替米沙坦对兔髂动脉再狭窄模型新生内膜增殖的影响  

Impact of telmisartan on neointimal hyperplasia in a rabbit iliac artery restenosis model

作　　者：曹路[1] 赵翠[2] 丛洪良[1] 毛用敏[3] 赵莉莉[3] 王霁翔[1] 王菁[4] 赵福梅[3] 

机构地区：[1]天津市胸科医院心内科,天津300051 [2]中国人民武装警察部队后勤学院附属医院心内科 [3]天津市心血管病研究所 [4]天津市胸科医院病理科

出　　处：《中华高血压杂志》2015年第5期445-451,共7页Chinese Journal of Hypertension

基　　金：天津市卫生局攻关项目(11KG123)

摘　　要：目的观察兔髂动脉再狭窄模型病理改变,并加用替米沙坦进行干预,探讨其对再狭窄模型新生内膜增殖的影响。方法 30只新西兰大白兔随机分为对照、再狭窄和替米沙坦组,每组10只。采用高脂饲料喂养联合兔髂动脉二次球囊损伤建立再狭窄模型,其中替米沙坦组于第二次球囊损伤后第2天开始加用替米沙坦5mg/(kg·d)。实验结束时,动物处死前采血检测总胆固醇,并留取髂动脉标本,行苏木精伊红染色法染色及免疫组化检测,组织匀浆测定血管紧张素Ⅱ(AngⅡ)水平。结果与对照组比较,再狭窄和替米沙坦组总胆固醇[(20.44±0.68)、(20.39±0.60)比(0.58±0.19)mmol/L]、血管壁AngⅡ[(115.6±15.7)、(123.8±22.1)比(90.1±7.7)ng/L]、内膜厚度[(266.1±70.3)、(68.2±24.4)比(2.8±0.2)μm]和狭窄率[(89.3±6.9)%、(42.6±18.1)%比(23.0±3.5)%]增加(均P<0.05)。而替米沙坦组的内膜厚度和狭窄率低于再狭窄组(均P<0.01)。与对照和替米沙坦组比较,再狭窄组平滑肌细胞增殖率明显增加[(21.9±4.7)%比(7.3±4.9)%、(7.1±5.1)%,均P<0.01]。α平滑肌肌动蛋白染色证实,再狭窄和替米沙坦组的新生内膜主要细胞成分为血管平滑肌细胞。结论替米沙坦对兔髂动脉再狭窄模型血管平滑肌细胞增殖及新生内膜增殖均有抑制作用。Objective To explore the impact of telmisartan on neointimal hyperplasia via observing the pathological changes in a rabbit iliac artery restenosis model. Methods Thirty New Zealand white rabbits were randomly and e- venly divided into 3 groups： control group （n=10）, restenosis group {n=10）, and telmisartan group {n=10}. The restenosis model was established by high-fat diets coupled with double-balloon injury of iliac arteries. Addi- tionally, telmisartan at 5 mg/（kg · d} was administrated to the rabbits in telmisartan group on the second day after the second balloon injury. All rabbits were killed at the end of this experiment. Before sacrifice, blood samples were obtained to measure total cholesterol （TC） and angiotensin Ⅱ fAng Ⅱ ）. Iliac arteries were cut down for HE staining, immunohistochemical analysis, and measurement of local Ang Ⅱ levels. Results Rabbits in restenosis group and telmisartan group had significant higher levels of TC [（20.44±0.68] and （20.39±0.60] vs （0.58± 0.19） mmol/L], Ang Ⅱ [（115.6±15.7） and （123.8±22.1） vs （90.1±7.7）ng/L], intima thickness [（266.1± 70.3） and （68.2±24.4） vs （2.8＋0.2）/xm], and stenosis rates [（89.3±6.9）% and （42.6±18.1}M vs （23.0± 3.5） %] than rabbits in control group （all P〈0.05）. Furthermore, telmisartan group revealed lower stenosis rates and thinner intima compared with restenosis group （all P〈0.01 ）. Cell growth rate in restenosis group （21.9 ± 4.7 ） % ] was significantly increased relative to control group [ （ 7.3 ± 4.9 ） % ] and telmisartan group [ （ 7.1 ± 5.1 ） % ] （both P〈0.01）. In neointima, vascular smooth muscle cells （VSMC） were identified as the proliferated cells in both restenosis group and telmisartan group through a-smooth muscle actin staining. Conclusion Telmisartan can inhibit the proliferation of VSMC and neointimal hyperplasia in a rabbit iliac artery restenosis model.

关 键 词：再狭窄 血管平滑肌细胞 新生内膜增殖 血管紧张素Ⅱ 替米沙坦 

分 类 号：R965[医药卫生—药理学]