Inman Sharon R, Davis Nancy A, Olson Kristen M, Lukaszek Victoria A
College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Am J Med Sci. 2003 Sep;326(3):117-21. doi: 10.1097/00000441-200309000-00002.
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors increase renal blood flow independent of their lipid-lowering properties. In organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its renal vasoconstrictor properties limit its use. This study aimed to determine the effect of an HMG-CoA reductase inhibitor, simvastatin (Zocor), on renal function in rats after ischemia/reperfusion injury (I/R) with concomitant CyA treatment.
Male Wistar rats (250 g) were anesthetized and the suprarenal aorta clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into 5 groups: (1) control rats, no ischemia, no treatment; (2) ischemia with no treatment; (3) ischemia plus CyA only; (4) ischemia plus CyA and low-dose simvastatin; and (5) ischemia plus CyA and high-dose simvastatin. Five to 7 days after I/R injury, glomerular filtration rate (GFR) was determined using urinary iohexol clearance.
The GFR values (mL/min) for all 5 groups were as follows: (1) 1.23 +/- 0.08; (2) 1.05 +/- 0.10; (3) 0.44 +/- 0.06 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); (4) 0.51 +/- 0.04 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); and (5) 0.85 +/- 0.11.
After I/R injury and cyclosporine treatment, simvastatin preserved renal function compared with cyclosporine treatment alone because it may not have a direct vasoconstrictor effect on the renal microcirculation. In fact, it may exhibit vasodilator properties on the renal microcirculation mediated by nitric oxide.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂可增加肾血流量，且与它们的降脂特性无关。在器官移植中，钙调神经磷酸酶抑制剂环孢素A（CyA）是首选的免疫抑制剂。然而，其肾血管收缩特性限制了它的应用。本研究旨在确定HMG-CoA还原酶抑制剂辛伐他汀（舒降之）对伴有CyA治疗的缺血/再灌注损伤（I/R）大鼠肾功能的影响。
将雄性Wistar大鼠（250克）麻醉，夹闭肾上腹主动脉40分钟。切除右肾。恢复后，将大鼠分为5组：（1）对照大鼠，无缺血，未治疗；（2）缺血未治疗；（3）缺血加CyA；（4）缺血加CyA和低剂量辛伐他汀；（5）缺血加CyA和高剂量辛伐他汀。I/R损伤后5至7天，使用尿碘海醇清除率测定肾小球滤过率（GFR）。
所有5组的GFR值（毫升/分钟）如下：（1）1.23±0.08；（2）1.05±0.10；（3）0.44±0.06（与第1、2和5组相比，P<0.05；单因素方差分析）；（4）0.51±0.04（与第1、2和5组相比，P<0.05；单因素方差分析）；（5）0.85±0.11。
在I/R损伤和环孢素治疗后，与单独使用环孢素治疗相比，辛伐他汀可保护肾功能，因为它可能对肾微循环没有直接的血管收缩作用。事实上，它可能通过一氧化氮介导对肾微循环表现出血管舒张特性。
