慢性肾衰竭大鼠主动脉弹性功能与血管基质金属蛋白酶2表达及钙化间的关系
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河北省自然科学基金(H2012206157)


The Association Between Aortic Matrix Metalloproteinase-2 and Vascular Stiffness in Uremic Rats
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    摘要:

    目的 探讨主动脉基质金属蛋白酶2(MMP-2)在慢性肾衰竭大鼠主动脉弹性功能变化中的作用及机制。方法 将20只大鼠随机分为正常对照组、慢性肾衰竭组、慢性肾衰竭血管钙化组。8周造模成功后测量大鼠主动脉脉搏波传导速度(PWV),分别用逆转录-聚合酶链反应和免疫组织化学方法检测大鼠主动脉核心结合因子α1(Cbfα1)及MMP-2 mRNA和蛋白的表达。EVG染色方法检测主动脉弹性纤维的改变。结果 慢性肾衰竭血管钙化组PWV值和主动脉Cbfα1、MMP-2的mRNA及蛋白表达均高于慢性肾衰竭组及正常对照组(P<0.05),PWV与主动脉MMP-2表达呈正相关(r=0.754,P=0.02)。结论 慢性肾衰竭大鼠血管弹性功能下降的可能机制之一是血管壁MMP-2表达升高导致弹性蛋白降解,同时后期的血管钙化也参与其中。

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    Aim To explore the relationship between uremia rats aortic stiffness and expression of matrix metalloproteinase-2 (MMP-2) in aorta and the mechanism involved. Methods 20 rats were divided into three groups randomly, as normal control group, chronic renal failure group and chronic kidney failure group with vascular calcification. Normal control group (methyl cellulose), chronic renal failure group (methyl cellulose+adenine sulphate), chronic renal failure group with vascular calcification (adenine sulphate+calcitriol). The aortic pulse wave velocity (PWV) was measured after 8 weeks, expression of core binding factor alpha 1 (Cbfα1) and MMP-2 mRNA were determined by reverse transcription polymerase chain reaction (RT-PCR) and MMP-2 protein was detected by immunohistochemistry. Von Kossa was used to test the calcification of aorta and quantified by aortic calcium content. The alteration of aortic stiffness was tested by Elastica Van Gieson (EVG). Results Aortic PWV, expression of aorta Cbfα1, MMP-2 mRNA and protein, aortic calcium content in chronic renal failure group with vascular calcification are all higher than those in chronic renal failure group (P<0.05).Aortic PWV, expression of aorta Cbfα1, MMP-2 mRNA and protein in chronic renal failure group are higher than those in normal control group (P<0.05). Aortic PWV shows a positive correlation to the expression of MMP-2 in aorta (r=0.754, P=0.02). Conclusion One of the mechanisms of decreased vascular elasticity function in rats with chronic kidney disease is elastin degradation caused by increasing expression of MMP-2 in the artery wall, while the late vascular calcification is also involved.

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张俊霞,徐金升,朱荣芳,白亚玲,张胜雷,崔立文,张慧然,周 薇.慢性肾衰竭大鼠主动脉弹性功能与血管基质金属蛋白酶2表达及钙化间的关系[J].中国动脉硬化杂志,2014,22(02):115~120.

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  • 收稿日期:2013-07-05
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