胰高糖素样肽2对肠道缺血再灌注小鼠黏膜免疫变化的影响

Effect of glucagon-like peptide 2 on the intestinal mucosal immunity and correlative cytokines in mice with gut ischemia/reperfusion injury

目的观察胰高糖素样肽2(GLP-2)对小鼠肠道缺血再灌注后肠黏膜免疫和相关细胞因子的影响。方法70只ICR小鼠被随机分为正常组(N组)、缺血再灌注组(C组)和GLP-2治疗组(T组)(200μg/kg皮下注射,2次/d)。于术后1、3、5d处死动物,检测肝脏、脾脏和肠系膜淋巴结细菌易位率、血浆内毒素水平和肠道灌洗液免疫球蛋白(Ig)A水平,并测定肠黏膜Th1/Th2因子的变化。结果缺血再灌注后,C组动物的细菌易位率(100%)和血浆内毒素水平[(0.753±0.044)EU/m]明显高于T组,也显著高于N组(均P=0.000)。C组IgA水平在I/R后1d降至低谷,3、5d仍处于低值。T组IgA水平下降后,3、5d迅速回升至正常范围,显著高于C组水平。C组Th1因子(IFN-γ、IL-2)在I/R后持续升高,Th2因子(IL-4、IL-10)先明显下降后逐渐回升。T组Th1/Th2细胞因子的时间变化曲线和C组相似,但是Th1因子的升幅小于C组,Th2因子的降幅小,并在5d恢复或接近正常。结论GLP-2在一定程度上可以保护缺血再灌注后的肠黏膜免疫功能,这可能和它维护肠黏膜Th1/Th2因子平衡有关。

Objective To investigate the effect of glucagon-like peptide 2 on intestinal mucosa immunity after ischemia/reperfusion injury and explore the possible mechanisms. Methods A total of 70 ICR mice were randomly divided into three groups including normal control group（N）, I/R group（C） and GLP-2 treatment group（T） （treated with GLP-2, 200 μg/kg）. The mice were sacrificed on the 1st, 3rd and 5th day after I/R injury, Liver, spleen and mensenteric lymph nodes samples were collected for bacterial culture. The endotoxin levels in plasma were also measured. Small intestine washing were obtained for IgA and the intestine homogenized were analyzed for Thl/Th2 cytokines. Results The rate of bacterial transloeation and the level of endotoxin in group C were significant higher than those in group T and group N. The IgA level in the lavage of the intestine was significantly decreased on the 1st day after I/R in group C and T compared with that in group N, while there was no difference between group C and T. The IgA level increased on the 3rd day and returned to normal on the 5th day after I/R in group T, while that in group C was still lower than normal. In group C, the levels of Thl-type （IL-2 and IFN-У） cytokines increased, the levels of Th2-type （IL-4 and IL-10） decreased significantly on the 1 st day and then increased gradually. The change pattern of cytokines levels in group T resembled that in group C, but the levels of IL-4 and IL-10 in group T returned to normal on the 5th day after I/R. Conclusions GLP-2 supplementation can partly protect the intestinal mucosal immunity. The mechanism may probably be related to the restitution of the balance of Thl/Th2 cytokines in the intestinal mucosa in mice.