补阳还五汤对脑缺血/再灌注损伤大鼠皮质区沉默信息调节因子1表达的影响  

Effect of Buyang Huanwu decoction on expression of silent information regulator 1 in cortical area of rats after cerebral ischemia/reperfusion injury

作　　者：辛紫媛 靳晓飞 周晓红[2] 赵艳萌 刘真一[2] 张彐宁 高维娟[1,2] XIN Zi-yuan;JIN Xiao-fei;ZHOU Xiao-hong;ZHAO Yan-meng;LIU Zhen-yi;ZHANG Xue-ning;GAO Wei-juan(Dept of Pathophysiology,Chengde Medical College,Chengde 067000,China;Hebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease,Hebei University of Chinese Medicine,Shijiazhuang 050091,China)

机构地区：[1]承德医学院病理生理学教研室,河北承德067000 [2]河北中医学院河北省心脑血管病中医药防治研究重点实验室,河北石家庄050091

出　　处：《中国药理学通报》2022年第12期1896-1901,共6页Chinese Pharmacological Bulletin

基　　金：中央引导地方科技发展资金项目(No 206Z7706G);河北中医学院科技能力提升一般项目(No KTY2019049);河北省中医药管理局科研计划项目(No 2021103)。

摘　　要：目的建立大鼠大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,探讨补阳还五汤对皮质区沉默信息调节因子1(silent information regulation 1,SIRT1)蛋白表达的影响,研究脑缺血/再灌注损伤(cerebral ischemia/reperfusion injury,CIRI)的可能作用机制。方法SD大鼠随机分为假手术组(Sham)、模型组(MCAO/R)、补阳还五汤组(BYHWT)、阿托伐他汀组(Atorvastatin),每组15只。缺血2 h/再灌注72 h及药物干预后,采用激光散斑血流监测视频系统评价模型建造成功。造模成功后通过Zea Longa神经功能学评分评价大鼠神经功能缺损情况;TTC染色检测脑梗死体积;尼氏染色观察神经细胞损伤情况;Western blot检测SIRT1蛋白表达水平;免疫荧光检测SIRT1荧光表达水平。结果与Sham组相比,MCAO/R组大鼠神经功能缺损严重(P<0.05);脑梗死体积增加(P<0.05);神经细胞损伤严重、排列紊乱、数量减少,细胞核固缩(P<0.05);SIRT1表达减少(P<0.05);SIRT1荧光强度减弱(P<0.05)。与MCAO/R组相比,BYHWT组和Atorvastatin组大鼠神经功能缺损减轻(P<0.05);脑梗死体积占比下降(P<0.05);神经细胞损伤减轻、数量增多(P<0.05);SIRT1表达增加(P<0.05);SIRT1荧光强度增强(P<0.05)。结论补阳还五汤可有效减轻脑缺血/再灌注大鼠的脑损伤,其发挥保护作用可能与提高缺血侧皮质区SIRT1蛋白表达有关。Aim To investigate the effect of Buyang Huanwu decoction on the expression of silencing regulation factor 1(SIRT1)protein in cortical area and the possible mechanism of cerebral ischemia/reperfusion injury(CIRI)via establishing middle cerebral artery occlusion(MCAO)model.Methods SD rats were randomly divided into sham group(Sham),model group(MCAO/R),Buyang huanwu decoction group(BYHWT),and atorvastatin group(Atorvastatin),with 15 rats in each group.After 2 h ischemia/reperfusion for 72 h and drug intervention,the model was successfully constructed by using laser speckle blood flow monitoring video system.Zea Longa neurological function score was used to evaluate the neurological defects of rats after modeling.TTC staining was used to detect infarct volume.Nissl staining was used to observe the injury of nerve cells.Western blot was employed to detect the SIRT1 protein expression level.Immunofluorescence was applied to detect the fluorescence expression of SIRT1.Results Compared with sham group,the neurological deficits of MCAO/R group were serious(P<0.05).Cerebral infarction volume increased(P<0.05).The nerve cells were severely damaged,disordered,with the nucleus pyknosis(P<0.05).SIRT1 protein expression was reduced(P<0.05).The fluorescence intensity of SIRT1 decreased(P<0.05).Compared with MCAO/R group,the neurological impairment degree of rats in BYHWT and Atorvastatin groups was reduced(P<0.05).The proportion of cerebral infarction volume decreased(P<0.05).The injury of nerve cells was significantly reduced and the number of nerve cells increased(P<0.05).The expression of SIRT1 protein was up-regulated(P<0.05).Fluorescence intensity of SIRT1 increased(P<0.05).Conclusions Buyang huanwu decoction can effectively alleviate brain injury in cerebral ischemia/reperfusion rats,and its protective effect may be related to the increase of SIRT1 protein expression in the ischemic cortical region.

关 键 词：补阳还五汤 脑卒中 脑缺血/再灌注损伤 组蛋白去乙酰化酶 SIRT1 SD大鼠 

分 类 号：R-332[医药卫生] R285.5R322.81R341R394R743.31