The Role of Protein Kinase C in Kidney Toxicity by New Immunosuppressant

FK-506具有与环孢菌素A极其相似的免疫调控作用。近年来，对免疫调控机制的研究日益深入。如果FK-506进入T细胞，它会与FK-506结合蛋白免疫亲和素结合。认为FK-506-免疫亲和素复合体通过钙离子和钙调蛋白抑制钙调神经磷酸酶，控制T细胞功能，发挥免疫调控作用。然而，在很多情况下，该药存在肾毒性问题，因为有效血液中的浓度与副作用区域的浓度特别接近。在此基础上，采用SD大鼠的方法，观察蛋白激酶C(PKC)在肾脏组织中的参与情况，具体为对照组大鼠肾脏屠宰后立即腹腔注射FK-506组(2.5m g/g体重组、5.0m g/g体重组)，并将其分为肾皮质和肾M…。冰面上有更多的箭。然后，测定并比较各组织提取液的PKC活性，以Bmax(PKC总量)和Kd(分离常数)作为各组织提取液的磷脂受体。目前，FK-506(5.0 mg/g体重)给药组的Bmax(总PKC)有低于对照组的趋势，但无显著差异。FK-506腹腔给药组与对照组相比，PKC活性无明显差异。考虑到这些原因，有可能是FK-506用药量不足或作用机制与环孢素A不同。此外，目前已证实PKC至少有7种同工酶，所以FK-506药物并不总是改变所有同工酶，而只改变某些同工酶，我们将继续这方面的研究。我们可能需要通过层析分离PKC同工酶来进行实验。较少

FK-506 does the extremely similar action of immunity control as cyclosporine A. Recently, the research on the mechanism of immunity control has advanced increasingly. If FK-506 enters T-cell, it will combine with FK-506-binding protein, immunophilin. It is thought that this FK-506-immunophilin complex impedes calcineurin by Ca++ and calmodulin, and that it controls the function of T-cell and demonstrates the action of immunity control. However, this medicine poses problems about the kidney toxicity in many cases, because the concentration in effective blood and the one in side-effects region are especially close. And then, we examine the possibility of participation of proteinkinaseC (PKC) in kidney organization, with SD-rat.Specifically, we extract FK-506 medication groups in the abdominal cavity (2.5 mg/g weight medication group, 5.0 mg/g weight medication group) immediately after slaughtering the kidney of the contrast medication group, and divid them into kidney cortex and kidney m … More arrow on the ice. Then, we measure and compare PKC activity of extracted liquid of each organization, Bmax (total amount of PKC) and Kd(separative constant) as the phorbolester receptor of each organization extracted liquid. At present, Bmax (total amount of PKC) of FK-506 (5.0mg/g weight) medication group shows lower tendency than a contrast group, but it is not significant difference. As for PKC activity, there is no difference between FK-506 medication groups in the abdominal cavity and contrast groups. Considering about causes of these, there are possibilities such as the lack of the amount of FK-506 medication or the difference of the action mechanism from cyclosporine A. Besides, at present, it is confirmed that PKC has at least seven kinds of isozymes, so that FK-506 medication does not always make change in all kinds of isozymes but makes change only in some kinds of isozyme.We will continue this research, furthermore. We possibly need to experiment by dividing PKC isozyme with chromatography. Less