Drug discovery for improvement of chronic kidney disease and cardiovascular disease.
Drug discovery for improvement of chronic kidney disease and cardiovascular disease.
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改善慢性肾脏疾病和心血管疾病的药物发现。
DOI：
10.1248/yakushi.131.1347
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
K. Ishizawa
中科院分区：
文献类型：
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作者：
K. Ishizawa
慢性肾脏病（CKD）已日益被公认为全球主要的公共卫生问题。最近的研究表明，CKD是心血管疾病（CVD）发生的独立危险因素。活性氧（reactive oxygen species，ROS）是由氧化还原作用产生的，是调节血管平滑肌细胞（vascular smooth muscle cells，VSMC）和肾小球系膜细胞（mesangial cells，MC）信号转导的重要化学介质。研究表明，ROS产生的增加可能与CVD和CKD的风险有关。此外，ROS介导多种细胞中的丝裂原活化蛋白（MAP）激酶、细胞外信号调节激酶1/2、c-Jun N-末端激酶、p38和大MAP激酶1的活化，导致基因表达的变化。控制氧化应激和ROS介导的信号分子（包括MAP激酶）的改变可能为CKD和CVD提供新的治疗策略。本文主要就肾素-血管紧张素-醛固酮系统阻断剂、联苯双酯和脂联素对VSMC和MC的药理作用进行综述。此外，我们还回顾了一种可能的新型抗氧化应激药物，以改善CKD和CVD的数据。
Chronic kidney disease (CKD) has been increasingly recognized as a major public health problem in the world. Recent studies have showed that CKD is an independent risk factor for the occurrence of cardiovascular disease (CVD). Reactive oxygen species (ROS), generated by reduction-oxidation actions, have been generated by reduction-oxidation actions, recognized as the important chemical mediators that regulate signal transduction in various cells including vascular smooth muscle cells (VSMC) and mesangial cells (MC). It has been showed that increase in ROS generation may relate to a risk for CVD and CKD. In addition, ROS mediate activation of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, p38, and big MAP kinase 1, in various cells leading to change in gene expressions. Control of the oxidative stress and ROS-mediated alterations of signaling molecules including MAP kinases may provide new therapeutic strategy against CKD and CVD. In this review, we summarize mainly our data regarding the pharmacological effects of renin-angiotensin-aldosterone system blockers, bioflavonoids and adiponectin in VSMC and MC. Also we review the data on a possible new class drug against oxidative stress to improve CKD and CVD.