Duggin G G, Baxter C, Hall B M, Horvath J S, Tiller D J
Clin Nephrol. 1986;25 Suppl 1:S43-5.
In the acute clinical situation, CSA produces reversible renal impairment. Studies by Morris et al. [1982] and others indicate that this is rapidly reversible when the drug is ceased. A series of studies have been performed in rats with the aim of examining changes in GFR, together with changes in the intrarenal renin-angiotensin system and renal release of prostaglandins. Rats were treated for 3-7 days with CSA and at the end of the experiment kidneys were removed and renal cortical slices prepared. There was increased renin secretion from the CSA-treated rats, compared to controls, and the response was dose-dependent. There was an increase in renal cortical renin content paralleling the renin release. Determinations of plasma renin in these animals also indicated a rise in plasma renin activity associated with time. In animals not pretreated with CSA, the renal cortical slices incubated with CSA demonstrated a stimulation of renin release. A further group of rats pretreated with 100 mg/kg/day of CSA for 3-7 days showed no change in renal slice release of 6-keto-PGF1 alpha, thromboxane B2, PGE2 and PGF2 alpha. This data indicates that the renal renin-angiotensin system is activated by CSA and produces a dissociation of the linkage between renal slice prostaglandin release and the renin angiotensin system. This would indicate that CSA affects the intrarenal control of GFR. However, the exact site of the modulation remains to be determined.
在急性临床情况下，环孢素A（CSA）会导致可逆性肾功能损害。莫里斯等人[1982年]及其他研究表明，停药后这种损害可迅速逆转。为了研究肾小球滤过率（GFR）的变化，以及肾内肾素 - 血管紧张素系统和肾脏前列腺素释放的变化，已在大鼠身上进行了一系列研究。用CSA对大鼠进行3 - 7天的治疗，实验结束时取出肾脏并制备肾皮质切片。与对照组相比，CSA治疗的大鼠肾素分泌增加，且反应呈剂量依赖性。肾皮质肾素含量的增加与肾素释放平行。对这些动物血浆肾素的测定也表明，血浆肾素活性随时间升高。在未用CSA预处理的动物中，用CSA孵育的肾皮质切片显示肾素释放受到刺激。另一组以100mg/kg/天的CSA预处理3 - 7天的大鼠，其肾切片中6 - 酮 - PGF1α、血栓素B2、PGE2和PGF2α的释放没有变化。这些数据表明，CSA激活了肾内肾素 - 血管紧张素系统，并导致肾切片前列腺素释放与肾素 - 血管紧张素系统之间的联系解离。这表明CSA影响了GFR的肾内调节。然而，调节的确切部位仍有待确定。
