Ma Yue, Fujimoto Makoto, Watari Hidetoshi, Kimura Mari, Shimada Yutaka
Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
J Nat Med. 2016 Apr;70(2):152-62. doi: 10.1007/s11418-015-0945-1. Epub 2015 Nov 7.
Antihypertensive treatment is highly important to prevent the progression of chronic kidney disease. Shichimotsukokato (SKT), a traditional Japanese medicine (i.e., Kampo formula), lowered systolic blood pressure (SBP) in experimental animal models of hypertension. However, its mechanism of action has not been fully elucidated. We investigated the potential renoprotective mechanism of SKT in spontaneously hypertensive rats (SHRs). Ten-week-old SHRs were randomly divided into four groups (six rats per group). In the SHR control group, the SBP increased remarkably during the 8-week experimental period. In the SHRs, SKT extract administered orally at a daily dose of 0.45 or 0.15 g/kg significantly suppressed the increase in SBP to the same extent as telmisartan administered orally at a daily dose of 0.01 g/kg. At the end of the experiment, blood, urine, and kidney cortex tissue samples were examined. The SKT treatment significantly decreased urinary albumin excretion to nearly the same level as the telmisartan treatment. A notable loss of chloride channel 5 (ClC-5), a chloride channel in the proximal renal tubules, occurred in the SHR control group. Thus, we concluded that SKT administration significantly ameliorated this decrease. The mechanism of SKT in reducing urinary albumin excretion is mediated, at least partly, by prevention of the loss of ClC-5 in the renal cortex of SHRs.
抗高血压治疗对于预防慢性肾脏病的进展至关重要。日本传统医学方剂七味白术散(SKT)在高血压实验动物模型中可降低收缩压(SBP)。然而,其作用机制尚未完全阐明。我们研究了SKT对自发性高血压大鼠(SHR)的潜在肾脏保护机制。将10周龄的SHR随机分为四组(每组6只大鼠)。在SHR对照组中,收缩压在8周实验期内显著升高。在SHR中,每日口服剂量为0.45或0.15 g/kg的SKT提取物与每日口服剂量为0.01 g/kg的替米沙坦一样,能显著抑制收缩压的升高。实验结束时,对血液、尿液和肾皮质组织样本进行了检测。SKT治疗显著降低尿白蛋白排泄,降至与替米沙坦治疗几乎相同的水平。在SHR对照组中,近端肾小管中的氯离子通道5(ClC-5)明显丢失。因此,我们得出结论,给予SKT可显著改善这种减少。SKT减少尿白蛋白排泄的机制至少部分是通过防止SHR肾皮质中ClC-5的丢失来介导的。