普伐他汀对脑卒中易感型自发性高血压大鼠脑损害及内皮细胞功能的影响

Effect of pravastatin on the cerebral damage and the endothelial function in stroke-prone spontaneous hypertensive rats

目的 了解普伐他汀对脑卒中易感型自发性高血压大鼠 (SHRsp)的脑损害的预防作用 ,并探讨其机制。方法 (1)整体动物实验 :将 2 2只 7周龄SHRsp随机分为普伐他汀 (2 0mg·kg- 1 ·d- 1 )治疗组和对照组 ,灌胃治疗 8周 ,离取各组大鼠脑组织和颈动脉 ,分别进行透射电镜和扫描电镜检查。还检查了血压、血脂和血液循环内皮细胞(CEC)计数。 (2 )内皮细胞培养部分 :胎儿脐静脉内皮细胞经 0、1、2、5、15 μmol L不同浓度的普伐他汀作用 72h后 ,收取培养液。用Griess法测定一氧化氮 (NO)代谢产物亚硝酸盐的浓度。结果 (1)整体动物实验 :治疗 8周 ,治疗组血压、血脂与对照组比较无明显差异。但在电镜下已观察到 :对照组颈动脉内皮细胞出现肿胀和脱失现象 ;神经细胞出现核固缩、线粒体肿胀和内质网扩张等病理改变。而治疗组颈动脉内膜和神经细胞形态病理改变不明显。治疗组CEC计数较对照组低 2 2 % [治疗组 (19.11± 5 .0 6 )个 mm3;对照组 (2 4 .5 0± 4 .90 )个 mm3,P =0 .0 2 6 ]。 (2 )内皮细胞培养部分 :经 0 ,1、2、5、15 μmol L不同浓度的普伐他汀作用 72h后 ,培养液中NO亚硝酸盐代谢产物浓度分别为 6 .99,6 .88、7.85、10 .5 7和 8.0 5 μmol L。结论 普伐他汀能够预防SHRsp脑损害的发生。该作用?

Objective To investigate the effect of pravastatin on the cerebral damage in stroke prone spontaneous hypertensive rat (SHRsp) and its related mechanisms.Methods (1)Animal experiment: Twenty two SHRsp were randomized into active treatment (pravastatin 20 mg·kg -1 ·d -1 )group and control group.After 8 weeks,transmission electron microscopy(TEM) or scanning electron microscopy(SEM) was carried out respectively to evaluate the ultrastructure changes of neurocytes and carotid endothelium in each group. Additionally, tail blood pressure, serum lipids levels and the numbers of circulating endothelial cells were determined for each group.(2)Endothelial cell culture: Human umbilical vein endothelial cells were cultured in the growth mediums containing 0?1?2?5?15 μmol/L pravastatin respectively for 72 hours.Then the mediums were collected for the measurement of NO concentration using the Griess Method.Results (1)Animal experiment:After 8 weeks, the levels of lipids and tail blood pressure showed no differences between two groups. But there were obviously pathologic ultrastructure changes of carotid endothelial cells and neurocytes, such as neuronal karyopyknosis, endoplasmic reticulum dilation, mitochondria swelling and endothelium detachment in the control group. The number of circulating endothelial cells of active treatment group were 22% lower than that of control group (19.1±5.06/mm 3 vs 24.50±4.90/mm 3;P=0.026), which was accordant with the SEM result.(2)Endothelial cell culture:Thes were 6.99 ,6.88,7.85,10.57 and 8.05 μmol/L respectively when the pravastatin concentrations in the growth mediums were 0, 1,2,5 and 15 μmol/L.Conclusions Pravastatin can effectively prevent the cerebral damage of SHRsp.The neuroprotective effects of pravastatins may be partly due to increasing the endothelial NO biosynthesis.