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替米沙坦对兔髂动脉再狭窄模型中连接蛋白43表达及新生内膜增生的影响

The effect of Telmisartan on the expression of connexin43 and neointimal hyperplasia in a rabbit iliac artery restenosis model.

作者信息

Cao Lu, Zhao Cui, Cong Hongliang, Hou Kai, Wan Lianghui, Wang Jixiang, Zhao Lili, Yan Haiyang

机构信息

Cardiology Department, Tianjin Chest Hospital, Tianjin, 300222, People's Republic of China.

National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.

出版信息

Heart Vessels. 2019 Jul;34(7):1230-1239. doi: 10.1007/s00380-018-01338-1. Epub 2019 Jan 22.

Abstract

We established a rabbit iliac artery restenosis model to explore the impact of Telmisartan on the expression of Connexin43 (Cx43) and neointimal hyperplasia. Thirty New Zealand white rabbits were randomly divided into three groups: control group (n = 10), restenosis group (n = 10), and Telmisartan group (n = 10). The restenosis model was established by high-cholesterol diet combined with double-balloon injury of iliac arteries. In addition, Telmisartan at 5 mg/(kg day) was administered to the rabbits of Telmisartan group on the second day after the second balloon injury. All rabbits were killed at the end of the experiment followed by institution policy. Before sacrifice, blood samples were obtained to test serum angiotensinII (AngII). Iliac arteries were isolated for morphological analysis and determining the expression of Cx43 by HE staining, immunohistochemical analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western Blotting analysis. Then, the local AngII levels of arteries were measured by radioimmunoassay. As compared with controls, the expression of Cx43 mRNA (0.98 ± 0.08) vs. (1.27 ± 0.17), P < 0.01), and Cx43 protein [(0.75 ± 0.08) vs. (0.90 ± 0.08), P < 0.05] of restenosis group were increased, which were significantly higher than those of Telmisartan group [Cx43 mRNA: (1.27 ± 0.17) vs. (1.00 ± 0.20), P < 0.01; Cx43 protein: (0.90 ± 0.08) vs. (0.82 ± 0.05), P < 0.05]. Furthermore, The intima thickness [(266.12 ± 70.27) vs. (2.85 ± 0.19) μm, P < 0.01] and the local AngII [(115.6 ± 15.7) vs. (90.1 ± 7.7), P < 0.05] of restenosis group were raised when compared with controls. Telmisartan group exhibited thinner intima compared with restenosis group [(68.22 ± 24.37) vs. (266.12 ± 70.27), P < 0.01]. However, the local AngII levels between these two groups were approximate. In addition, the plasma concentration of AngII was not significantly different among three groups. In conclusion, Telmisartan can inhibit the expression of connexin43 and neointimal hyperplasia in iliac artery restenosis model.

摘要

我们建立了兔髂动脉再狭窄模型,以探讨替米沙坦对连接蛋白43(Cx43)表达及内膜增生的影响。30只新西兰白兔随机分为三组:对照组(n = 10)、再狭窄组(n = 10)和替米沙坦组(n = 10)。通过高胆固醇饮食联合髂动脉双球囊损伤建立再狭窄模型。此外,在第二次球囊损伤后第二天,给替米沙坦组的兔子给予5mg/(kg·天)的替米沙坦。实验结束时,按照机构规定处死所有兔子。处死前,采集血样检测血清血管紧张素II(AngII)。分离髂动脉进行形态学分析,并通过苏木精-伊红(HE)染色、免疫组织化学分析、逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析来测定Cx43的表达。然后,通过放射免疫测定法测量动脉局部AngII水平。与对照组相比,再狭窄组Cx43 mRNA(0.98±0.08 vs. 1.27±0.17,P<0.01)和Cx43蛋白[(0.75±0.08)vs.(0.90±0.08),P<0.05]表达增加,且显著高于替米沙坦组[Cx43 mRNA:(1.27±0.17)vs.(1.00±0.20),P<0.01;Cx43蛋白:(0.90±0.08)vs.(0.82±0.05),P<0.05]。此外,与对照组相比,再狭窄组内膜厚度[(266.12±70.27)vs.(2.85±0.19)μm,P<0.01]和局部AngII[(115.6±15.7)vs.(90.1±7.7),P<0.05]升高。与再狭窄组相比,替米沙坦组内膜更薄[(68.22±24.37)vs.(266.12±70.27),P<0.01]。然而,两组之间局部AngII水平相近。此外,三组之间血浆AngII浓度无显著差异。总之,在兔髂动脉再狭窄模型中,替米沙坦可抑制连接蛋白43的表达及内膜增生。

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