胰高血糖素样肽-2对烧伤大鼠肠粘膜细胞增殖的影响

Influence of glucagon-like peptide-2 on the proliferation of the intestinal mucosal cells in scalded rats

目的 探讨胰高血糖素样肽 2 (GLP 2 )对烧伤大鼠肠粘膜细胞增殖及肠粘膜结构的影响。 方法 5 5只Wistar大鼠随机分为烧伤组、GLP 2组 (烧伤后经GLP 2处理 ,2 0 0 μg/kg ,2次 /d腹腔注射 )与正常对照组。前两组动物于 30 %TBSAⅢ度烧伤后 6、12h及 1、3、5d分别处死 ,另处死正常对照组大鼠。检测各组增殖细胞核抗原 (PCNA)、细胞周期蛋白CyclinD的表达情况以及血浆二胺氧化酶 (DAO)的活性 ,并行肠粘膜组织学观察。 结果 与正常对照组比较 ,烧伤组伤后 6、12hPCNA表达稍有增强 ,伤后 1d减弱 ,3d时最低 ,5d时仍低于正常 ;GLP 2组PCNA表达的变化在伤后早期与烧伤组基本一致 ,但伤后 3、5d时强于烧伤组。烧伤组大鼠肠粘膜CyclinD蛋白在伤后 6、12h略有升高 ,但 1d时迅速下降至伤前的 4 0 % ,而GLP 2组CyclinD蛋白表达在伤后 1、3、5d高于烧伤组。大鼠烧伤后血浆DAO活性明显升高 ,经GLP 2治疗 5d后该指标明显降低 (P <0 .0 1)。组织学观察见GLP 2组肠绒毛排列较为规则 ,长短较一致 ,未见明显的上皮脱落。 结论 大鼠烧伤后腹腔给予外源性GLP 2能减轻肠粘膜损伤 ,其机制可能与GLP 2使PCNA、ClyclinD表达增加、促进受损肠粘膜细胞增殖有关。

Objective To explore the influence of glucagon like peptide 2 (GLP 2) on the proliferation of the intestinal mucosal cells in scalded rats. Methods Fifty five Wistar rats were employed in the study and were randomly divided into normal control (C), simple scald ( S) and scald with GLP 2 treatment (G) groups. The rats in G group received GLP 2 introperitoneally in a dose of 200 μg/kg two times a day. The rats in S and G groups were sacrificed at 6 postburn hours (PBHs), 12 PBHs, 1 postburn day (PBD1),PBD3 and PBD5 and the rats in C group were also sacrificed.Plasma diamine oxidase (DAO) activity,cell cycle protein cyclin D expression and the proliferating cell nuclear antigen (PCNA) in all groups were determined. And the histological change in the intestinal mucosal tissue was observed simultaneously.with all the abovedeterminations.Results Compared with those in C group, the PCNA expression at 6 and 12 PBHs in S group was enhanced slightly and weakened at PBD1,reaching the lowest level at PBD3 and it was still lower than that in C group at PBD5. Changes in PCNA in G group were similar to that in S group,except that the expression at PBD3 and PBD5 was stronger than that in S group. The intestinal mucosal cyclin D protein expression was increased at 6 and 12 PBHs in S group, but decreased by 40% before injury at PBD1. Nevertheless, the cyclin D protein expression in G group was much higher than that in S group at PBD1, PBD3 and PBD5. The plasma DAO activity increased significantly in rats after burn injury. But the activity decreased obviously after GLP 2 treatment for 5 days (P<0.01). It was observed histologically in G group that the lining of Exogenous intestinal villi was regular and well arranged without evident epithelial exfoliation. Conclusion Exogenous GLP 2 might ameliorate intestinal mucosal injury in scalded rats,and promotion of the expression of PCNA and cyclin D,resulting in proliferation of injured intestinal mucosal cells,might be the underlying mechanisms. [