梓醇对β肾上腺素受体及M胆碱受体失平衡的双向调节作用

Dual direction regulatory effect of catalpol on β-adrenergic receptor and M-cholinergic receptor

目的探讨地黄中的梓醇是否为地黄滋阴作用的有效活性成分。方法用放射配基结合分析单点法,测定甲亢模型小鼠大脑β肾上腺素受体(β受体)密度和自然衰老小鼠大脑M胆碱受体(M受体)密度,并以电迷路法考察自然衰老小鼠行为学的改变。结果甲亢组脑β受体密度显著高于对照组,分别为(20.9±7.2)和(15.7±5.2)fmol/mg蛋白,梓醇治疗的两组动物显著低于甲亢组,分别为(18.6±7.2)和(18.4±5.6)fmol/mg蛋白(P<0.05)。自然衰老模型组用Y电迷路测得的学习7 d后正确率仅为70%,喂服两种剂量的梓醇8周后,学习7 d后正确率达到90%以上,与老年对照组比较均有显著提高(P<0.01),与喂服阳性对照药知母皂甙元组正确率相仿。与此同时,老年对照组、知母皂甙元组、小剂量和大剂量梓醇组的脑M受体密度分别为(639±134)、(739±181)、(754±121)和(830±156)fmol/mg蛋白,表明3个用药组与老年对照组比较,均能显著提高脑M受体(P<0.05)。结论梓醇能重现地黄水煎剂对β肾上腺素受体及M胆碱受体失平衡的双向调节作用,提示梓醇是地黄滋阴作用的有效活性成分。

Objective To investigate whether catalpol is the active component responsible for the Yin tonic effect of Radix Rehmanniae. Methods Young NH mice were injected with triiodothyronine to produce the hyperthyroidism model, while old mice were used as the model of natural aging. The single point radioligand binding assay was carried out to determine the β-adrenergic receptor density and M-cholinergic receptor density. The learning ability （short term memory） was determined by the Y-maze avoidance test. Results In the β-adrenergic receptor experiment, the densities were （15.7 ±5.2） and （20.9 ±7.2 ） fmol/mg protein in normal control group and in T3 control group （P 〈 0.01 ）. In the two catalpol treatment groups, the receptor density dropped to （18.6 ± 7.2 ） and （18.4 ± 5.6 ） fmol/mg protein in comparison with the T3 control group （P 〈 0.05）. In the naturally aged mice group, on the seventh day of training the Y-maze test revealed that the learning ability （short time memory） was only 70% correct. After 8 weeks of two doses of catalpol, the learning ability reached 90% . It was significantly higher than aged control group （ P 〈 0.01 ） and similar to sarsasapogenin group. Radioligand binding assay with 3 H-QNB showed that the M-cholinergic receptor density of the aged mice was significantly increased by sarsasapogenin and the two doses of catalpol as compared with aged control, being （639 ± 134） fmol/mg for aged control, （ 739 ± 181 ） fmol/mg for sarasasapogenin, （754 ±121） and （830 ±156） fmol/mg for the two doses of catalpol （P〈0.05）. Conclusion Catalpol can repeat the regulatory effect of water extract of Radix Rehmanniae in down-regulating the β-adrenergic receptor and up-regulating the M-cholinergic receptor, suggesting that catalpol is an effective component responsible for the Yin tonic effect of Radix Rehmanniae.