Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats
Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats
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DOI：
10.1016/s0002-9440(10)61196-0
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发表时间：
2005-10-01
影响因子：
6
通讯作者：
Bueno, L
中科院分区：
文献类型：
--
作者：
Moriez, R;Salvador-Cartier, C;Bueno, L
脓毒症与细菌易位(BT)和结肠旁细胞通透性(CPP)变化有关，但这些影响之间的联系尚不清楚。本研究旨在确定脂多糖(LPS)注射后CPP的变化是否会触发BT、结肠炎、内脏疼痛和疾病行为，并探讨肌球蛋白轻链激酶(MLCK)在结肠细胞细胞骨架收缩中的作用。大鼠接受MLCK抑制剂ML-7单独或与内毒素合用。给药后6h测定CPP。观察治疗后0~3h的内脏疼痛、进食量、BT、结肠细胞紧密连接的电子显微镜、细胞因子水平和结肠粘膜磷酸化MLC的Western blotting。脓毒症在内毒素后0~6小时升高CPP，并与紧密连接的形态改变、MLC磷酸化增加和粘膜促炎细胞因子的释放有关。还观察到大量的BT、内脏痛觉过敏和食物摄入量减少。添加ML-7可阻止内毒素诱导的所有效应，但改变食物摄入量。总之，内毒素对CPP的影响包括肠道炎症、BT和内脏痛觉过敏。ML-7抑制MLCK依赖的结肠细胞细胞骨架收缩可阻止内毒素引起的CPP改变及其后续效应。
Sepsis is associated with bacterial translocation (BT) and changes in colonic paracellular permeability (CPP), but the link between these effects is unknown. The present study aimed to identify whether changes in CPP after lipopolysaccharide (LPS) administration triggers BT, colonic inflammation, visceral pain, and sickness behavior and to evaluate the role of myosin light chain kinase (MLCK) in colonocyte cytoskeleton contraction. Rats received the MLCK inhibitor ML-7 alone or combined with LPS. CPP was measured for 6 hours after administration. Visceral pain, food intake, BT, electron microscopy of tight junctions of colonocytes, cytokine levels, and Western blotting of phosphorylated MLC from colonic mucosa were assessed in a time range of 0 to 3 hours after treatment. Sepsis increased CPP at 0 to 6 hours after LPS and associated with tight junction morphological changes, increased MLC phosphorylation, and mucosal release of proinflammatory cytokines. Massive BT, visceral hyperalgesia, and reduced food intake were also observed. Addition of ML-7 prevented all LPS-induced effects, except for changes in food intake. in conclusion, LPS-mediated effects on CPP include gut inflammation, BT, and visceral hyperalgesia. Inhibition of MLCK-dependent colonocyte cytoskeleton contraction by ML-7 prevents the LPS-induced alterations of CPP and its subsequent effects.