胰高血糖素样肽-2对小鼠急性胰腺炎相关肠炎的保护性作用及机制

Protective effect and mechanism of glucagon-like peptide-2 on acute pancreatitisassociated enteritis in mice

目的采用小鼠动物模型探究胰高血糖素样肽-2(glucagon like peptide-2,GLP-2)对急性胰腺炎相关肠炎的保护性作用及机制。方法将总数为40只的雄性实验小鼠,严格按照随机分配原则,分为对照模型组即胰腺炎组及GLP-2治疗组两组,每组各20只。通过腹腔内注射L-精氨酸法建立AP的模型,并在制模后30 min,GLP-2治疗组按照0.25mg/kg的剂量通过腹腔注射GLP-2方式进行处理,间隔时间为12 h,连续使用3 d;而AP组模型则是使用相同剂量的生理盐水进行处理。3 d后对两组所有小鼠进行处死,采用H&E、免疫荧光及免疫印迹法等评估检测小鼠肠道标本中炎性水平及肠粘膜细胞凋亡情况;检测TNF-α、IL-16、IL-10水平,进行炎性评分,对比各组小鼠肠道炎症情况。结果肠道黏膜的炎性介质水平,可见GLP-2治疗组TNF-α及IL-6含量绝对低于AP组小鼠(P<0.05),IL-10的含量则较高于AP组小鼠(P<0.05),而治疗组肠道组织炎性评分结果则低于AP组(P<0.05);Western blot检测显示治疗组肠道组织细胞发生凋亡现象的量相对于对照组大为减少(P<0.05)。结论我们的研究证实GLP-2对于急性胰腺炎小鼠相关肠炎具有一定程度的保护性作用。

Objective The mouse animal model was used to investigate the protective effect and mechanism of glucagon like peptide-2(GLP-2)on acute pancreatitis-associated enteritis.Methods A total of 40 male experimental mice were randomly divided into a control model group,that is,a pancreatitis group and a GLP-2 treatment group,to ensure that there were 20 mice in each group.The model of AP was established by intraperitoneal injection of L-arginine,and 30 minutes after modeling,mice in the GLP-2 treatment group was treated by intraperitoneal injection of GLP-2 at a dose of 0.25 mg/kg,with an interval of 12 h continuously for 3 days,while the AP modelgroup was treated with the same dose of normal saline.3 days later,all the mice in the two groups were sacrificed,and the inflammation and apoptosis of intestinal mucosal cellsin the intestinal specimens of the mice was evaluated by H&E staining,immunofluorescence and immunoblotting method.The levels of TNF-α,IL-16 and IL-10 were used to evaluate inflammation scores,and the levels of intestinal inflammation were compared between the groups.Results The level of inflammatory mediators in the intestinal mucosal showed that the levels of TNF-αand IL-6 in the GLP-2 treatment group were significantly lower than those in the AP group(P<0.05),while the IL-10 content was higher than that in the AP group(P<0.05),the intestinal tissue inflammation score in the treatment group was lower than that in the AP group(P<0.05).Western blot analysis showed that the amount of apoptosis in the intestinal tissue of the treatment group was significantly reduced compared with the control group(P<0.05).Conclusions Our study confirms that GLP-2 has a protective effect on acute pancreatitisassociated enteritisin mice.