Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
Evid Based Complement Alternat Med. 2012;2012:587902. doi: 10.1155/2012/587902. Epub 2012 Nov 29.
Two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) were selected to examine their actions in nephrectomized rats. Each prescription was given orally to rats for 10 weeks after the excision of five-sixths of their kidney volumes, and its effect was compared with non-nephrectomized and normal rats. Rats given Hachimi-jio-gan and Bakumi-jio-gan showed an improvement of renal functional parameters such as serum urea nitrogen, creatinine, creatinine clearance, and urinary protein. The nephrectomized rats exhibited the up-regulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, c-Jun N-terminal kinase (JNK), phosphor-JNK, c-Jun, transforming growth factor-β(1), nuclear factor-kappa B, cyclooxygenase-2, inducible nitric oxide synthase, monocyte chemotactic protein-1, intracellular adhesion molecule-1, Bax, cytochrome c, and caspase-3, and down-regulation of NF-E2-related factor 2, heme oxygenase-1, and survivin; however, Bakumi-jio-gan administration acts as a regulator in inflammatory reactions caused by oxidative stress in renal failure. Moreover, the JNK pathway and apoptosis-related protein expressions, Bax, caspase-3, and survivin, were ameliorated to the normal levels by Hachimi-jio-gan administration. The development of renal lesions, glomerular sclerosis, tubulointerstitial damage, and arteriolar sclerotic lesions, estimated by histopathological evaluation and scoring, was strong in the groups administered Hachimi-jio-gan rather than Bakumi-jio-gan. This study suggests that Rokumi-jio-gan-containing prescriptions play a protective role in the progression of renal failure.
选择了两种含有八味地黄丸的方剂（八味地黄丸和八味当归丸），以研究其在肾切除大鼠中的作用。在切除五分之六肾体积后，将每种方剂分别给予大鼠口服 10 周，并与未肾切除和正常大鼠进行比较。给予八味地黄丸和八味当归丸的大鼠，其肾功能参数如血清尿素氮、肌酐、肌酐清除率和尿蛋白均有改善。肾切除大鼠的烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基、c-Jun N 末端激酶（JNK）、磷酸化 JNK、c-Jun、转化生长因子-β(1)、核因子-κB、环氧化酶-2、诱导型一氧化氮合酶、单核细胞趋化蛋白-1、细胞间黏附分子-1、Bax、细胞色素 c 和半胱天冬酶-3 的表达上调，NF-E2 相关因子 2、血红素加氧酶-1 和生存素的表达下调；然而，八味当归丸的作用是调节肾衰氧化应激引起的炎症反应。此外，八味地黄丸可改善 JNK 通路和凋亡相关蛋白表达，如 Bax、半胱天冬酶-3 和生存素，使其恢复到正常水平。通过组织病理学评估和评分，八味地黄丸组的肾小球硬化、肾小管间质损伤和小动脉粥样硬化病变的发展比八味当归丸组更为严重。本研究表明，含有八味地黄丸的方剂在肾衰竭的进展中发挥保护作用。
