Felodipine Reduces Cardiac Expression of IL-18 and Perivascular Fibrosis in Fructose-Fed Rats
Felodipine Reduces Cardiac Expression of IL-18 and Perivascular Fibrosis in Fructose-Fed Rats
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DOI：
10.2119/2008-00024.xing
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发表时间：
2008-07
影响因子：
5.7
通讯作者：
S. Xing;H. Tan;X. Bi;M. Zhong;Yun Zhang;Wei Zhang
中科院分区：
文献类型：
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作者：
S. Xing;H. Tan;X. Bi;M. Zhong;Yun Zhang;Wei Zhang
代谢综合征与大血管和微血管冠心病、心肌病和炎症状态升高有关。为了确定代谢综合征相关的血清和心脏组织中炎症细胞因子白介素-18 （IL-18）的升高及其潜在的后遗症是否可以从药理学上减弱，我们研究了果糖喂养的大鼠。果糖喂养的大鼠表现出收缩压（SBP）、体重、心脏重量、左心室重量和血胰岛素的增加。大鼠血清IL-18水平也显著升高。这些变化与对照组大鼠相比有显著差异。通过免疫组织化学分析和实时聚合酶链反应，果糖喂养的大鼠冠状动脉周围血管周围纤维化明显，并伴有IL-18的平行升高。非洛地平降低了血清IL-18和心脏IL-18 mRNA水平升高以及冠状动脉血管周围纤维化。因此，代谢综合征患者血清和心脏组织中IL-18的升高可能与冠状动脉血管周围纤维化有关；非洛地平可减轻炎症和纤维化过程。
Metabolic syndrome is associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathy, and elevated inflammatory status. To determine whether metabolic syndrome-associated elevation of the inflammatory cytokine interleukin-18 (IL-18) in serum and cardiac tissue, and its potential sequelae could be attenuated pharmacologically, we studied fructose-fed rats. The fructose-fed rats exhibited increases in systolic blood pressure (SBP), body weight, heart weight, left ventricular weight, and blood insulin. Serum IL-18 levels in these rats were also elevated significantly. These changes were significantly different compared to those in control rats. Perivascular fibrosis around coronary arterioles was evident in the fructose-fed rats, accompanied by a paralleled increase in IL-18 by immunohistochemical analysis and real time polymerase chain reaction. Felodipine attenuated the increased levels in serum IL-18 and cardiac IL-18 mRNA as well as coronary perivascular fibrosis. Thus, augmented IL-18 in serum and cardiac tissue in metabolic syndrome may contribute to the coronary perivascular fibrosis; felodipine administration can attenuate the inflammatory and fibrosis process.