Department of General Surgery, Clinical School of Nanjing, Second Military Medical University, Nanjing JingLing Hospital, Nanjing, China.
J Infect Dis. 2011 Jun 1;203(11):1602-12. doi: 10.1093/infdis/jir147.
This study aimed to examine the protective effect of berberine in endotoxin-induced intestinal tight-junction injury in a mice model of endotoxinemia.
Endotoxinemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Mice were randomized to 5 groups: control mice, berberine-treated mice, lipopolysaccharide (LPS)-injected mice, mice pretreated with berberine, and mice administered berberine following LPS injection. Samples were collected 12 h after LPS treatment.
Ileal mucosal permeability to fluorescein isothiocyanate dextran assay indicated that berberine reduced the permeability of the gut barrier in endotoxinemia. Transmission electron microscopy revealed that pretreatement with berberine partly prevented ultrastructural disruption of tight junctions by LPS. Immunofluorescence and Western blot analysis were performed, and the results demonstrated that pretreatement with berberine partially reversed the redistribution of tight-junction proteins in colon epithelium and in membrane microdomains. Our data also indicated that pretreatement with berberine could suppress translocation, from cytoplasm to the nucleus, of nuclear factor-κB and myosin light chain kinase activation in the intestinal epithelium.
Pretreatement with berberine attenuates disruption of tight junctions in intestinal epithelium in a mice model of endotoxinemia. This may possibly have been mediated through down-regulation of the nuclear factor-κB and myosin light chain kinase pathway.
本研究旨在探讨小檗碱对内毒素血症小鼠肠紧密连接损伤的保护作用。
通过腹腔注射脂多糖（10mg/kg）诱导内毒素血症。将小鼠随机分为 5 组：对照组、小檗碱处理组、脂多糖（LPS）注射组、小檗碱预处理组和 LPS 注射后给予小檗碱组。在 LPS 处理后 12 小时收集样本。
荧光素异硫氰酸酯右旋糖酐试验表明，小檗碱降低了内毒素血症时肠道屏障的通透性。透射电镜显示，小檗碱预处理部分阻止了 LPS 对紧密连接超微结构的破坏。免疫荧光和 Western blot 分析表明，小檗碱预处理部分逆转了结肠上皮和膜微区中紧密连接蛋白的重新分布。我们的数据还表明，小檗碱预处理可以抑制核因子-κB 的易位，从细胞质到细胞核，以及肌球蛋白轻链激酶在肠道上皮细胞中的激活。
小檗碱预处理可减轻内毒素血症小鼠肠上皮紧密连接的破坏。这可能是通过下调核因子-κB 和肌球蛋白轻链激酶通路来实现的。
