葛根通过雌激素受体调控内皮功能改善去卵巢大鼠冠脉微循环障碍的作用研究  

Modulation of Endothelial Function by Puerariae Lobatae Radix Through Estrogen Receptor to Improve Coronary Microcirculatory Disorders in Ovariectomized Rats

作　　者：崔宏伟 欧阳灿玥 陈兰英[1,2] 张莹 袁蓓欣 刘荣华[1] CUI Hongwei;OUYANG Canyue;CHEN Lanying;ZHANG Ying;YUAN Beixin;LIU Ronghua(Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;National Engineering Research Center for Solid Dosage Manufacturing Technology of Traditional Chinese Medicine,Nanchang 330006,China)

机构地区：[1]江西中医药大学,南昌330004 [2]中药固体制剂制造技术国家工程研究中心,南昌330006

出　　处：《中国药学杂志》2025年第4期373-383,共11页Chinese Pharmaceutical Journal

基　　金：江西中医药大学中药药效物质基础江西省重点实验室(2024SSY07102)。

摘　　要：目的研究葛根改善去卵巢大鼠冠脉微循环障碍(coronary microcirculation dysfunction,CMD)的作用。方法72只SD雌性大鼠,随机分为假手术组、模型组、戊酸雌二醇组、葛根水提物组(0.8、1.6、3.2 g·kg^(-1)),通过双侧去卵巢建立大鼠围绝经期模型,造模2周后,连续灌胃给药16周,每天1次,假手术组和模型组给予相应剂量的生理盐水。第16周末,PowerLab电生理记录仪检测大鼠血流动力学指标收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均压(mean blood pressure,MBP)、左室收缩压(left ventricular systolic pressure,LVSP)、左室舒张压(left ventricular diastolic pressure,LVDP)和等容收缩期左心室内压力最大上升和下降速率血脂四项甘油三酯;血液流变仪检测大鼠全血高、中、切黏度、血浆黏度和红细胞压积;全自动生化分析仪检测大鼠血浆中血脂四项(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及乳酸脱氢酶(lactic dehydrogenase,LDH)和肌酸激酶(creatine kinase,CK)的含量变化;HE染色观察大鼠心肌病理变化;DiI可视化技术观察冠脉微血管结构和形态的变化,AngioTool软件对血管面积、密度、直径、空隙度进行分析,根据泊肃叶公式计算微血管血流阻力;微孔法检测血清中一氧化氮(nitric oxide,NO)的含量变化;Elisa检测血清中内皮缩血管肽(endothelin-1,ET-1)、血管性血友病因子(von willebrand factor,vWF)的含量变化;Western blot检测心肌组织中雌激素受体α(estrogen receptorα,ERα)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR2)蛋白的表达。结果与模型组相比,葛根水提物可降低血流动力学中SBP、DBP、MBP、LVSP等血液流变学中全血高、中�OBJECTIVE To study the effect of Puerariae Lobatae Radix on improving coronary microcirculation disorders in ovariectomized rats.METHODS Seventy-two SD female rats were randomly divided into sham-operated group,model group,estradiol valerate group,and Puerariae Lobatae Radix aqueous extract groups(0.8,1.6,and 3.2 g·kg^(-1)),and the perimenopausal model of rat was established by bilateral de-ovulation.Two weeks after molding,drugs were continuously administered by gavage for 16 weeks,once a day,and the corresponding dose of saline was given to the sham-operated and model groups.At the end of the 16th week,PowerLab electrophysiological recorder was used to detect systolic blood pressure(SBP),diastolic blood pressure(DBP),mean blood pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVDP),and maximal left ventricular pressure rising rate(+dp/dt)and maximal left ventricular pressure decline rate(-dp/dt)in the rats.The whole blood high,middle and low shear viscosity,plasma viscosity and hematocrit of rats were detected by blood rheometer.The changes of four items of blood lipid low triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)lactate dehydrogenase(LDH),and creatine kinase(CK)in rat plasma;in plasma of rats were detected by automatic biochemical analyzer.HE staining was conducted to observe the pathological changes in rat myocardium.DiI visualization technology was used to observe the changes in the structure and morphology of coronary microvessels.AngioTool software was applied to analyze the vascular area,density,diameter,the degree of empty space,and according to Poisson Leaf′s formula the ion of microvascular resistance to blood flow was calculated.The content changes of nitric oxide(NO)in serum were detected by microtiter method.The content changes of endothelin-1(ET-1)and von Willebrand factor(vWF)in serum were detected by Elisa.Western blot was used to detect the expression of estrogen recep

关 键 词：葛根 去卵巢模型 雌激素 内皮功能 冠脉微循环 

分 类 号：R966[医药卫生—药理学]