Cellular and molecular pharmacological study of the mechanisms underlying the effects of Kanpo medicine.

1)用运动分析仪研究了Kampo药新武藤对豚鼠心肌细胞收缩活动的急性影响。辛布托(3-5 mg/ml)可使心肌细胞收缩幅度增加56-369%，且呈浓度依赖性。然而，不同条件下的结果并不一致。2)长期给药对小鼠心脏和肾脏基因表达的影响。心脏中约50个基因和肾脏中表达的约100个基因发生了显著变化。3)在高血压心力衰竭模型大鼠、自发性高血压大鼠(SHR)模型上，观察了长期给药对患病动物的影响。尽管对照动物(SHR)没有表现出任何心力衰竭的症状，也没有钠尿肽的增加，但信步的五种成分中的每一种都有降低SHR血压的趋势，而其他三种成分对血压没有任何影响。新武藤各成分均可改变热休克蛋白、肾素-血管紧张素系统、钾离子通道和钙离子通道相关基因的表达。这些基因似乎与高血压有关。给正常小鼠服用新武藤后，基因表达发生了显著变化，但在这些患病的大鼠中没有表现出任何明显的变化。这些发现表明，新武藤的作用不仅因物种而异，而且因病理条件而异。

1) The acute effects of Shinbuto, a Kampo medicine on the contraction activity of guinea-pig cardiac myocytes were studied using a motion analyzer. Shinbuto (3-5 mg/ml) tended to increase the contractile amplitude of myocytes by 56-369% in a concentration dependent manner. However, results obtained under different conditions were inconsistent.2) The effect of long-term Shinbuto administration on heart and renal genes expression in mice. About 50 genes in the heart and about 100 genes expressed in the kidney showed marked changes. One apoptosis-related gene showed increased expression in the heart, but a decrease in the kidney.3) The effect of long-term Shinbuto administration to diseased animals was examined in hypertensive heart failure model rats, spontaneously hypertensive rats (SHR). Although control animals (SHR) did not show any symptoms of heart failure nor an increase in natriuretic peptide, each of two of the five ingredients of Shinbuto individually tended to suppress the blood pressure in SHR, while the other three did not show any effect on blood pressure. Each ingredient of Shinbuto changed the expressions of genes related to heat shock protein, renin-angiotensin system, potassium ion and calcium ion channels. These genes seem to be related to hypertension. Gene expressions changed markedly following Shinbuto administration to normal mice, but did not show any remarkable change in these diseased rats.These findings suggest that the effects of Shinbuto, a Kampo medicine vary not only with species, but also with pathological conditions.