CAJ | 학술논문

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(5 mg/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.
목적 탐토이고혈당소양태-2(GLP-2)대농독증대서장점막통투성적영향.방법 채용복강주사내독소(5 mg/kg)적방법제작농독증모형,근거예실험결과선취병리변화최엄중적주사후6h작위실험시간점.성년웅성SD대서60지,안수자표법수궤분위생리염수대조조(A조)、농독증조(B조)、치료조(C조)3조,매조20지.A、B、C조분별이생리염수、지다당(LPS)、GLP-2+ LPS복강주사우대서모형;우주사후6h적안구취혈,자외분광광도법검측D-유산함량,류취말단회장조직용면역조화법검측긴밀련접단백occludin표체,동시관찰장점막병리(HE염색)개변.결과 광경하A조장점막미견명현병리개변;B조장점막명현충혈수종,상피세포부분변성、배사탈락,병유대량염세포침윤;C조장점막병리개변교B조명현감경.A조occludin단백연착세포막적정단정선상련속분포,B조occludin단백분포불균,염색변담,C조occludin단백표체련속성부분회복,염색변심.B조혈액중D-유산함량(8.14±0.91) mg/L,고우A조적(3.98±0.68) mg/L화C조적(6.46±0.73) mg/L,차이균유통계학의의(F=144.12,P치균＜0.01).결론 농독증대서장점막병장수손,통투성증가;GLP-2가이감경농독증대서장도병장공능손상적정도,대농독증적장도손상유일정치료작용.
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 Sprague-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 infliltrated 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) rag/L,F =144.12,P ＜ 0.01],but still not recuperated to normal level.Conclusions There is an increasing intestinal barrier permeability in rats with sepsis and GLP-2 has protective effect on intestinal mechanical barrier.