地黄中的梓醇对β肾上腺素受体cAMP系统的调整作用

Regulatory Action of Catalpol from Radix Rehmanniae on β-Adrenoceptor-cyclic AMP System

目的 :本室以往工作已证明地黄的滋阴作用与下调 β肾上腺素受体cAMP系统的功能有关 ,本文探讨地黄中的梓醇是否是地黄滋阴作用的有效活性成分。方法 :用溶剂提取结合硅胶低压柱层析法从鲜地黄中提取梓醇单体 ;用放射免疫法测定甲亢模型小鼠注射异丙基肾上腺素后血浆cAMP的含量变化 ;观察梓醇有无调整作用。结果 :注射异丙后 10min ,对照组血清cAMP上升到 70 0 pmol/ml以上 ,甲亢组显著高于对照组。自制的梓醇纯度在 97%以上 ,用药 6d使甲亢动物cAMP显著降低 ,剂量为 1 5 6mg/鼠 /d和 6mg/鼠 /d时 ,分别从(14 0 8± 5 6 8) pmol/ml和 (14 91± 4 86 ) pmol/ml降至 (978± 2 83) pmol/ml和 (10 70± 394 )pmol/ml( x±s) ,两种剂量的P值均 <0 0 5。结论 :梓醇能重现地黄水煎剂对β肾上腺素受体cAMP系统的调整作用 ,有效地下调甲亢动物对异丙的反应 ,提示梓醇是地黄滋阴作用的有效活性成分。

Objective It has been proved in previous works from this laboratory that the Yin tonic effect of water extract of Radix Rehmanniae is closely related to its down-regulation effect on β adrenoceptor-cyclic AMP system. The purpose of this work is to investigate whether catalpol from Radix Rehmanniae is the effective active component of this plant drug. Methods Catalpol was extracted from fresh Radix Rehmanniae by organic solvents and purified by low pressure silica gel column and recrystallization. Experimental mice were didvided into 4 groups. Three groups of hyperthyroid mouse models were prepared with subcutaneous injuection of T 3 and two of them were additionally fed oral catalpol at low and high dose respectively. One group receiving neither T 3 nor catalpol served as controls. Plasma cAMP levels in these mice were measured with RIA 10min after subcutanceous injuection of a single dose of isoproterenol. Results After injection of catalpol, the plasma cAMP content rose markedly to above 700pmol/ml in control mice while that of the hyperthyroid mice rose to a even higher levels. Simultaneous additional oral administration of catalpol with purity >97% for 6 days significantly lowered the affainable cAMP level in hyperthyroid mice. With catalpol dose of 1.56mg/mouse/d and 6.0mg/mouse/d, the plasma cAMP levels were 978±283pmol/ml and 1070±394pmol/ml respectively, the values in the group without catalpol being 1408±568pmol/ml and 1491±486pmol/ml, both P<0.05. Conclusion Catalol can repeat the regulatory effect of water extract of Radix Rehmanniae on β adrenoceptor-cyclic AMP system, that is, down regulate the response of hyperthyroid mice to isoproterenol. This result suggests that catalpol is an effective active component of the Yin tonic effect of Radix Rhmanniae.