替米沙坦对犬髂动脉再狭窄模型新生内膜增殖及血管重塑的影响  

Effects of telmisartan on neointimal proliferation and vascular remodeling in canine iliac artery restenosis model

作　　者：张大伟[1] 罗明尧[1] 方坤[1] 范博文 舒畅[1] ZHANG Da-wei;LUO Ming-yao;FANG Kun;FAN Bo-wen;SHU Chang(Department of Cardiovascular Surgery,Fuwai Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China)

机构地区：[1]中国医学科学院,北京协和医学院,阜外医院心血管外科,北京100037

出　　处：《中国临床药理学杂志》2022年第16期1940-1944,共5页The Chinese Journal of Clinical Pharmacology

基　　金：中央级公益性科研院所基本基金资助项目(2016ZX320002)。

摘　　要：目的探讨替米沙坦通过磷脂酰肌醇3-激酶/丝氨酸-苏氨酸激酶(PI3K/AKT)信号通路对犬髂动脉再狭窄模型新生内膜增殖及血管重塑的影响。方法30只雌性比格犬,随机分为假手术组、模型组和实验组,每组10只。采用手术结扎和缝扎方法建立犬髂动脉狭窄模型。模型组和实验组建立犬髂动脉狭窄模型,假手术组仅打开后腹腔,分离左髂卡总动脉。实验组在术后饲喂5 mg·kg^(-1)·d^(-1)替米沙坦,各组均干预4周。利用全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;采用噻唑蓝(MTT)法检测平滑肌细胞增殖率;取出左侧髂总动脉,采用计算机图像分析仪分析计算内膜/中膜比值(I/M);蛋白质印迹(Western Blot)法检测血管组织中PI3K/AKT信号通路相关蛋白表达水平。结果假手术组、模型组、实验组的TC水平分别为(2.43±0.21),(31.36±2.98)和(18.77±2.94)mmol·L^(-1);TG水平分别为(1.82±0.13),(7.05±0.74)和(3.82±0.81)mmol·L^(-1);HDL-C水平分别为(35.33±3.85),(3.26±0.16)和(21.22±2.49)mmol·L^(-1);LDL-C水平分别为(1.35±0.20),(23.64±3.27)和(14.27±2.06)mmol·L^(-1);新生内膜增殖率分别为(33.24±4.24)%,(80.26±7.14)%和(48.95±3.06)%;I/M分别为0,4.02±0.22和2.11±0.10;p-PI3K蛋白相对表达水平分别为0.30±0.03,0.88±0.08和0.42±0.04;p-AKT蛋白相对表达水平分别为0.30±0.03,0.87±0.08和0.38±0.03。上述指标,模型组与假手术组比较,或实验组与模型组比较,差异均有统计学意义(均P<0.05)。结论替米沙坦通过PI3K/AKT信号通路抑制犬髂动脉再狭窄模型新生内膜增殖。Objective To investigate the effect of telmisartan on neointimal proliferation and vascular remodeling in canine iliac artery restenosis model through phosphatidylinositol 3-kinase/serine-threonine kinase(PI3 K/AKT)signaling pathway.Methods Thirty female beagle dogs were randomly divided into sham operation group,model group and experimental group,with ten dogs in each group.A canine model of iliac artery stenosis was established by surgical ligation and suture.Model group and experimental group were established canine iliac artery stenosis model,sham operation group only open the abdominal cavity,separation of left iliac card common artery.The experimental group was fed with 5 mg·kg^(-1)·d^(-1)telmisartan after operation,and each group was intervened for 4weeks.Serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)levels were detected by automatic biochemical analyzer;the proliferation rate of smooth muscle cells was detected by MTT assay.The left common iliac artery was taken out,and the ratio of intima to membrane(I/M)was analyzed and calculated by computer image analyzer.The expression of PI3K/AKT signaling pathway related proteins in vascular tissues was detected by Western Blot.Results TC levels in sham operation group,model group and experimental group were(2.43±0.21),(31.36±2.98)and(18.77±2.94)mmol·L^(-1),respectively;TG levels were(1.82±0.13),(7.05±0.74)and(3.82±0.81)mmol·L^(-1),respectively;HDL-C levels were(35.33±3.85),(3.26±0.16)and(21.22±2.49)mmol·L^(-1),respectively;LDL-C levels were(1.35±0.20),(23.64±3.27)and(14.27±2.06)mmol·L^(-1),respectively;neointimal proliferation rates were(33.24±4.24)%,(80.26±7.14)%and(48.95±3.06)%,respectively;the I/M of the three groups were 0,4.02±0.22 and 2.11±0.10,respectively.The relative expression levels of p-PI3K protein in these three groups were 0.30±0.03,0.88±0.08 and 0.42±0.04,respectively.The relative expression levels of p-AKT protein were0.30±0.03,0.87±0.0

关 键 词：替米沙坦 磷脂酰肌醇3-激酶/丝氨酸-苏氨酸激酶信号通路 犬 髂动脉再狭窄 

分 类 号：R97[医药卫生—药品]