摘要
目的研究非诺贝特(fenofibrate,Fen)对小鼠急性局灶性脑缺血再灌注损伤的保护作用及机制。方法线栓法制备小鼠大脑中动脉栓塞模型,缺血90 min后再灌注。非诺贝特(10,80 mg.kg-1)再灌注同时及再灌后2 h各灌胃给药1次。再灌注后24 h,测定小鼠神经功能缺失评分、脑梗死体积及脑水肿程度,实时逆转录多聚酶链反应(RT-PCR)法检测过氧化物酶体增殖物激活受体α(PPARα)mRNA的表达水平,生化法测定脑组织丙二醛(maiondialdehyde,MDA)含量及超氧化物歧化酶(superoxide dismutase,SOD)的活性,伊文思蓝(Evans blue,EB)法观察血脑屏障破坏程度;应用过氧化物酶体增殖物激活受体α拮抗剂MK886(10 mg.kg-1),观察过氧化物酶体增殖物激活受体α是否参与非诺贝特的脑保护作用。结果非诺贝特(80 mg.kg-1)可改善小鼠神经功能缺失,减小脑梗死体积,减轻脑水肿程度,减少脑缺血后脑内伊文思蓝的渗漏,上调脑损伤后脑内过氧化物酶体增殖物激活受体αmRNA的表达,减轻脑组织的脂质过氧化。MK886可拮抗非诺贝特的保护作用。结论非诺贝特可通过上调过氧化物酶体增殖物激活受体αmRNA表达、减轻脂质过氧化损伤而对小鼠急性局灶性脑缺血再灌注损伤发挥保护作用。
OBJECTIVE To investigate the protective effect of fenofibrate （Fen） on acute focal cerebral ischemia reperfusion in- jury in mice and its mechanisms. METHODS Cerebral ischemia was induced by middle cerebral artery occlusion in mice for 90min and then reperfusion. Fen （ 10, 80 mg kg-1 ） was intragastrically administered at the same time of reperfusion and 2 h after reperfu- sion respectively. The neurological deficit score,infarct volume and brain edema degree were determined 24 h after reperfusion. At the same time the expression of PPARα mRNA in brain tissue was measured by real-time RT-PCR. The contents of maiondialdehyde （MDA） and the activity of superoxide dismutase （SOD） in the brain tissue were measured by biochemical assay. The disruption of blood-brain barrier（ BBB）was evaluated by the extravasations of Evans Blue （EB）. MK886, an antagonist of PPARα receptor, was used to investigate the involvement of PPARa in the protective effect of Fen. RESULETS Fen （ 80 mg kg - 1 ） ameliorated neurolog- ical function, reduced infarct volume, attenuated brain edema degree, decreased the extravasations of EB, increased the expression of PPARα mRNA, and attenuated the lipid peroxidation in brain tissues. MK886 abolished the protective effect of Fen. CONCLUSION Fen has protective effect against acute focal cerebral ischemia reperfusion injury in mice by increasing the expression of PPARα mRNA and reducing lipid peroxidation in brain tissue.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2012年第13期1042-1047,共6页
Chinese Pharmaceutical Journal
基金
厦门市科技计划资助项目(3502Z20084022)
