Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum
Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum
复制标题
DOI：
10.1136/gut.2006.100198
复制
发表时间：
2007-03-01
期刊：
影响因子：
24.5
通讯作者：
Schulzke, Joerg-Dieter
中科院分区：
文献类型：
--
作者：
Troeger, Hanno;Epple, Hans-Joerg;Schulzke, Joerg-Dieter
背景资料：贾第鞭毛虫引起小肠感染，导致吸收不良和慢性腹泻，目的：探讨贾第鞭毛虫感染的内在病理机制，方法：对13例慢性贾第鞭毛虫病患者和对照组的十二指肠活检标本进行内镜检查。短路电流（ISC）和甘露醇通量测定在dumberised的Ussing室。通过阻抗谱测定上皮和上皮下电阻。进行粘液形态测定，并通过免疫印迹法对紧密连接蛋白进行表征。凋亡率测定末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记staining.Results：在贾第虫病，粘膜表面积每单位浆膜面积减少到75%（3%）的控制，作为一个结果，上皮电阻应增加。相反，贾第虫病活检标本的上皮电阻降低（19（2）对25（2）Ω cm（2）; p <0.05），而甘露醇流量没有显著改变（140（27）对105（16）nmol/h/cm（2））。作为结构相关性，检测到减少的claudin 1表达和增加的上皮细胞凋亡。此外，基础ISC从对照组的191（20）mA/h/cm（2）增加到贾第虫病组的261（12）mA/h/cm（2）。贾第虫病患者ISC的布美他尼敏感部分也增加（51（5）vs 20（9）mA/h/cm（2）; p <0.05）。最后，贾第虫病患者根皮苷敏感性Na +-葡萄糖共输减少（121（9）vs 83（14）mA/h/cm（2））。结论：由于紧密连接蛋白claudin 1下调和上皮细胞凋亡增加，G lamblia感染导致上皮细胞屏障功能障碍。Na+依赖性D-葡萄糖吸收受损，活性产电阴离子分泌被激活。因此，人类慢性贾第虫病的腹泻机制包括漏流、吸收不良和分泌成分。
Background: Giardia lamblia causes infection of the small intestine, which leads to malabsorption and chronic diarrhoea.Aim: To characterise the inherent pathomechanisms of G lamblia infection.Methods: Duodenal biopsy specimens from 13 patients with chronic giardiasis and from controls were obtained endoscopically. Short-circuit current (ISC) and mannitol fluxes were measured in miniaturised Ussing chambers. Epithelial and subepithelial resistances were determined by impedance spectroscopy. Mucosal morphometry was performed and tight junction proteins were characterised by immunoblotting. Apoptotic ratio was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining.Results: In giardiasis, mucosal surface area per unit serosa area was decreased to 75% (3%) of control, as a result of which epithelial resistance should increase. Instead, epithelial resistance of giardiasis biopsy specimens was decreased ( 19 ( 2) vs 25 ( 2) Omega cm(2); p < 0.05) whereas mannitol flux was not significantly altered ( 140 ( 27) vs 105 ( 16) nmol/h/cm(2)). As structural correlate, reduced claudin 1 expression and increased epithelial apoptosis were detected. Furthermore, basal ISC increased from 191 ( 20) in control to 261 ( 12) mA/h/cm(2) in giardiasis. The bumetanide-sensitive portion of ISC in giardiasis was also increased ( 51 ( 5) vs 20 ( 9) mA/h/cm(2) in control; p < 0.05). Finally, phlorizin-sensitive Na+-glucose symport was reduced in patients with giardiasis ( 121 ( 9) vs 83 ( 14) mA/h/cm(2)).Conclusions: G lamblia infection causes epithelial barrier dysfunction owing to down regulation of the tight junction protein claudin 1 and increased epithelial apoptoses. Na+-dependent D-glucose absorption is impaired and active electrogenic anion secretion is activated. Thus, the mechanisms of diarrhoea in human chronic giardiasis comprise leak flux, malabsorptive and secretory components.