肠粘膜屏障功能在儿童过敏性紫癜病理机制中的作用

发布时间：2018-03-27 04:51

本文选题：过敏性紫癜　切入点：儿童　出处：《河北医科大学》2012年硕士论文

【摘要】：目的：过敏性紫癜(Henoch-Schonlein purpura，，HSP)是环境介导的，免疫系统参与的，遗传易感性和环境因素相互作用结果的疾病。我们的研究期望通过肠粘膜屏障功能在HSP病理机制中的作用来理解这个理论的复杂性。肠粘膜屏障包括机械屏障、生物屏障、免疫屏障和化学屏障。有研究认为，肠腔内的某些抗原成分可能参与了HSP的发生，而肠粘膜屏障可阻挡此抗原通路，识别抗原“自己”和“非己”，以形成“耐受”或“过敏”。这表明肠粘膜各组成成分包括肠道菌群成员、肠粘膜免疫成分、肠粘膜通透性等可能在过敏性和自身免疫性疾病的发生发展中发挥作用。基于上述理论，我们以检测肠道菌群结构代表肠粘膜生物屏障、检测粪便分泌型免疫球蛋白A(secretoryimmunoglobulinA，sIgA)代表肠粘膜免疫屏障、检测甘露醇和乳果糖的排泄率代表肠粘膜机械屏障，观察HSP患儿肠粘膜屏障功能变化，探讨其在HSP的作用和作用关系，为在HSP早期保护肠粘膜屏障功能阻止疾病的发生发展提供理论依据。方法：收集2011年8月-2012年2月于河北医科大学第三医院儿科就诊或住院的HSP患儿26例（平均年龄6.04±1.75岁，男孩16名，女孩10名），以及同期来我院健康查体的儿童20例（平均年龄6.23±2.12岁，男孩13名，女孩7名）。儿童HSP诊断参考1990年美国风湿病学会制订的HSP诊断标准,即：至少满足以下2个要求：首次发病年龄不超过20岁；明显紫癜；急性腹痛；粒细胞浸润小动脉或小静脉壁。所有入选儿童均在研究开始前签订知情同意书，并获河北医科大学第三医院伦理道德委员会同意。就诊次日收集粪便和尿液标本。采用16S rDNA荧光定量PCR技术分析肠道菌群。粪便中双歧杆菌和大肠杆菌的数量之比（Bifidobacteria/E. Coli，B/E）反映了肠道微生态生境。与健康对照组相比，B/E值下降提示肠道菌群失调。采用标准酶联免疫吸附试验(Enzyme Linked ImmunosorbentAssay，ELISA)测定粪便中sIgA水平。采用高效液相色谱法(high performance liquidchromatography，HPLC)测量尿液标本中甘露醇(mannitol，M)和乳果糖(lactulose，L)（不被代谢的糖分子）的排除率。M很容易吸收，可以作为一个跨细胞吸收标志，而L吸收很少，可以作为粘膜完整性标志。因此，尿样中L的排泄率与M的排泄率之比（L/M）可以用来衡量肠粘膜的通透性。与健康对照组相比，L/M值增加提示肠粘膜通透性增加。统计分析采用SPSS13.0软件。结果：总共46名儿童参与了本项研究：HSP组患儿26名，男孩16名，女孩10名，平均年龄6.04±1.75岁，平均体重22.38±2.63千克；健康对照组儿童20名，男孩13名，女孩7名，平均年龄6.23±2.12岁，平均体重23.49±3.24千克。两组儿童性别、年龄和体重无明显差异（p0.05）。HSP患儿粪便双歧杆菌数量和B/E值均低于对照组，差异有统计学意义（p0.05）。大肠杆菌数量两组比较，差异无统计学意义（p0.05）。HSP患儿粪便sIgA水平也低于对照组，差异有统计学意义（p0.05）。HSP患儿尿L%、L%和L/M值均明显高于对照组，差异有统计学意义（p0.05）。相关性分析显示：B/E值与粪便sIgA水平呈直线正相关关系，与L/M值呈直线负相关关系；L/M值与sIgA呈直线负相关关系。结论：HSP患儿双歧杆菌数量减少，B/E值减少，发生肠道菌群紊乱；同时，粪便sIgA水平降低，肠粘膜免疫状态改变；此外，L/M值增加，肠粘膜通透性增加。这些结果表明HSP患儿肠粘膜生物屏障、免疫屏障和机械屏障均受损。在HSP中B/E值、sIgA和L/M值分别两两相关，表明肠粘膜生物屏障、免疫屏障和机械屏障这三者之间也存在着复杂的相互作用，各自和协同参与了HSP的发生发展。本研究为在HSP早期保护肠粘膜屏障功能阻止疾病的发生发展提供理论依据。
[Abstract]:Objective : Henoch - Schonlein purpura ( HSP ) is an environment - mediated disease in which the immune system is involved , genetic susceptibility and environmental factors . Our study is expected to understand the complexity of this theory through the role of intestinal mucosal barrier function in the pathogenesis of HSP .

Methods : Twenty - six children ( mean age 6.04 卤 1.75 years old , 16 boys and 10 girls ) were collected from August 2011 to February 2012 at the Third Hospital of Hebei Medical University , and 20 children ( mean age , 6.23 卤 2.12 years , 13 boys and 7 girls ) in our hospital during the same period . HSP diagnosis refers to HSP diagnostic criteria developed by American College of Rheumatology in 1990 , that is , at least 2 requirements are met : the first onset age is not more than 20 years ;
obvious purpura ;
Acute abdominal pain ;
All selected children signed an informed consent form prior to the start of the study and agreed with the Ethics Committee of the Third Hospital of Hebei Medical University . feces and urine specimens were collected on the next day . The ratio of the number of Bifidobacterium and E . coli was analyzed by 16S rDNA fluorescence quantitative PCR . coli , B / E reflect intestinal microecological habitat . Compared with healthy control group , the decrease of B / E value suggested intestinal flora imbalance . The standard enzyme linked immunosorbent assay ( HPLC ) was used to measure the level of sIgA in stool .

Results : A total of 46 children participated in the study : 26 children in HSP group , 16 boys and 10 girls , the average age was 6.04 卤 1.75 years , the average body weight was 22.38 卤 2.63 kg ;
There was no significant difference between the two groups ( p < 0.05 ) . There was no significant difference between the two groups ( p < 0.05 ) . The levels of urine L % , L % and L / M in children with HSP were significantly higher than those in the control group ( p < 0.05 ) . The levels of urine L % , L % and L / M in children with HSP were significantly higher than those in the control group ( p < 0.05 ) .
There was a negative correlation between L / M and sIgA .

Conclusion : The number of B / E in children with HSP was decreased and B / E decreased , and intestinal flora was disturbed .
At the same time , the level of stool sIgA decreased and the mucosal immune status changed ;
The results showed that the intestinal mucosa biological barrier , immune barrier and mechanical barrier were all damaged in HSP children . In HSP , the B / E values , sIgA and L / M values were correlated with each other , indicating the complex interaction between the intestinal mucosa biological barrier , the immune barrier and the mechanical barrier . The study provided a theoretical basis for the early protection of intestinal mucosal barrier function in HSP .

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.5

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