不同剂量匹伐他汀对小鼠缺血肢血流恢复的影响

Effect of different dosages of pitavastatin on blood flow recovery in ischemic limbs of mice

目的探讨不同剂量匹伐他汀对小鼠缺血肢血流恢复的影响,为临床应用合适剂量他汀类药物提供实验依据。方法建立小鼠下肢缺血模型并分为对照组、匹伐他汀低剂量组及高剂量组。镉还原Griess法、生化检测法测定3组实验结束后血清一氧化氮代谢产物及肝肾功能等含量。激光多普勒血流仪测定3组投药前及术后双下肢血流。蛋白印迹杂交法检测各组双下肢血管内皮生长因子(VEGF)蛋白表达。结果低剂量组实验结束后肝肾功能无明显变化,一氧化氮代谢产物明显高于另外2组,术后缺血肢血流恢复明显,缺血肢VEGF蛋白表达增强。高剂量组肾功能损伤明显高于对照组和低剂量组,一氧化氮代谢产物明显低于低剂量组,术后缺血肢血流恢复不明显,缺血肢VEGF蛋白表达低于低剂量组。结论低剂量匹伐他汀促进了小鼠缺血肢血流的恢复。

Objective： To investigate the effect of different dosages of pitavastatin on the blood flow recovery in the ischemic limbs of mice and thus provide evidences for selecting optimal dosage of pitavastatin in clinical practice, Methods ：The mice models of isehemie hind limbs were established and divided into 3 groups： control group, low-dosage pitavastatin group, and high-dosage pitavastatin group, The blood flow of hind limbs both before administration of pitavastatin and after ischemia was measured by laser Doppler flowmetry. The serum levels of the metabolites of nitric oxide （NO） and the liver and kidney functions were determined by Gfiess technique and biochemical technique, respectively. The expression of vascular endothelial growth factor （VEGF） was detected by Western blotting. Results： Compared with control group and high-dosage pitavastatin group, the liver and kidney functions did not change obviously, the NOx level was significantly higher, the blood flow recovered obviously, and the expression of VEGF increased in the low-dosage pitavastatin group, Conclusion：Low-dosage provastatin promotes the blood flow recovery of the ischemic limbs in mice.