参红补血颗粒对气滞血瘀型血管内皮功能障碍小鼠血管内皮的保护作用及其机制  

Protective effect of Shenhong Buxue Granule on vascular endothelium of mice with vascular endothelial dysfunction of Qi stagnation and blood stasis type and its mechanism

作　　者：刘俊秀 周佳 律广富[2] 王雨辰 庄雪峰 赵嘉睿 黄晓巍[1] 李瑞丽 LIU Junxiu;ZHOU Jia;LYU Guangfu;WANG Yuchen;ZHUANG Xuefeng;ZHAO Jiarui;HUANG Xiaowei;LI Ruili(Department of Clinical Pharmacy and Pharmacology of Chinese Medicine,School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China;Department of Pharmacology of Traditional Chinese Medicine,Jilin Ginseng Academy,Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学药学院临床药学与中药药理教研室,吉林长春130117 [2]长春中医药大学吉林省人参研究科学院中药药理组,吉林长春130117

出　　处：《吉林大学学报（医学版）》2022年第6期1437-1447,共11页Journal of Jilin University：Medicine Edition

基　　金：吉林省卫健委科研项目(2021JC078);吉林省教育厅科研项目(JJKH20220872KJ);吉林省发改委创新能力建设项目(2021C011)。

摘　　要：目的:探讨参红补血颗粒(SBG)对气滞血瘀型血管内皮功能障碍(VED)模型小鼠血管内皮的保护作用和对人脐静脉内皮细胞(HUVECs)中Toll样受体4(TLR4)、髓样分化因子(MyD88)、核因子κBp65(NF-κB p65)及细胞间黏附分子1(ICAM-1)蛋白表达水平的影响,阐明其相关作用机制。方法:将60只昆明小鼠随机分为正常对照组、VED组、阳性对照组(0.62 g·kg^(-1)·d^(-1)血府逐瘀胶囊)、低剂量SBG(3 g·kg^(-1)·d^(-1))组、中剂量SBG(6 g·kg^(-1)·d^(-1))组和高剂量SBG(9 g·kg^(-1)·d^(-1))组,每组10只。除正常对照组外,其他各组小鼠采用冰水浴游泳法构建气滞血瘀型VED模型,连续给药造模21 d。观察各组小鼠行为表现,血液流变仪检测各组小鼠全血黏度,苏木精-伊红(HE)染色观察各组小鼠肺和胸主动脉组织病理形态表现,ELISA法检测各组小鼠血清血管性血友病因子(vWF)、血栓调节蛋白(TM)、ICAM-1、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平,试剂盒检测各组小鼠血清一氧化氮(NO)水平和胸主动脉组织中谷胱甘肽过氧化物酶(GSH-Px)及超氧化物歧化酶(SOD)活性。体外培养人脐静脉内皮细胞(HUVECs),分为正常对照组,叔丁基过氧化氢(TBHP)组,低、中和高剂量SBG组,除正常对照组外,其他4组HUVECs采用TBHP诱导HUVECs建立氧化损伤模型,采用MTT法检测各组HUVECs存活率,Western blotting法检测各组HUVECs中TLR4、MyD88、NF-κB p65和ICAM-1蛋白表达水平。结果:与正常对照组比较,VED组小鼠抓力值和自主活动次数明显降低(P<0.05),全血黏度明显升高(P<0.05);与VED组比较,阳性对照组和低、中及高剂量SBG组小鼠抓力值均明显升高(P<0.05),小鼠全血黏度明显降低(P<0.05),阳性对照组和高剂量SBG组小鼠自主活动次数明显升高(P<0.05)。HE染色,与正常对照组比较,VED组小鼠肺组织出现明显的毛细血管扩张和淤血,并且组织伴有大量炎性细胞浸润;与VED组比较,阳性对照�Objective:To investigate the protective effect of Shenhong Buxue Granules(SBG)on vascular endothelium of the mice with vascular endothelial dysfunction(VED)of Qi stagnation and blood stasis type and its effect on the expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor(MyD88),nuclear factorκB p65(NF-κB p65),intercellular adhesion molecule-1(ICAM-1)proteins in the human umbilical vein endothelial cells(HUVECs),and to elucidate its relevant action mechanism.Methods:A total of 60 Kunming mice were randomly divided into normal control group,VED group,positive control group(0.62 g·kg^(-1)·d^(-1) Xuefuzhuyu Capsule),low dose of SBG(3 g·kg^(-1)·d^(-1))group,medium dose of SBG(6 g·kg^(-1)·d^(-1))group and high dose of SBG(9 g·kg^(-1)·d^(-1))group,and there were 10 mice in each group.Except for normal control group,the mice in other groups were used to construct the VED models of Qi stagnation and blood stasis type with ice water bath method,and the mice were continuously administered for 21 d.The behavior of the mice in various groups were observed,the whole blood viscosities of the mice in various groups were measured by blood rheometer,HE staining was used to observe the pathomorphology of lung and thoracic aorta tissues of the mice in various groups,the serum levels of von Willebrand factor(vWF),thrombomodulin(TM),ICAM-1,and tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)of the mice in various groups were detected by ELISA method,and the kits were used to measure the levels of nitric oxide(NO)in serum and the activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in thoracic aorta tissue of the mice in various groups.The human umbilical vein endothelial cells(HUVECs)were cultured in vitro and divided into normal control group,tert-butyl hydroperoxide(TBHP)group and low,middle and high doses of SBG groups.Except for normal control group,the HUVECs in the other 4 groups were induced by TBHP to establish the oxidative damage model of HUVECs.The survival rates

关 键 词：参红补血颗粒 血管内皮功能障碍 氧化应激 TOLL样受体4 人脐静脉内皮细胞 

分 类 号：R96[医药卫生—药理学]