肠屏障功能对豚鼠胆囊胆色素结石形成的影响

Influence of intestinal barrier function on pigment gallstone formation in guinea pig model

目的:探讨肠屏障功能与胆色素结石形成间的相关性,及其可能的作用机制.方法:豚鼠80只随机分为对照组(CON)、成石组(PS)、肠黏膜保护组(GLN),分别给予正常饲料、胆色素结石致石饮食、添加肠黏膜保护剂谷氨酰胺的致石饮食,饲养8wk建立胆囊胆色素结石模型.检测并比较各组胆结石成石率、肠黏膜形态、肠黏膜通透性、血浆内毒素水平、胆汁β-葡萄糖醛酸酶活性.结果:成石组成石率为73.9%,与正常组相比,成石组肠黏膜通透性增加,肠黏膜细胞超微结构受损,血浆内毒素水平[由(77±43)×10-6EU/L增至(1367±525)×10-6EU/L,P<0.01]和内、外源性胆汁β-葡萄糖醛酸酶活性增高(内源性由122.1±39.5Fishman单位增至209.8±47.5Fishman单位,P<0.01,外源性由573.5±476.9Fishman单位增至2206.6±983.9Fishman单位,P<0.01).肠黏膜保护组成石率下降至44.4%,各指标均较成石组降低,内毒素水平[(156±97)×10-6EU/Lvs(1367±525)×10-6EU/L,P<0.05]、肠黏膜通透性、肠黏膜细胞受损程度均较成石组有显著性差异,而胆汁β-葡萄糖醛酸酶活性无显著差异.结论:胆色素结石与肠屏障功能异常之间具有一定的相关性.肠屏障功能异常可能通过继发细菌移位、内毒素血症、胆汁β-葡萄糖醛酸酶活性改变,在促进胆色素结石的形成中发挥一定的作用.

AIM： To investigate the possible action and mechanism of the intestinal barrier function in the pathogenesis of pigment gallstone. METHODS： Eighty guinea pigs were randomly divided into three groups： normal group （CON）, pigment gallstone group （PS） and intestinal mucosa protection group （GLN）. Normal forage, pigment gallstone-forming forage and pigment gallstone-forming forage with supplemental intestinal mucosa protector （glutamine） were given to the animals of corresponding groups, respectively. The gallstoneforming rate, morphological changes of intestinal mucosa, intestinal permeability, serum endotoxin and biliary β-glucuronidase were detected after 8 wk. RESULTS： The gallstone-forming rate was 73.9% in PS. In comparison with those in CON, the intestinal mucosa damage, serum endotoxin level [（1367±525） ×10^-6 EU/L vs （77±43） ×10^-6 EU/L, P 〈 0.01] and activity of biliary β-glucuronidase （endogenous： from 209.8±47.5 vs 122.1±39.5 Fishman Unit, P 〈 0.01; exogenous： from 2206.6±983,9 vs 573.5±476.9 Fishman Unit,P 〈 0.01） were significantly increased in PS. In GLN, the gallstone-forming rate was decreased to 44.4%, which was markedly higher than that in PS （P 〈0.05）. The morphological changes of intestinal mucosa, intestinal permeability and serum endotoxin [（156±97）×10^-6 EU/L vs （1367±525）×10^-6 EU/L, P 〈0.05] were notably decreased in GLN as compared with those in PS, and there was no significant differ- ence in β-glucuronidase activity. CONCLUSION： Intestinal barrier function is correlated with pigment gallstone formation. Intestinal barrier function disorder may promote pigment gallstone formation through bacteria translocation, endotoxemia and change of biliary β-glucuronidase activity.