中国药理学通报2016，Vol.32Issue(6)：846-852,853,8.DOI:10.3969/j.issn.1001-1978.2016.06.021
高血糖通过抑制线粒体自噬加重大鼠脑缺血／再灌注损伤
Hyperglycemia aggravated cerebral ischemia/reperfusion injury by inhibiting mitophagy
左玮 1梅丹1
作者信息
- 1. 中国医学科学院北京协和医学院北京协和医院，北京 100730
- 折叠
摘要
Abstract
Aim Toinvestigatetheroleofhyperglyce-mia in cerebral ischemia/reperfusion(I/R)injury with a middle cerebral artery occlusion(MCAO)rat model anditsmechanism.Methods EightyhealthymaleSD rats were randomly assigned into sham group, I/R group (normoglycemia),hyperglycemic I/R groupⅠ(HG1 )and hyperglycemic I/R groupⅡ(HG2 ).The cerebral I/R model was established by occluding the middle cerebral artery(MCA)in rats.Hyperglycemia was induced by intraperitoneal injection of 50% glu-cose solution.Neurological deficit was determined by Ludmila Belayev test;infarct size and brain edema were measured by TTC staining;mitophagy was ob-served by double immunofluorescent staining and elec-tron microscope.The expressions of autophagy-related proteins(LC3 and Beclin-1 )and apoptosis-related pro-teins(Cyt-C,AIF,caspase-9 and caspase-3 )were ex-aminedbyWesternblotfurtherly.Results Bloodglu-cose level was controlled at 4 mmol·L-1 (normoglyce-mia),10 mmol · L-1 (HG1 ) and 20 mmol · L-1 (HG2)respectively.There were no significant differ-ences between model group and HG1 group in neuro-logical deficit scores,infarct volume and edema size(P>0. 05 ).However,these indications in HG2 group were significantly increased compared with model group (P<0. 05 ).After 3 days of reperfusion,the level of mitophagy was significantly reduced accompanied with increased mitochondria damages in HG 2 group (P <0. 05 ),and the expressions of mitochondrial related ap-optotic proteins(Cyt-C,AIF,caspase-9 and caspase-3 ) were significantly increased accordingly compared to modelgroup.Conclusions Mildhyperglycemiacan not intensify the cerebal ischemic injury.In contrast, severe hyperglycemia significantly aggravates the brain ischemic injury by inhibiting the removal of injured mi-tochondria in a manner of mitophagy,thus amplifying the mitochondrial mediated cascade damage responses.关键词
脑梗死/高血糖/线粒体自噬/TTC染色/凋亡/神经功能/线粒体Key words
brain ischemia/hyperglycemia/mitoph-agy/TTC staining/apoptosis/neurological function/mi-tochondrian分类
医药卫生引用本文复制引用
左玮,梅丹..高血糖通过抑制线粒体自噬加重大鼠脑缺血／再灌注损伤[J].中国药理学通报,2016,32(6):846-852,853,8.
