西洛他唑改善脑梗死急性期小鼠脑血流量作用机制研究

Effect of cilostazol on cerebral blood flow after ischemic stroke

目的观察西洛他唑(CLZ)改善脑梗死急性期小鼠脑血流量的效果并探讨其作用机制。方法12只8周龄雄性Icr小鼠建立左侧大脑中动脉永久闭塞模型,分为CLZ组、PBS组及HPβCD组,每组4只,给予CLZ悬浊液、PBS溶液及HPβCD溶液后于不同时间点进行ROI区域(L)及对侧映射区域(R)的脑血流量测定。另将CLZ、PBS和HPβCD分别加入培养液中对小鼠大脑由来血管内皮细胞进行培养,6d后采用Western blot法检测细胞磷酸化内皮型一氧化氮合成酶(p-eNOS)及内皮型一氧化氮合成酶含量(e NOS)并对比分析。结果CLZ组小鼠注射药物后半暗带区域脑血流量较其他两组小鼠有所增加;注射后20、30及60min时的L/R比值均高于0min,且注射后20、30min时的L/R比值均高于PBS组、HPβCD组,差异均有统计学意义(均P<0.05)。结论CLZ可改善脑梗死急性期梗死区域脑血流量,其作用机制可能为促进p-eNOS活性的表达。

Objective To investigate the effect of cilostazol(CLZ)on cerebral blood flow after acute cerebral infarction in mice.and the effect of phospho-eNOS(p-e NOS)expression.Methods Permanent focal cerebral ischemia was induced by ligation and disconnection of the distal portion of the left middle cerebral artery(L-MCA)in 12 male Icr mice of 8-week-old.The ischemic mice were treated with CLZ,PBS and PBS group and HPβCD,respectively.The cerebral blood flow(CBF)was determined by laser speckle flowmetry.The cultured endothelial cells derived from rat brain(ECs)were treated with CLZ,PBS and HPβCD,the p-eNOS and eNOS were detected by Western blot after 6 d.Results There was significant difference in the CBF between 50μl CLZ group and PBS grop,HPβCD group(P<0.05).The ratio of p-eNOS/t-eNOS in ECs cultured with CLZ was significantly different with ECs treated with PBS and HPβCD.Conclusion Results indicate that CLZ can improve the microcirculation in post-ischemic region of brain through upregulation of e NOS activity in rats.