Hirasawa Yasushi, Matsui Yukari, Yamane Kazusuke, Yabuki Shin-Ya, Kawasaki Yukiko, Toyoshi Tohru, Kyuki Kohei, Ito Masanori, Sakai Takayuki, Nagamatsu Tadashi
Department of Pharmacobiology and Therapeutics, Faculty of Pharmacy, Meijo University, Gifu, Japan.
Exp Anim. 2008 Oct;57(5):423-32. doi: 10.1538/expanim.57.423.
Medications to treat hyperglycemia and hyperinsulinemia are expected to inhibit the accumulation of advanced glycation end-products in the diabetic kidney and improve renal function by inhibiting oxidative reactions. In this study, we examined the effect of pioglitazone, an insulin sensitizer, on diabetic nephropathy. Feed containing pioglitazone at 0.01 or 0.02% was given to Zucker-fatty rats for 27 weeks. Pioglitazone reduced plasma glucose, plasma insulin, and blood HbAlc levels. It also decreased plasma total cholesterol, triglyceride, phospholipid and cystatin C levels and inhibited the increase in urine of 8-hydroxydeoxyguanosine and in plasma of malondialdehyde. In the histopathological examinations, pioglitazone inhibited diffusive or nodular thickening of the mesangial matrix, atrophy of the proximal convoluted tubule, thickening of the basement membrane of the tubule, and mild cellular infiltration (mostly small lymphocytes) in the stroma. Furthermore, pioglitazone inhibited the mRNA expression of the receptor for advanced glycation end-products (RAGE) and that of transforming growth factor-beta. Long-term administration of pioglitazone improved hyperglycemia lipid profiles, hypercholesterolemia, and hyperinsulinemia and had a protective effect on diabetic nephropathy in Zucker-fatty rats.
用于治疗高血糖和高胰岛素血症的药物有望抑制糖尿病肾病中晚期糖基化终产物的积累，并通过抑制氧化反应改善肾功能。在本研究中，我们检测了胰岛素增敏剂吡格列酮对糖尿病肾病的影响。将含有0.01%或0.02%吡格列酮的饲料喂给Zucker肥胖大鼠27周。吡格列酮降低了血浆葡萄糖、血浆胰岛素和血液糖化血红蛋白水平。它还降低了血浆总胆固醇、甘油三酯、磷脂和胱抑素C水平，并抑制了尿中8-羟基脱氧鸟苷和血浆中丙二醛的增加。在组织病理学检查中，吡格列酮抑制了系膜基质的弥漫性或结节性增厚、近端曲管萎缩、肾小管基底膜增厚以及间质中的轻度细胞浸润（主要是小淋巴细胞）。此外，吡格列酮抑制了晚期糖基化终产物受体（RAGE）和转化生长因子-β的mRNA表达。长期给予吡格列酮可改善高血糖血脂谱、高胆固醇血症和高胰岛素血症，并对Zucker肥胖大鼠的糖尿病肾病具有保护作用。
