Tsuchiya Atsushi, Nagotani Shoko, Hayashi Takeshi, Deguchi Kentaro, Sehara Yoshihide, Yamashita Toru, Zhang HanZhe, Lukic Violeta, Kamiya Tatsushi, Abe Koji
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmacy, Okayama University, Japan.
Curr Neurovasc Res. 2007 Nov;4(4):268-73. doi: 10.2174/156720207782446333.
Statin reduces cerebrovascular events independent of its cholesterol lowering effect. We hypothesized that statin inhibits early atherosclerotic change in common carotid artery (CCA), and investigated its effect on lectin-like oxidized-LDL receptor-1 (LOX-1) and monocyte chemoattractant protein-1 (MCP-1) expression, both of which are early atherosclerotic markers. Stroke-prone spontaneous hypertensive rats (SHR-SP) of 8 weeks old were orally treated with vehicle or simvastatin (20mg/kg) daily. After 4 weeks of simvastatin or vehicle treatment, or 2 weeks of vehicle and 2 weeks of simvastatin treatment, CCA was removed. LOX-1 and MCP-1 expression as well as macrophage infiltration were histologically investigated. Lipid deposition was also investigated by Sudan III staining. Simvastatin groups showed significantly smaller amount of lipid deposition and LOX-1 and MCP-1 expression, independent of serum lipid levels. Macrophage infiltration was also decreased. Reduction of cerebrovascular events by statins may be brought by the direct inhibition of atherosclerotic change.
他汀类药物可独立于其降胆固醇作用而降低脑血管事件的发生风险。我们推测他汀类药物可抑制颈总动脉（CCA）早期动脉粥样硬化改变，并研究了其对凝集素样氧化低密度脂蛋白受体-1（LOX-1）和单核细胞趋化蛋白-1（MCP-1）表达的影响，这两者均为早期动脉粥样硬化标志物。对8周龄的易卒中型自发性高血压大鼠（SHR-SP）每日口服赋形剂或辛伐他汀（20mg/kg）。在辛伐他汀或赋形剂治疗4周后，或赋形剂治疗2周后再进行2周辛伐他汀治疗后，取出颈总动脉。对LOX-1和MCP-1表达以及巨噬细胞浸润进行组织学研究。还通过苏丹III染色研究脂质沉积情况。辛伐他汀组脂质沉积量以及LOX-1和MCP-1表达均显著减少，且与血脂水平无关。巨噬细胞浸润也减少。他汀类药物降低脑血管事件的发生风险可能是通过直接抑制动脉粥样硬化改变实现的。
