川芎嗪激活核因子相关因子-2 (Nrf-2)抑制高脂饮食喂养的Apo-E基因敲除小鼠的动脉粥样硬化  

The inhibitory effects of tetramethylpyrazine(TMP) on atherosclerosis in Apo-E knock-out and high-fat-diet fed mice by activating nuclear factor E_2-related factor-2 (Nrf-2)

作　　者：马慧[1] 任卫英[1] 袁颖[1] 沈继平[1] 胡予[1] 

机构地区：[1]复旦大学附属中山医院老年病科,上海200032

出　　处：《复旦学报（医学版）》2015年第1期90-95,共6页Fudan University Journal of Medical Sciences

摘　　要：目的观察川芎嗪能否通过激活核因子相关因子-2(nuclear factor E2-related factor 2,Nrf-2)从而减轻氧化应激所致的动脉粥样硬化损伤。方法 40只雄性载脂蛋白E(apolipoprotein-E,Apo-E)基因敲除小鼠随机分为4组,分别给予普通饮食+生理盐水腹腔注射(n=10)、高脂饮食+生理盐水腹腔注射(n=10)、高脂饮食+川芎嗪每天100mg/kg体重腹腔注射(n=10)、普通饮食+川芎嗪每天100mg/kg体重腹腔注射(n=10)。每天1次,持续8周,HE染色法观察主动脉粥样硬化改变,ELISA法检测血清和主动脉组织超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽S转移酶(glutathione S-transferase,GST)水平,Western blot法检测主动脉组织Nrf-2的蛋白表达,real-time PCR检测主动脉组织Nrf-2的mRNA表达。结果川芎嗪可显著降低高脂饮食喂养的Apo-E基因敲除小鼠主动脉斑块面积、内膜/中膜厚度比,增加血清和主动脉组织SOD和GST含量,增加主动脉组织中的总Nrf-2蛋白和核Nrf-2蛋白含量,增加Nrf-2mRNA相对表达量。结论川芎嗪通过促进Nrf-2mRNA的表达和核内转位,提高主动脉组织Nrf-2的因子浓度,进而促进下游各种抗氧化蛋白的表达,从而减轻氧化应激所致的动脉粥样硬化。Objective To observe whether tetramethylpyrazine （TMP） could alleviate the atherosclerosis in Apo-E knock-out mice through activating nuclear factor E2-related factor 2 （Nrf-2）. Methods Forty male Apo-E knock-out mice were randomly allocated to normal diet ＋ saline group （n = 10） ,high fat diet ＋ saline group （n= 10） ,high fat diet ＋ TMP group （n = 11）） ,or normal diet ＋ TMP group （71 = 11））. The mice of the TMP treatment group received daily intraperitoneal injection of TMP （101） mg/kg per day） and lasted for 8 weeks. Their aortic tissues were taken and tested as follow： the histological changes in the aortic were evaluated by hematoxylin-eosin （HE） stain. Superoxide dismutase （SOD） and glutathione S-transferase （GST） contents in aortic tissues and serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expressions of Nrf-2 protein were measured with Western blot and the expression of Nrf-2 mRNA with real-time PCR showed in aortic tissue of each group. Results TMP could reduce the plaque surface area in aorta and intima/media ratios in Apo-E knock-out mice fed with high fat diet,increase the SOD and GST contents, and increase the total and nuclear Nrf-2 protein in aortic tissue as well as Nrf-2 mRNA expression. Conclusions Tetramethylpyrazine could inhibit the atherosclerosis in Apo-E knock-out mice fed with high fat diet through the activation of transcription factor Nrf-2.

关 键 词：川芎嗪 动脉粥样硬化 核因子相关因子-2(Nrf-2) 

分 类 号：R972.6[医药卫生—药品]