HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats

被引:98
作者
Kawashima, S [1 ]
Yamashita, T [1 ]
Miwa, Y [1 ]
Ozaki, M [1 ]
Namiki, M [1 ]
Hirase, T [1 ]
Inoue, N [1 ]
Hirata, K [1 ]
Yokoyama, M [1 ]
机构
[1] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Cardiovasc & Resp Med,Chuo Ku, Kobe, Hyogo 6500017, Japan
关键词
mortality; rats; inbred SHR; statins; stroke; superoxides;
D O I
10.1161/01.STR.0000048213.18751.52
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle cerebral artery, statins were shown to reduce infarct size. However, the effect of statins on hypertension-based stroke is unknown. The purpose of this study is to clarify the effect of a statin on stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both cerebral hemorrhage and infarction occur. Methods-We treated SHR-SP chronically from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle. The physiological parameters, the incidence of stroke-associated symptoms, and mortality were assessed. Results-At 14 weeks of age, the incidence (13 +/- 3% versus 37 +/- 8%; P<0.01) and the size of stroke (1.6 +/- 0.2 versus 2.2 +/- 0.1 arbitrary units; P<0.01) were significantly decreased by cerivastatin, although blood pressure and plasma cholesterol levels were not different. Moreover, stroke-associated symptoms and early mortality of SHR-SP were markedly reduced in the statin-treated group (mortality at the age of 15 weeks: 15% versus 50%; P<0.05). Statin treatment significantly reduced superoxide production from nonstroke parenchyma of brain and infiltration of inflammatory cells to the stroke lesions. Conclusions-Our data show that a high dose of statin exerts protection against hypertension-based stroke and ameliorates the disease severity via inhibition of superoxide production and modulation of inflammation in brain.
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页码:157 / 163
页数:7
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