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

1)采用运动分析仪研究了汉布药新武托对豚鼠心肌细胞收缩活性的急性影响。Shinbuto （3 ~ 5 mg/ml）可使肌细胞的收缩幅度增加56 ~ 369%，呈浓度依赖性。然而，在不同条件下得到的结果并不一致。2)长期给药心武对小鼠心脏和肾脏基因表达的影响。心脏中约50个基因和肾脏中约100个基因表现出明显的变化。一种凋亡相关基因在心脏中表达增加，但在肾脏中表达减少。3)以高血压心力衰竭模型大鼠、自发性高血压大鼠（SHR）为实验对象，观察长期给药心武对患病动物的影响。虽然对照动物（SHR）没有表现出任何心力衰竭的症状，也没有尿钠肽的增加，但Shinbuto的五种成分中的每一种都有单独抑制SHR血压的倾向，而其他三种成分对血压没有任何影响。各成分改变了热休克蛋白、肾素-血管紧张素系统、钾离子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。给药后正常小鼠的基因表达发生了显著变化，而患病小鼠的基因表达无显著变化。这些发现表明，一种汉布药Shinbuto的效果不仅因物种而异，而且因病理状况而异。

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.