注射用丹参多酚酸对MCAO/R大鼠Nrf2/Keap1/HO-1信号通路的影响  

Effect of Salvianolic Acid for Injection on Nrf2/Keap1/HO-1 signaling pathway in MCAO/R rats

作　　者：李汶泽 李智 倪秀一 万梅绪[2,3] 张燕欣 王蕴华 庄朋伟[1] 李德坤 鞠爱春[2,3] LI Wenze;LI Zhi;NI Xiuyi;WAN Meixu;ZHANG Yanxin;WANG Yunhua;ZHUANG Pengwei;LI Dekun;JU Aichun(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of Traditional Chinese Medicine Injections,Tianjin 300410,China;Heibei University of Chinese Medicine,Shijiazhuang 050200,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津天士力之骄药业有限公司,天津300410 [3]天津市中药注射剂安全性评价企业重点实验室,天津300410 [4]河北中医学院,河北石家庄050200

出　　处：《药物评价研究》2023年第8期1638-1644,共7页Drug Evaluation Research

摘　　要：目的 采用大鼠大脑中动脉栓塞/再灌注(MCAO/R)模型考察注射用丹参多酚酸(SAFI)对脑缺血再灌注大鼠核因子E2相关因子2(Nrf2)/Kelch样ECH相关蛋白(Keap1)/血红素氧合酶-1(HO-1)信号通路的影响。方法 线栓法构建大鼠MCAO/R模型,于术后24 h进行神经功能评分,将造模成功的大鼠随机分为模型组、丁苯酞(5 mL·kg^(-1))组和SAFI低、中、高剂量(5.76、11.51、23.02 mg·kg^(-1))组,尾iv给药,连续14 d。考察给药后各组大鼠神经功能缺损评分;ELISA法检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、脑源性神经营养因子(BDNF)水平;TTC染色法检测脑梗死体积;HE染色观察脑组织病理变化;Western blotting法检测Nrf2、Keap1、HO-1蛋白表达。结果 与模型组比较,SAFI中、高剂量组和丁苯酞组大鼠的神经功能缺损评分显著降低(P<0.05、0.01);SAFI各剂量组和丁苯酞组脑梗死体积显著减少(P<0.01、0.001),血清BDNF、SOD水平均显著升高(P<0.05、0.01、0.001),MDA水平显著降低(P<0.05、0.01),脑组织病理变化明显减轻,水肿减轻;SAFI高、中剂量组及丁苯酞组Keap1、Nrf2、HO-1蛋白表达显著升高(P<0.05、0.01、0.001),SAFI低剂量组Keap1、HO-1蛋白表达显著升高(P<0.01、0.001)。结论 SAFI可以减轻大鼠脑缺血再灌注损伤,可能是通过促进Nrf2/Keap1/HO-1信号通路,抑制氧化损伤实现的。Objective To investigate the effect of Salvianolic Acid for Injectionon(SAFI)on the Nrf2/Keap1/HO-1 signaling pathway in rats with cerebral ischemia-reperfusion using the rat middle cerebral artery occlusion/reperfusion(MCAO/R)model.Methods The rats were constructed with MCAO/R model using suture method,and rats with successful modeling were randomly divided into model groups,butylphthalide(5 mL·kg^(-1))group,SAFI low,medium,and high dose(5.76,11.51,and 23.02 mg·kg^(-1))group,with 17 rats in each group.According to the volume of 5 mL·kg^(-1),the rats in each group were injected into the tail vein for 14 d.After administration,the severity of neurological impairment in each group was scored.The contents of superoxide dismutase(SOD),malondialdehyde(MDA)and brain-derived neurotrophic factor(BDNF)in ischemic cerebral tissue were detected by ELISA.TTC staining was used to detect the cerebral infarct size.HE staining was used to observe the pathological changes of brain tissue.The expression of Nrf2/Keap1/HO-1 related pathway protein was detected by Western blotting.Results Compared with the model group,the neurological deficit scores of rats in the SAFI medium,high-dose,and butylphthalide groups were significantly reduced(P<0.05,0.01).The cerebral infarction volume was significantly reduced(P<0.01,0.001)in each dose group of SAFI and the butylphthalide group,while serum BDNF and SOD levels were significantly increased(P<0.05,0.01,0.001),MDA levels were significantly reduced(P<0.05,0.01),pathological changes in brain tissue were significantly reduced,and edema was alleviated.The expression of Keap1,Nrf2,and HO-1 proteins was significantly increased in the high and medium dose SAFI groups and the butylphthalide group(P<0.05,0.01,0.001),while the expression of Keap1 and HO-1 proteins was significantly increased in the low dose SAFI group(P<0.01,0.001).Conclusion SAFI can alleviate cerebral ischemia-reperfusion injury in rats.Its mechanism of action may be related to promote the Nrf2/Keap1/HO-1 signaling pathway and in

关 键 词：注射用丹参多酚酸 脑缺血/再灌注损伤 Nrf2/Keap1/HO-1信号通路 氧化损伤 

分 类 号：R285.5[医药卫生—中药学]