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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,维生素C与锌联用在对照组与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。这两种效果都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且有效的方法。
Tight junctions play an important role in the pathogenesis of a variety of chronic diseases and are also a major problem for the clinical use of metal drugs such as anti-diabetic vanadium compounds. Looking for close connection with protective drugs is a hard work direction. Since vanadium compounds are primarily nephrotoxic to oxidative stress, we investigated the effect of zinc gluconate, vitamin C, and a combination of these two agents on the increase of paracellular permeability caused by vanadium compounds on the MDCK monolayer model. The results showed that VO (acac) 2 led to a significant increase of paracellular permeability. Zinc gluconate alone had no protective effect; when vitamin C was administered on the basal side, it was possible to inhibit the opening of tight junctions of MDCK cells. Adding zinc and vitamin C at any one side can effectively prevent the tight junction from increasing. The study found that vitamin C combined with zinc in the control group and VO (acac) 2 role group, are able to down-regulate the level of cellular oxidative stress and cause intracellular calcium. Both of these effects contribute to the integrity maintenance of tight junctions of cell monolayers. The experimental results provide a simple and effective method for preventing the metal toxicity of anti-diabetic vanadium compounds.