芩栀猪胆方对血管性痴呆大鼠血管新生的作用及机制研究  

Effect and mechanism of Qinzhi Zhudan prescription on angiogenesis in vascular dementia rats

作　　者：孙春燕 高颖[1,2,3] 程发峰 王雪茜 徐甜 刘凤智 徐文秀 张泽涵 王庆国 SUN Chunyan;GAO Ying;CHENG Fafeng;WANG Xueqian;XU Tian;LIU Fengzhi;XU Wenxiu;ZHANG Zehan;WANG Qingguo(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院脑病二科,100700 [2]北京中医药大学中医脑病研究院 [3]国家中医药管理局脑病中医证治重点研究室 [4]北京中医药大学中医学院

出　　处：《环球中医药》2022年第12期2329-2335,共7页Global Traditional Chinese Medicine

基　　金：国家自然科学基金联合基金重点项目(U21A20400);国家自然科学基金(81973789);国家科技重大专项(民口)课题(2019ZX09301-173)。

摘　　要：目的观察芩栀猪胆方对血管性痴呆大鼠血管新生的作用及其机制。方法将Wistar大鼠随机分为4组:空白对照组、模型组、芩栀猪胆组和尼莫地平组。采用改良双侧颈总动脉永久结扎术复制血管性痴呆模型。造模后第2天,芩栀猪胆组和尼莫地平组分别给予芩栀猪胆和尼莫地平灌胃治疗,模型组及空白对照组给予等体积的去离子水灌胃,每日1次,连续28天。运用Morris水迷宫测试大鼠学习记忆能力;苏木素—伊红染色(Hemotaxylin-eosin staining,HE)观察海马组织病理形态学改变;免疫组化法检测海马脑微血管密度及血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)表达;实时荧光定量PCR检测大鼠海马组织VEGF mRNA、VEGFR2 mRNA水平。结果(1)与空白对照组比较,模型组大鼠逃避潜伏期增加,穿越平台次数减少(P<0.05)。与模型组比较,芩栀猪胆组与尼莫地平组逃避潜伏期均缩短,穿越平台次数增加(P<0.05)。芩栀猪胆组、尼莫地平组之间逃避潜伏期、穿越平台次数比较无明显差异(P>0.05)。(2)与空白对照组比较,模型组大鼠微血管密度、VEGFA、VEGFR2水平均增加(P<0.05),VEGFA mRNA、VEGFR2 mRNA水平有上升趋势。与模型组比较,芩栀猪胆组与尼莫地平组微血管密度、VEGFA、VEGFR2蛋白及mRNA水平均增加(P<0.05);芩栀猪胆组与尼莫地平组之间微血管密度、VEGFA、VEGFR2蛋白及mRNA水平无明显差异(P>0.05)。结论芩栀猪胆方可以提高血管性痴呆大鼠学习记忆能力,上调海马组织VEGFA、VEGFR2蛋白及mRNA水平,促进海马组织血管新生。Objective To observe the effect and mechanism of Qinzhi Zhudan prescription on angiogenesis in vascular dementia rats.Methods Wistar rats were randomly divided into 4 groups:the blank control group,the model group,the Qinzhi Zhudan group and the nimodipine group.The Qinzhi Zhudan group and the nimodipine group were given intragastric administration of Qinzhi Zhudan and nimodipine on the 2nd day after modeling,while the model group and the blank control group were given intragastric administration of deionized water,once a day,for consecutive 28 days.Morris water maze was used to test the learning and memory ability of rats,and HE staining was used to observe the histopathological changes of hippocampal tissues.Immunohistochemistry was used to detect the microvascular density and expression of VEGF and VEGFR2 in hippocampus.Quantative real-time PCR was used to detect the mRNA levels of VEGF and VEGFR2 in rat hippocampus.Results(1)Compared with the blank control group,the escape latency of rats in the model group was increased,and the number of crossing platform was decreased(P<0.05).Compared with the model group,the escape latency of Qinzhi Zhudan group and the nimodipine group was decreased,and the number of crossing platform was increased(P<0.05).There were no significant differences in escape latency and crossing times between the Qinzhi Zhindan group and the nimodipine group(P>0.05).(2)Compared with the blank control group,microvessel density,VEGFA,and VEGFR2 levels were increased in the model group(P<0.05),VEGFA mRNA and VEGFR2 mRNA levels in the model group showed an upward trend.Compared with the model group,the density of escape microvessel,the protein and mRNA levels of VEGFA and VEGFR2 were increased in the Qinzhi Zhudan group and the nimodipine group(P<0.05).There were no significant differences in microvessel density,VEGFA,VEGFR2 protein and mRNA levels between the Qinzhi Zhudan group and the nimodipine group(P>0.05).Conclusion Qinzhi Zhudan prescription can improve the learning and memory ability of v

关 键 词：血管性痴呆 芩栀猪胆方 血管新生 血管内皮生长因子 血管内皮生长因子受体 

分 类 号：R285.5[医药卫生—中药学]