辣椒素对AngⅡ诱导VSMC增殖迁移及DOCA-盐引起的高血压大鼠血管重构的影响  

Effects of Capsaicin on Proliferation and Migration of VSMC Induced by AngⅡand Vascular Remodeling in Rats with DOCA-Salt-Induced Hypertension

作　　者：周毅 王雪笠 黎炳护 朱艳霞 甄宁 高利涛 刘军 王丽 智建霞 张莉莉 ZHOU Yi;WANG Xue-li;LI Bing-hu;ZHU Yan-xia;ZHEN Ning;GAO Li-tao;LIU Jun;WANG Li;ZHI Jian-xia;ZHANG Li-li(Department of Neurology,the 980th Hospital of PLA Joint Logistics Support Forces,Shijiazhuang 050082,China;Department of Neurology,Army Characteristic Medical Center,PLA Army Medical University,Chongqing 400042,China)

机构地区：[1]解放军联勤保障部队第九八〇医院神经内科,石家庄050082 [2]解放军陆军军医大学特色医学中心神经内科,重庆400042

出　　处：《解放军医药杂志》2022年第1期7-13,共7页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：河北省卫健委重点研究计划(20191190);河北省卫健委重点研究计划(20210311);重庆市技术创新与应用发展专项面上项目(cstc2019jscx-msxmX0285)。

摘　　要：目的探讨辣椒素(Cap)对血管紧张素Ⅱ(AngⅡ)诱导血管平滑肌细胞(VSMC)增殖迁移及醋酸去氧皮质酮(DOCA)-盐引起的高血压大鼠血管重构的影响。方法40只WKY大鼠根据不同干预措施分为对照组(Con组),肩胛部皮下注射普通植物油,普通饲料喂养,正常饮水;模型组(DOCA组)予DOCA-盐干预;DOCA+Cap组,在DOCA组基础上饲料中添加0.01%Cap;DOCA+Cap+CapZ组,在DOCA+Cap组基础上饲料中添加0.01%辣椒素抑制剂(CapZ)。采用大鼠胸主动脉组织原代培养VSMC;通过AngⅡ诱导VSMC,分为空白对照组(不予任何干预)、AngⅡ组(AngⅡ100 nmol/L)、AngⅡ+Cap组(AngⅡ100 nmol/L+Cap 1μmol/L)、AngⅡ+Cap+CapZ组(AngⅡ100 nmol/L+Cap 1μmol/L+CapZ 1μmol/L),并应用MTT和Western blot法检测增殖细胞核抗原(PCNA)表达的方法观察细胞增殖情况,应用划痕实验及检测基质金属蛋白酶-9(MMP-9)表达的方法观察细胞迁移情况;应用鼠尾血压测定仪检测Cap对DOCA-盐引起大鼠血压升高的抑制作用;HE染色观察各组大鼠颈动脉内膜增生变化。结果细胞迁移及增殖情况,AngⅡ组大于空白对照组,AngⅡ+Cap组小于AngⅡ组,AngⅡ+Cap+CapZ组大于AngⅡ+Cap组(P<0.05);PCNA和MMP-9表达水平,AngⅡ组大于空白对照组,AngⅡ+Cap组小于AngⅡ组,AngⅡ+Cap+CapZ组大于AngⅡ+Cap组(P<0.05)。DOCA组收缩压(SBP)较Con组显著升高(P<0.05);DOCA+Cap组SBP较DOCA组升高程度明显减小(P<0.05);DOCA+Cap+CapZ组SBP较DOCA+Cap组又明显升高(P<0.05)。颈动脉内膜增生程度,DOCA组明显大于Con组,DOCA+Cap组明显小于DOCA组,DOCA+Cap+CapZ组明显大于DOCA+Cap组(P<0.05)。结论Cap能够抑制AngⅡ诱导VSMC的增殖迁移,降低DOCA-盐引起的大鼠血压升高及减轻因高血压引起的颈动脉内膜增生。Objective To investigate effects of Capsaicin(Cap)on proliferation and migration of vascular smooth muscle cell(VSMC)induced by AngⅡand vascular remodeling in rats with Deoxycorticosterone Acetate(DOCA)-salt-induced hypertension.Methods Forty WKY rats were divided into control group(Con group),model group(DOCA group),DOCA+Cap group and DOCA+Cap+CapZ group according to different intervention measures.Con group was injected with normal vegetable oil subcutaneously into the scapula with normal feeding and drinking water.DOCA group received DOCA-salt intervention.DOCA+Cap group was added with 0.01%Cap to the diet on the basis of treatment for DOCA group.DOCA+Cap+CapZ group was added with 0.01%Capsaicin inhibitor(CapZ)to the diet on the basis of treatment for DOCA+Cap group.VSMCs were primary cultured by using thoracic aorta in rats.VSMCs were induced by AngⅡ,and then they were divided into blank control group(no intervention),AngⅡgroup(AngⅡ100 nmol/L),AngⅡ+Cap group(AngⅡ100 nmol/L+Cap 1μmol/L)and AngⅡ+Cap+CapZ group(AngⅡ100 nmol/L+Cap 1μmol/L+CapZ 1μmol/L).The condition of cell proliferation was observed by using MTT assay and Western Blot methods to detect expression of proliferating cell nuclear antigen(PCNA).The condition of cell migration was observed by using scratch test and detecting expression of matrix metalloproteinase-9(MMP-9)in the cells.The inhibitory effect of Cap on the increased hypertension induced by DOCA-salt in rats was detected by rat tail blood pressure analyzer.HE staining was used to observe changes of carotid intimal hyperplasia in rats.Results Conditions of cell migration and proliferation in AngⅡgroup were significantly higher than those in blank control group,and the conditions in AngⅡ+Cap group were significantly lower than those in AngⅡgroup,while the conditions in AngⅡ+Cap+CapZ group were significantly higher than those in AngⅡ+Cap group(P<0.05).Expressions of PCNA and MMP-9 in AngⅡgroup were significantly higher than those in blank control group,and the e

关 键 词：辣椒素 高血压 大鼠 血管平滑肌细胞 细胞增殖 细胞运动 血管重构 

分 类 号：R544.1[医药卫生—心血管疾病] R-332[医药卫生—内科学]