Elzinga L, Kelley V E, Houghton D C, Bennett W M
Transplantation. 1987 Feb;43(2):271-4. doi: 10.1097/00007890-198702000-00021.
Cyclosporine-associated renal dysfunction is well recognized. While renal vasoconstriction appears to be a major pathogenic factor, the precise mechanism responsible for the altered hemodynamics is unclear. To investigate whether alterations in renal eicosanoid metabolism could be involved, we substituted fish oil rich in eicosapentaenoic acid (EPA), an inhibitor of cyclooxygenase metabolites, for the conventional olive oil cyclosporine vehicle. Male rats were pretreated with 1.0 cc fish oil or olive oil by gavage. After 14 days, cyclosporine (12.5 mg/cc vehicle) was added to the oil and animals received cyclosporine 50 mg/kg for an additional 14 days. Pair-fed control animals received fish oil or olive oil alone. Glomerular filtration rate (GFR) was severely reduced in the cyclosporine-in-olive-oil (CSA + OO) group (0.28 +/- .05 ml/min/100 g) vs. olive oil (OO) controls (0.70 +/- .04) (P less than 0.001). While GFR was reduced in the cyclosporine-in-fish oil group (CSA + FO) vs. fish oil (FO) controls (0.47 +/- .07 vs. 0.74 +/- .04), it was significantly higher than in the CSA + OO group (P less than 0.05). Trough whole-blood cyclosporine levels were not significantly different in the two groups. While CSA + OO appeared to elevate renal cortical content of thromboxane B2 (65.7 +/- 7.3 pg/mg tissue vs. 46.9 +/- 5.3 for OO), both the CSA + FO and FO groups had reduced levels (31.1 +/- 2.7 and 29.5 +/- 2.3, respectively). In addition, there was a striking reduction in proximal tubular vacuolar changes in the CSA +/- FO vs. CSA + OO group. We conclude that the use of EPA-rich fish oil as the vehicle for cyclosporine results in improved renal function and morphology and is associated with depressed renal cortical levels of vasoconstrictor thromboxane B2.
环孢素相关的肾功能障碍已得到充分认识。虽然肾血管收缩似乎是一个主要的致病因素，但导致血流动力学改变的确切机制尚不清楚。为了研究肾类花生酸代谢的改变是否与之有关，我们用富含二十碳五烯酸（EPA）的鱼油（一种环氧化酶代谢产物的抑制剂）替代了传统的橄榄油作为环孢素载体。雄性大鼠经口灌胃给予1.0 cc鱼油或橄榄油进行预处理。14天后，将环孢素（12.5 mg/cc载体）加入油中，动物再接受14天50 mg/kg的环孢素。配对喂养的对照动物仅接受鱼油或橄榄油。与橄榄油（OO）对照组（0.70±0.04）相比，橄榄油中环孢素组（CSA + OO）的肾小球滤过率（GFR）严重降低（0.28±0.05 ml/min/100 g）（P < 0.001）。与鱼油（FO）对照组相比，鱼油中环孢素组（CSA + FO）的GFR降低（0.47±0.07对0.74±0.04），但显著高于CSA + OO组（P < 0.05）。两组的谷值全血环孢素水平无显著差异。虽然CSA + OO似乎提高了肾皮质血栓素B2的含量（65.7±7.3 pg/mg组织，而OO为46.9±5.3），但CSA + FO组和FO组的水平均降低（分别为31.1±2.7和29.5±2.3）。此外，与CSA + OO组相比，CSA + FO组近端肾小管空泡变化显著减少。我们得出结论，使用富含EPA的鱼油作为环孢素载体可改善肾功能和形态，并与肾皮质血管收缩剂血栓素B2水平降低有关。
