高盐饮食诱导Wistar大鼠颈动脉重塑的机制及替米沙坦的干预
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国家自然科学基金资助(81160041);贵州省社会发展攻关计划项目和省高层次人才科研条件特助项目[黔科合SY字(2011)3047号,TZJF-2009年-42]


Effects of High Salt Diet on the Remodeling of Carotid Arteries and the Intervention of Telmisartan in Wistar Rats
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    目的 探讨高盐饮食对Wistar大鼠颈动脉重塑的影响及替米沙坦的干预作用。方法 Wistar大鼠60只随机分为对照组(0.5%NaCl颗粒饲料)、高盐组(8%NaCl颗粒饲料)和干预组(8%NaCl颗粒饲料+替米沙坦)。实验结束后,根据尾动脉血压将高盐组分为高盐高血压组和高盐血压正常组。采用HE染色、Masson染色及免疫组织化学染色检测颈动脉中膜形态结构变化及颈动脉中膜α-平滑肌肌动蛋白(α-actin)、增殖细胞核抗原(PCNA)、血管紧张素Ⅱ(AngⅡ)、血管紧张素Ⅱ 1型受体(AT1)、血管紧张素Ⅱ 2型受体(AT2)、转化生长因子β1(TGF-β1)、p-Smad2/3、Smad7的表达水平。放射免疫法测定颈动脉醛固酮(ALD)含量。结果 高盐高血压组和高盐血压正常组颈动脉中膜厚度(MT)、颈动脉中膜厚度与腔径比(MT/LD)、颈动脉中膜平滑肌细胞增殖指数(PI)、胶原纤维面积百分比、TGF-β1和p-Smad2/3表达均增高(P<0.05),干预组上述指标均降低(P<0.05),Smad7在高盐高血压组、高盐血压正常组颈动脉表达减少,在干预组颈动脉表达增加(P<0.05)。高盐高血压组、高盐血压正常组和干预组颈动脉中膜AngⅡ表达均较对照组增多(P<0.05),此三组之间无明显差异(P>0.05)。高盐高血压组和高盐血压正常组颈动脉中膜AT1表达较对照组增多,干预组颈动脉中膜AT1表达减少(P<0.05),高盐高血压组与高盐血压正常组相比无明显差异(P>0.05)。干预组颈动脉中膜AT2表达较对照组、高盐高血压组、高盐血压正常组增多(P<0.05),对照组、高盐高血压组和高盐血压正常组之间无明显差异(P>0.05)。高盐高血压组颈动脉中膜醛固酮含量高于对照组、高盐血压正常组和干预组(P<0.05或P<0.01)。结论 8%NaCl盐饮食可诱导Wistar大鼠颈动脉重塑,其机制可能与局部RAS和TGF-β1/Smads通路中多个组分的表达异常有关,替米沙坦能抑制高盐诱导的颈动脉重构。

    Abstract:

    Aim To investigate the effect of high salt diet on carotid artery remodeling and the intervention of telmisartan in Wistar rats. Methods 60 male Wistar rats were fed by normal (given 0.5% NaCl as control group), high salt (given 8% NaCl as high salt group) and high salt+telmisartan (given 8% NaCl+telmisartan as intervention group) diet for 24 weeks, respectively. At the end of experiment, the rats in high salt group were subdivided into high salt hypertension group and high salt normal blood pressure group by the tail-cuff artery pressure. The changes of histology and proliferation in carotid artery were observed by HE, Masson and immunohistochemical staining. TGF-β1, p-Smad2/3, Smad7, AngⅡ, AT1 and AT2 protein expression in carotid artery were determined by immunohistochemical staining. The level of aldosterone in carotid artery was mesured by radioimunoassay. Results Media thickeness (MT), ratio of media to lumen (MT/LD), proliferation index (PI), the collagen volume fraction, TGF-β1 and p-Smad2/3 were greater in high salt group than those in the control group (P<0.05), but telmisartan prevented these effects (P<0.05), Smad7 protein expression in high salt group was lower compared with control group (P<0.05), whereas higher in intervention group compared with high salt group (P<0.05). AngⅡ protein expression in high salt group and intervention group increased compared with control group (P<0.05). AT1 protein expression in high salt group increased compared with control group (P<0.05), but decreased in intervention group (P<0.05), high salt hypertension group and high salt normal blood pressure group was unchanged (P>0.05). AT2 protein expression in intervention group increased compared with high salt group and control group (P<0.05), control group, high salt hypertension group and high salt normal blood pressure group was unchanged (P>0.05). The aldosterone level in carotid arteries was greater in high salt hypertension group than that in control group and high salt normal blood pressure group (P<0.05), much greater than that in intervention group (P<0.01). Conclusions 8% NaCl diet can cause the carotid artery remodeling in Wistar rats, RAS and TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling.Telmisartan can prevent high salt-induced remodeling of carotid artery.

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陈剑玲,陈 涛,商黔惠,刘 婵,刘华庆.高盐饮食诱导Wistar大鼠颈动脉重塑的机制及替米沙坦的干预[J].中国动脉硬化杂志,2014,22(07):655~662.

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  • 收稿日期:2014-01-22
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