肝门阻断对肝硬化大鼠肠黏膜屏障的影响

Effects of pringle maneuver on intestinal barrier function in liver cirrhotic rats

目的探讨肝硬化大鼠肝门阻断后肠道黏膜屏障结构和功能的改变。方法 40只肝硬化模型雄性SD大鼠被随机分为假手术组、肝门阻断10min、肝门阻断20min、肝门阻断30min组,每组各10只。在行肝门阻断术后18h乳果糖、甘露醇混合液灌胃,6h后收集尿液,检测乳果糖和甘露醇排出率及比值(L/M),并于术后24h取未段回肠行病理组织学和电镜检查。结果肝硬化大鼠肝门阻断10min时即出现明显小肠病理损伤,电镜下可见小肠微绒毛肿胀、缩短,紧密连结变宽。阻断20min时,小肠微绒毛缺失、脱落,细胞器肿胀。阻断30min时,可见部分肠黏膜细胞坏死,微绒毛脱落以及紧密连结破坏。肝门阻断10min组大鼠的尿中L/M比值(0.069±0.022)明显高于假手术组(0.047±0.016),并随肝门阻断时间延长增高越明显。结论肝硬化大鼠肝门阻断后可导制肠道黏膜通透性增加,肠黏膜屏障功能受损。

Objective To investigate the effects of pringle manoeuver（Pm） on intestinal barrier function in cirrhotic rats. Methods A total of 40 male SD liver cirrhotic rats was randomly divided into four equal groups： sham operation （n = 10）, Pm of 10 min （n = 10）, Pm of 20 min （n = 10） and Pm of 30 min （n = 10） respectively. All the animals were gavaged with lactulose and mannitol 18 hours after the operation. The urine of next 6 hours was collected and the ratio of the two sugars＇ percentage （L/M） ratio was measured to test the intestinal permeability. The distal ileum was collected for histological and electron microscopy examination 24 hours after the operation. Results Histological examination showed that the pathological damage of small intestine significantly increased in Pm of 10 min group. Electron microscopy examination showed that the microvillis became edema, shorter and the tight junctions became wider in Pm of 10 min group. While in Pm of 20 min group, the microvillis disruption and loss were noted, and the cellular organelle became swollen. In Pm of 30 min group, it was noted that many of the mucosal villi contained necrotic cells, the microvillis desquamated and the tight junctions were destroyed. The L/M ratio of the urine in Pm of 10 min group （0.069 ± 0.022） was significantly higher than that in sham operation group （0.047± 0.016）, and the L/M ratio increased with prolongation of pringle maneuver. Conclusion Occlusion of the hepatoduodenal ligament results in an increase of intestinal permeability and damages of the intestinal barrier function in cirrhotic rats.