Dieperink H, Leyssac P P, Starklint H, Jørgensen K A, Kemp E
Eur J Clin Invest. 1986 Dec;16(6):540-8. doi: 10.1111/j.1365-2362.1986.tb02175.x.
Experimental evidence indicates that cyclosporin A (CyA) nephrotoxicity is due to renal arteriolar constriction, reducing renal blood flow, glomerular filtration rate (GFR), and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle. The proximal tubular fractional reabsorption (PFR) is increased. Therefore, the impact on renal function of vasodilating agents was studied in rats given CyA. Conscious catheterized rats and clearance techniques were used. In acute experiments a preexisting CyA-nephrotoxicity was resistant to infusion of phenoxybenzamine, prostacyclin, captopril, nifedipine and indomethacin. Concomitant treatment with captopril and CyA did not improve renal function, while concomitant treatment with CyA and nifedipine improved GFR to 1.13 +/- 0.34 ml min-1 g-1 kidney weight (gKW) (n = 19, P less than 0.05), as compared to CyA and placebo treated controls (n = 12, 0.83 +/- 0.32 ml min-1 g-1 KW). Nifedipine also reduced FPR (88.6 +/- 5.1% vs. 83.2 +/- 5.6%. P less than 0.01), and increased lithium clearance from 99 +/- 54 to 184 +/- 64 microliters min-1 g-1 KW (P less than 0.001). The results are further evidence that CyA nephrotoxicity includes renal vasoconstriction, and indicates that calcium entry blockade is nephroprotective in the case of CyA toxicity.
实验证据表明，环孢素A（CyA）肾毒性是由于肾小动脉收缩，导致肾血流量、肾小球滤过率（GFR）以及从近端小管末端到髓袢的肾小管液输送减少。近端小管分数重吸收（PFR）增加。因此，在给予CyA的大鼠中研究了血管扩张剂对肾功能的影响。使用清醒插管大鼠和清除技术。在急性实验中，预先存在的CyA肾毒性对苯氧苄胺、前列环素、卡托普利、硝苯地平和吲哚美辛的输注具有抗性。卡托普利与CyA联合治疗并未改善肾功能，而CyA与硝苯地平联合治疗可使GFR提高至1.13±0.34 ml·min⁻¹·g⁻¹肾重（gKW）（n = 19，P<0.05），相比之下，CyA与安慰剂治疗的对照组（n = 12，0.83±0.32 ml·min⁻¹·g⁻¹ KW）。硝苯地平还降低了FPR（88.6±5.1%对83.2±5.6%，P<0.01），并使锂清除率从99±54提高到184±64 μl·min⁻¹·g⁻¹ KW（P<0.001）。这些结果进一步证明CyA肾毒性包括肾血管收缩，并表明钙内流阻滞在CyA毒性情况下具有肾保护作用。
