黄芩素-冰片抗脑缺血后内皮功能障碍的作用及机制  被引量:5

Effect and mechanism of baicalein-borneol on endothelial dysfunction after cerebral ischemia

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作  者:贺一凡 张行行 唐长杰 陈旭 崖壮举 周子烨 王斌[1] 韩朝军 刘继平[1] 史永恒[1] HE Yi-fan;ZHANG Hang-hang;TANG Chang-jie;CHEN Xu;YA Zhuang-ju;ZHOU Zi-ye;WANG Bin;HAN Chao-jun;LIU Ji-ping;SHI Yong-heng(School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Shangluo Traditional Chinese Medicine Hospital,Shangluo 726000,China)

机构地区:[1]陕西中医药大学药学院,陕西咸阳712046 [2]商洛市中医医院,陕西商洛726000

出  处:《中草药》2023年第22期7455-7465,共11页Chinese Traditional and Herbal Drugs

基  金:陕西省教育厅专项科研计划项目(21JK0608);陕西省中医药管理局中医药科研项目(2021-ZZ-JC023)。

摘  要:目的探究黄芩素、冰片及配伍对脑基底血管张力的影响和抗脑缺血后脑基底血管内皮功能障碍的作用及机制。方法采用离体血管环实验分别考察累积浓度的黄芩素、冰片及不同比例配伍对静息状态和内皮素-1(endothelin-1,ET-1)、血栓素A2类似物(U46619)、5-羟色胺(5-hydroxytryptamine,5-HT)预收缩的脑基底血管环张力的影响。利用线栓法构建局灶性脑缺血模型,给予不同比例的黄芩素-冰片,进行神经功能评分;采用红四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)染色观察脑梗死体积;荧光染色法观察缺血侧皮层CD34表达;检测缺血侧皮层一氧化氮(nitric oxide,NO)水平;苏木素-伊红(HE)染色观察脑基底动脉血管内皮完整性;Western blotting检测脑基底动脉内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达;ELISA法检测血清中炎性因子水平。结果黄芩素、冰片和各比例配伍组对基础状态血管环张力无明显影响,但能明显舒张由ET-1、U46619、5-HT预收缩的脑基底血管环(P<0.05、0.01),且随着浓度增大,黄芩素-冰片(1∶3)对ET-1、U46619预收血管环的舒张作用具有明显的优势。大脑中动脉局灶性梗死(middle cerebral artery occlusion,MCAO)术后大鼠神经功能评分显著升高(P<0.01),药物干预24 h后,神经功能评分不同程度降低(P<0.01);与假手术组比较,模型组大鼠脑梗死率显著升高(P<0.01),脑基底动脉内皮损伤严重、断裂,e NOS表达显著降低(P<0.05),iNOS表达显著升高(P<0.01),缺血侧皮层中CD34表达升高(P<0.01),NO水平显著降低(P<0.01),血清中白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平明显升高(P<0.01),转化生长因子-β(transforming growth factor-β,TGF-β)水平明显降低(P<0.01);而黄芩素-冰片能不同程度明显降低大鼠脑梗死率(P<0.01),改善脑基底�Objective To explore the effect and mechanism of baicalein,borneol and their combination on tension of cerebral basal vessels and their anti-endothelial dysfunction after cerebral ischemia.Methods In vitro vascular ring experiments was used to investigate the effects of cumulative concentrations of baicalein,borneol and different proportions of compatibility on tension of cerebral basal vascular ring pre-contracted by endothelin-1(ET-1),thromboxane A2 analog(U46619)and 5-hydroxytryptamine(5-HT)in resting state.A model of focal cerebral ischemia was constructed by thread occlusion method,different proportions of baicalein-borneol was given,neurological function score was performed;2,3,5-Triphenyl tetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarction;Fluorescence staining was used to observe the expression of CD34 in ischemic cortex;Level of nitric oxide(NO)in ischemic cortex was detected;Hematoxylin-eosin(HE)staining was used to observe the endothelial integrity of cerebral basal artery;Western blotting was used to detect the expressions of endothelial nitric oxide synthase(eNOS)and inducible nitric oxide synthase(iNOS)in basal artery of the brain;ELISA method was used to detect the levels of inflammatory factors in serum.Results The combination of baicalein,borneol and various proportions had no significant effect on basal vascular ring tension,but could significantly relax the brain basal vascular ring pre-contracted by ET-1,U46619 and 5-HT(P<0.05,0.01).As the concentration increased,baicalein-borneol(1∶3)had a significant advantage in the relaxation effect of ET-1,U46619 pre-contracted vascular rings.After middle cerebral artery occlusion(MCAO)surgery,the neurological function score of rats was significantly increased(P<0.01).After 24 h of drug intervention,the neurological function score was decreased to varying degrees(P<0.01);Compared with sham group,cerebral infarction rate of rats in model group was significantly increased(P<0.01),endothelial damage and rupture of cerebr

关 键 词:脑缺血 黄芩素 冰片 内皮功能障碍 血管环 

分 类 号:R285.5[医药卫生—中药学]

 

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