甘草次酸拮抗外源性皮质激素对肾上腺皮质反馈抑制的机理研究

The antagonization of glycyrrhetic acid(GA)to the feedback inhibition on adrenal cortex caused by exterioir glucocoticoid

应用非同位素斑点杂交及真彩色医学图像分析系统的定量分析等技术，观察了肾上腺皮质脂类含量及肾上腺组织中甾体激素合成过程中的关键酶－３β－羟脱氢酶Δ５－４异构酶（３β－ＨＳＤ）ｍＲＮＡ的表达，以期探讨甘草次酸拮抗外源性糖皮质激素对肾上腺皮质反馈抑制作用的机理。ＳＤ大鼠及阿霉素注射制成的肾病鼠接受甘草次酸和（或）地塞米松前后测定动物血浆皮质酮含量、肾上腺皮质束状带脂类含量及肾上腺３β－ＨＳＤｍＲ－ＮＡ的表达。结果发现地塞米松可导致以上三项指标下降，而甘草次酸能促进３β－ＨＳＤｍＲＮＡ的表达和增加脂类含量，且二者呈正相关（ｒ＝０．８４３１，Ｐ＜０．０５），脂类含量又与血浆皮质酮水平正相关（ｒ＝０．６８８２，Ｐ＜０．０１）。提示甘草次酸可促进肾上腺组织中３β－ＨＳＤｍＲＮＡ表达及增加脂类含量，使肾上腺皮质激紊的合成和分泌增加，从而拮抗外源性皮质激素所致的肾上腺皮质反馈抑制现象。

eedback inhibition of adrenal cortex isnoticed by exterior glucocoticoid treatment.Traditional Chinese herb glycyrrhizashowed some protective effect on adrenalcortex.This investigation aimed at explaringits mechanism.SD rats were devided into 6 groups: ①normal control; ② treated with GA;③ treat-ed with adriamycin;④ADR rats treatedwith GA; ⑤ ADR rats treated with dexam-ethason (Dx);and ⑥ ADR rats treated withDx and GA. To evaluate the antagonizingeffects, the plasma corticosterone was mea-sured, the lipid content of adrenal cortexand the expression of 3β-Hydrooxysteroiddehydrogenase ( 3β-HSD ) mRNA werequantitatively analysed.The results showed: ① A decrease ofplasma corticosteroid, lipid content and 3β-HSD mRNA expression were noticed in ratstreated with Dx.② GA showed a protectiveeffects on adrenal cortex suppressed by Dx.GA could stimulate the expresion of 3β-HSD mRNA and increase the lipid contentof adrenal cortex.There was a positive cor-relation between the expression of 3β-HSDmRNA and lipid content (r=0.8341, P<0.05), also the lipid content was closely re-lated to the level of plasma corticosterone (r=0.6882 ,P<0.01).Conclusion:The antagonizing effects ofGA to the feedback inhibition on adrenalcortex caused by Dx was through a stimula-tion of expression of 3β-HSD mRNA and anincreasing of the lipid content of adrenalcortx.