Sudo Hirokazu, Hirata Michinori, Kanada Hirotaka, Yorozu Keigo, Tashiro Yoshihito, Serizawa Ken-Ichi, Yogo Kenji, Kataoka Motoyuki, Moriguchi Yoshiyuki, Ishizuka Nobuhiko
Product Research Department, Chugai Pharmaceutical Co., Ltd., Japan.
J Pharmacol Sci. 2009 Sep;111(1):53-9. doi: 10.1254/jphs.09072fp. Epub 2009 Aug 29.
Recent clinical studies on chronic kidney disease (CKD) reported that renal dysfunction was a critical risk factor for cardiovascular events (CVE), which lead us to reconsider the effect of cardioprotective agents on the kidney. Glomerulonephritis, which is the major cause of CKD, is characterized by mesangial cell proliferation and extracellular matrix deposition. Nicorandil, a therapeutic drug for angina and acute heart failure, have been reported to show antiproliferative activity in mesangial cells. In this study, we first investigated the in vivo effects of nicorandil in anti-Thy1 nephritis rats. In male F344 rats, anti-Thy1 nephritis was induced by the injection of an anti-Thy1 antibody. From three days before induction, nicorandil (10, 30 mg/kg per day) was administered in the drinking water for 12 consecutive days. Anti-Thy1 nephritis resulted in a significant increase in proteinuria and glomerular mesangial cell proliferation. In nephritis rats, nicorandil (30 mg/kg per day) significantly suppressed increase in proteinuria, mesangial cell proliferation (the number of glomerular cell and glomerular area), and renal hypertrophy without affecting blood pressure. Nicorandil significantly prevented the overexpression of type I collagen, fibronectin, transforming growth factor (TGF)-beta, and platelet-derived growth factor (PDGF) mRNA. These results suggest that nicorandil may have renoprotective effects in mesangioproliferative glomerulonephritis.
近期关于慢性肾脏病（CKD）的临床研究报告称，肾功能不全是心血管事件（CVE）的关键危险因素，这促使我们重新审视心脏保护药物对肾脏的影响。肾小球肾炎是CKD的主要病因，其特征为系膜细胞增殖和细胞外基质沉积。尼可地尔是一种用于治疗心绞痛和急性心力衰竭的药物，据报道它在系膜细胞中具有抗增殖活性。在本研究中，我们首先研究了尼可地尔在抗Thy1肾炎大鼠体内的作用。在雄性F344大鼠中，通过注射抗Thy1抗体诱导抗Thy1肾炎。从诱导前三天开始，连续12天在饮用水中给予尼可地尔（每天10、30mg/kg）。抗Thy1肾炎导致蛋白尿和肾小球系膜细胞增殖显著增加。在肾炎大鼠中，尼可地尔（每天30mg/kg）显著抑制蛋白尿增加、系膜细胞增殖（肾小球细胞数量和肾小球面积）以及肾脏肥大，且不影响血压。尼可地尔显著阻止了I型胶原、纤连蛋白、转化生长因子（TGF）-β和血小板衍生生长因子（PDGF）mRNA的过度表达。这些结果表明，尼可地尔可能对系膜增生性肾小球肾炎具有肾脏保护作用。
