Yokozawa Takako, Yamabe Noriko, Cho Eun Ju, Nakagawa Takako, Oowada Shigeru
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Nephron Exp Nephrol. 2004;97(2):e38-48. doi: 10.1159/000078405.
To investigate the effects of Hachimi-jio-gan on diabetic nephropathy, we employed an animal model, rats subjected to sub-total nephrectomy followed by streptozotocin injection, and administered Hachimi-jio-gan orally at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. The administration of Hachimi-jio-gan reduced dose-dependently the elevated blood glucose and urinary protein excretion levels in rats with diabetic nephropathy over the experimental period, whereas it increased creatinine clearance significantly, suggesting that Hachimi-jio-gan would prevent or delay the progression of diabetic nephropathy. In addition, the serum glycosylated protein and urea nitrogen levels were markedly elevated in rats with diabetic nephropathy compared with normal rats, and were significantly reduced by the administration of Hachimi-jio-gan, whereas Hachimi-jio-gan reversed the decrease in the serum albumin level. The serum triglyceride and total cholesterol concentrations were reduced by Hachimi-jio-gan, implying that Hachimi-jio-gan would improve the metabolic disorder of lipids caused by diabetic nephropathy. Moreover, Hachimi-jio-gan inhibited lipid peroxidation in the serum and kidney, which suggests that Hachimi-jio-gan would ameliorate oxidative stress associated with diabetic nephropathy. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were also normalized by the administration of Hachimi-jio-gan through decreases in advanced glycation end-product formation and sorbitol levels in the kidney. Hachimi-jio-gan protected against the development of renal lesions, glomerular sclerosis, tubulointerstitial lesions, mesangial matrix expansion and arteriolar sclerosis, estimated by histopathological evaluation and scoring. This study suggests that Hachimi-jio-gan may be a novel therapeutic approach to improving diabetic nephropathy.
为研究八味地黄丸对糖尿病肾病的影响，我们采用了一种动物模型，即对大鼠进行次全肾切除术后注射链脲佐菌素，然后以50、100或200毫克/千克体重/天的剂量口服八味地黄丸，持续15周。在实验期间，八味地黄丸的给药剂量依赖性地降低了糖尿病肾病大鼠升高的血糖和尿蛋白排泄水平，同时显著增加了肌酐清除率，这表明八味地黄丸可以预防或延缓糖尿病肾病的进展。此外，与正常大鼠相比，糖尿病肾病大鼠的血清糖基化蛋白和尿素氮水平显著升高，而八味地黄丸的给药使其显著降低，同时八味地黄丸逆转了血清白蛋白水平的下降。八味地黄丸降低了血清甘油三酯和总胆固醇浓度，这意味着八味地黄丸可以改善糖尿病肾病引起的脂质代谢紊乱。此外，八味地黄丸抑制了血清和肾脏中的脂质过氧化，这表明八味地黄丸可以改善与糖尿病肾病相关的氧化应激。此外，通过降低肾脏中晚期糖基化终产物的形成和山梨醇水平，八味地黄丸的给药还使由于这种病理状况导致的葡萄糖依赖性代谢途径紊乱恢复正常。通过组织病理学评估和评分估计，八味地黄丸可预防肾损伤、肾小球硬化、肾小管间质损伤、系膜基质扩张和小动脉硬化的发生。本研究表明，八味地黄丸可能是一种改善糖尿病肾病的新型治疗方法。
