山茱萸环烯醚萜苷对脑缺血再灌注大鼠线粒体损伤的影响  

Effects of cornel iridoid glycoside on mitochondria damage in rats with cerebral ischemia reperfusion injury

作　　者：王明洋 孙争宇[1] 张丽[1] 李雅莉[1] 李林[1] 张兰[1] Wang Mingyang;Sun Zhengyu;Zhang Li;Li Yali;Li Lin;Zhang Lan(Department of Pharmacy,Xuanwu Hospital,Captial Medical University,Beijing Engineering Research Center for Nerve System Drugs,Beijing Institute for Brain Disorders,Key Laboratory for Neurodegenerative Disease of Ministry of Education,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院药学部、北京市神经药物工程技术研究中心、北京脑重大疾病研究院、神经变性病教育部重点实验室,北京100053

出　　处：《首都医科大学学报》2020年第3期385-390,共6页Journal of Capital Medical University

基　　金：国家自然科学基金(81673406,81874351);国家重大新药创制专项(2015ZX09101-016);北京市博士后科研基金(2018-ZZ-112);北京市医院管理中心登峰人才计划(DFL20190803)。

摘　　要：目的研究山茱萸环烯醚萜苷(cornel iridoid glycoside,CIG)对大脑中动脉梗阻(middle cerebral artery occlusion, MCAO)模型大鼠大脑皮质线粒体损伤的作用,探讨CIG对脑缺血再灌注损伤的保护作用机制。方法采用线栓法制备大鼠MCAO模型,缺血2 h后复灌,采用数字表法将大鼠随机分为5组:假手术组,模型组,CIG低、高剂量(60、120 mg/kg)给药组,阳性对照药银杏叶片组,于复灌6 h后开始灌胃给药,每日1次,连续给药7 d。采用神经功能缺损症状评分(Modified Neurological Severity Scores,mNSS)评价各组大鼠神经功能情况,透射电镜观察损伤侧皮质部位线粒体超微结构,Western blotting法检测线粒体功能相关的蛋白NIX、Beclin1、DRP1、OPA1和PGC-1α的表达。结果脑缺血再灌注损伤7 d后,模型组大鼠mNSS评分较假手术组大鼠显著增高,而与模型组相比,各给药组大鼠的mNSS评分明显降低。透射电镜结果显示模型组大鼠皮质线粒体损伤严重,CIG给药能明显改善线粒体结构变化。Western blotting检测结果显示,缺血再灌注损伤可显著抑制大鼠皮质组织中NIX、Beclin1、DRP1、OPA1和PGC-1α蛋白的表达,而CIG给药后均能显著改善这些蛋白的异常表达。结论 CIG通过激活线粒体自噬,促进线粒体分裂融合,增加线粒体生物合成等过程,减轻线粒体损伤,进而保护神经元,发挥较好的抗脑缺血再灌注损伤的脑保护作用。Objective To investigate the effects of cornel iridoid glycoside(CIG)on the mitochondria damage induced by cerebral ischemia reperfusion injury in middle cerebral artery occlusion(MCAO)rats.Methods Male SD rats were subjected to MCAO surgery and the right artery was occluded for 2 h followed by reperfusion.All rats were randomly divided into 5 groups(n=6):sham group,model group,CIG 60mg/kg group,CIG 120 mg/kg group,and extract of Ginkgo biloba(EGB)group.Drugs were intragastrically administered at 6th hour after reperfusion,once a day for 7 days.Modified Neurological Severity Scores(mNSS)was carried out to evaluate the neurological functioning in MCAO rats.The mitochondrial ultrastructure in injured cortex of MCAO rats was detected by transmission electron microscopy.The expression of mitochondrial function related proteins NIX,Beclin1,DRP1,OPA1,and PGC-1αwere evaluated using Western blotting.Results The MCAO rats scored significantly higher in mNSS,and mitochondrial ultrastructure was damaged in injured cortex.Furthermore,the expression of NIX,Beclin1,DRP1,OPA1,and PGC-1αwere also remarkably downregulated in the injured cortex of MCAO rats.While treatment with CIG declined the mNSS scores,ameliorated the mitochondrial injury,and significantly increased the expression of NIX,Beclin1,DRP1,OPA1,and PGC-1αin the injured cortex of MCAO rats.Conclusion CIG treatment could increase the mitochondrial biogenesis,fission and fusion process,and activate the mitophagy,hence ameliorate the mitochondrial injury,promote the recovery of neurological function after MCAO injury in rats.Our research showed that CIG may be a candidate drug for cerebral stroke therapy.

关 键 词：山茱萸环烯醚萜苷 脑缺血再灌注 神经保护 线粒体损伤 线粒体自噬 线粒体分裂融合 

分 类 号：R743[医药卫生—神经病学与精神病学]