-2) on Intestinal Barrier Function in Bile Duct Ligated Rats

目的探讨胰高血糖素样肽-2(GLP-2)对梗阻性黄疸模型大鼠肠道屏障功能的影响。方法将72只SD大鼠随机分为3组:实验组(T组,n=24)、手术对照组(C组,n=24)和假手术组(SO组,n=24),T组和C组双重结扎胆总管,建立梗阻性黄疸模型,SO组开腹但不结扎胆总管;结扎后,T组腹腔注射GLP-2 250μg/(kg.d),C组和SO组注射等体积0.01 mol/L的PBS溶液,于手术后第1、3、7 d分别分批处死动物。应用免疫组织化学方法检测肠黏膜增殖细胞核抗原(PCNA)和caspase-3的表达,并在光镜下观测HE染色切片肠绒毛高度。结果 C组肠黏膜PCNA的表达于术后逐渐减少,差异有统计学意义(P<0.05),且其表达量较SO组和T组减少(P<0.05),特别是第3、7 d时,比SO组和T组降低更明显(P<0.05);而C组caspase-3表达量增加显著,在术后各时间点与T组和SO组比较差异均有统计学意义(P<0.05),并且肠黏膜caspase-3的表达量在术后随时间逐渐增加(P<0.05),同时大鼠肠黏膜绒毛高度较SO组和T组变短(P<0.05),并随时间的延长逐渐缩短(P<0.05),但SO组和T组术后肠绒毛高度无明显差异。结论 GLP-2可以刺激梗阻性黄疸时肠黏膜细胞生长,促进黏膜细胞的增殖,阻止肠黏膜细胞的凋亡,起到了保护肠道屏障功能的作用。

Objective To investigate the effect of glucagonlike peptide-2（GLP-2） on intestinal barrier function in tbile duct ligated rats.Methods Seventy-two SD rats were randomly divided into three groups： GLP-2 treated group（T）,obstructive jaundice control group（C） and sham operation group（SO）.Proliferating cell nuclear antigen（PCNA） and caspase-3 expression in the intestinal mucosa were measured by immunohistochemistry staining equiped image analyzing systems（Image proplus Version 4.5）,and the height of the intestinal villi was observed and measured with light microscope,in the rats 1,3 and 7 days after operation.Results The expression of PCNA in the intestinal villi of rats in C group decreased significantly（P〈0.05）,which was more serious than those in the SO and T groups especially on the third and seventh day after operation（P〈0.05）. Compared with the SO and T groups,the expression of caspase-3 in the rats of C group increased significantly.The expression of caspase-3 increased with timeafter operation（P〈0.05）.The height of the villi of the rats in C group was shorter than those of the rats in SO and T groups,and it became shorter and shorter day by day（P〈0.05）.The height of the intestinal villi of the rats in SO group and T groups had no significant changes post operation.Conclusion GLP-2 may stimulate the growth of intestinal mucosa,increase the intestinal mucosa cell proliferation,diminish the number of the apoptosis cells,and protect the intestinal barrier function in obstructive jaundice rats.