中文摘要：

紧密连接紊乱在多种慢性病病理过程中发挥重要作用，也是金属药物（如抗糖尿病钒化合物）临床应用的一个主要问题。寻找紧密连接保护性药物是目前一个努力的工作方向。因钒化合物主要通过氧化应激损伤而产生肾毒性，我们在MDCK细胞单层模型上研究了葡萄糖酸锌，维生素C以及两者联合用药对钒化合物引起的细胞旁通路通透性增加的作用。结果表明，VO（acac）2导致细胞旁通路通透性明显增加。单独使用葡萄糖酸锌没有保护作用；当在底侧给予维生素C时，能够抑制MDcK细胞紧密连接的打开。而在任意单侧同时加入锌和维生素C则能够有效阻止紧密连接通透性的增加。研究发现，维生索C与锌联用存对照组与VO（acac）2作用组中，都能够下调细胞氧化应激水平，并引起细胞内钙的升高。这两种效果部有利于细胞单层紧密连接的完整性维持。实验结果为预防抗糖尿病钒化合物的金属毒性提供了一种简单而日．有效的方法。

英文摘要：

The tight junction disorder plays an important role in the pathological process of many chronic diseases, and is becoming a major concern for the clinical application of metal drugs, i.e. anti-diabetic vanadium compounds. The development of novel tight junction protecting agents has thus been a major research focus. Since oxidative stress is the primary cause for vanadium toxicity, the present work tested the protective effects of zinc gluconate （Zn2＋） alone and when combined with vitamin C （VC） on the vanadium compound （VO（acac）z.）-mediated paracellular leakage of MDCK cells. The experimental results showed that VO（acac）2_ treatment significantly increased the paracellular permeability of MDCK monolayer. Zn2＋ alone showed no protective effects and VC ameliorated tight junction leakage of MDCK cells when given in the basal chamber. Interestingly, unilateral treatment with the combination of Zn2＋ and VC effectively prevented the increase of paracellular permeability. In addition, the combination of zinc and VC down-regulated the levels of reactive oxygen species in both the control and VO（acac）2-treated MDCK cells and caused the elevation of intracellular Ca2＋; both effects were beneficial for the maintenance of integrity of intercellular tight junction. Our results provided a simple but very effective method of preventing the metal toxicity for clinical aoNication of anti-diabetic vanadium compounds.