胰高血糖素样肽-2对脓毒症大鼠肠黏膜通透性的影响

目的探讨胰高血糖素样肽-2（GLP-2）对脓毒症大鼠肠黏膜通透性的影响。方法采用腹腔注射内毒素（5mg／kg）的方法制作脓毒症模型，根据预实验结果选取病理变化最严重的注射后6h作为实验时间点。成年雄性SD大鼠60只，按数字表法随机分为生理盐水对照组（A组）、脓毒症组（B组）、治疗组（C组）3组，每组20只。A、B、C组分别以生理盐水、脂多糖（LPS）、GLP-2＋LPS腹腔注射于大鼠模型；于注射后6h摘眼球取血，紫外分光光度法检测D-乳酸含量，留取末端回肠组织用免疫组化法检测紧密连接蛋白occludin表达，同时观察肠黏膜病理（HE染色）改变。结果光镜下A组肠黏膜未见明显病理改变；B组肠黏膜明显充血水肿，上皮细胞部分变性、坏死脱落，并有大量炎细胞浸润；C组肠黏膜病理改变较B组明显减轻。A组occludin蛋白沿着细胞膜的顶端呈线状连续分布，B组occludin蛋白分布不均，染色变淡，C组occludin蛋白表达连续性部分恢复，染色变深。B组血液中D-乳酸含量（8．14±0．91）mg／L，高于A组的（3．98±0．68）mg／L和C组的（6．46±0．73）mg／L，差异均有统计学意义（F=144．12，P值均〈0．01）。结论脓毒症大鼠肠黏膜屏障受损，通透性增加；GLP-2可以减轻脓毒症大鼠肠道屏障功能损伤的程度，对脓毒症的肠道损伤有一定治疗作用。

Effects of glucagon-like peptide-2 on intestinal barrier permeability in rats with sepsis

Objective To evaluate the effects of glucagon like peptide-2 （GLP-2） on intestinal barrier permeability in rats with sepsis. Methods Sepsis model was estabished by injecting lipopolysaccharide （5 mg/kg） intraperitoneally. Six hours of injection with the most serions pathological changes was chosen as the experimental time point according to the results of precimirary experiments. Healthy male Spragne-Dawley rats, were randomly divided into three experimental groups： normal control group （ group A） were injected with normal saline intraperitoneally, lipopolysaccharide （LPS） group （ group B） and LPS ＋ GLP-2 group （group C ） were intraperitoneally treated with LPS and LPS plus GLP-2 respectively. Terminal ileum of each rat was collected for the observation of the pathologic changes of intestinal mucosa under optical micoscope （hematoxylin-eosin staining）. The expression of occludin was analyzed by immunohistochemistry. Eye ball blood was tested for D-lactate by ultraviolet spectrophomotometry. Results There was no obvious abnormality in group A. While in group B, intestinal mucosa was with hyperemia and edema and was inflihrated by a great number of inflammatory cells, epithelial cells were partly apoptotic or necrotic. The above changes were alleviated in group C. The staining of occludin in group A was similar to a line, which reflected a continuous and uniform distribution localized along the apical region of the lateral plasma membrane. In group B, the distribution was uneven and the staining was weakened, the above changes were alleviated in group C. In comparison with group A, the D- lactate content was significantly increased in group B [ （8.14 ± 0.91 ） mg/L vs （3.98 ± 0.68） mg/L, P 〈 0.01 ]. As compared with group B, the D-lactate content was significantly decreased in group C [ （6.46 ± 0.73） mg/L vs （8.14 ±0.91） mg/L, F= 144.12, P〈0.01], but still not recuperated to normal level. Conclusions There is an increasing intestinal barrier permeability in rat