淫羊藿总黄酮拮抗皮质酮大鼠肾上腺皮质细胞凋亡的研究

目的:研究淫洋藿总黄酮(EF)拮抗糖皮质激素副作用,保护肾上腺皮质功能的机制。方法:采用肾上腺重量指数评价EF应用后萎缩的肾上腺皮质恢复情况;分离肾上腺细胞,流式细胞仪检测细胞凋亡率;并用末端脱氧核苷酸转移酶介导缺口末端标记法(TUNEL)原位检测细胞凋亡;用大鼠全基因组表达谱芯片检测凋亡相关基因表达。结果:与正常组相比,皮质酮组肾上腺重量指数显著下降,肾上腺细胞凋亡率明显上升,P<0.05;EF治疗后,肾上腺重量指数升高,细胞凋亡率明显下降,P<0.05。TUNEL显示正常组、皮质酮组、EF组每张切片平均凋亡细胞数分别为4.67±1.53、70.67±9.29、18.67±7.64;基因芯片发现正常大鼠肾上腺有53个凋亡相关基因表达,其中39个具有促凋亡活性,14个基因具有抗凋亡活性,促凋亡基因和抗凋亡基因组成了一个网络,皮质酮使3个具有抗凋亡活性的基因下调,EF治疗使具有抗凋亡活性AMP激活蛋白激酶α1催化亚单位基因和丝裂原激活蛋白激酶8相互作用蛋白基因显著上调。结论:EF拮抗皮质酮诱导的大鼠肾上腺皮质过度凋亡是其拮抗糖皮质激素对HPA轴的抑制,保护肾上腺皮质功能的机制。

Inhibition Effect of Epimedium Flavonoids on Adrenocortical Cell Apoptosis Induced by Corticorsterone

Objective:To identify the underlying mechanisms of adrenal function recovery by Epimedium Flavonoids(EF) in HPA-axis inibited rats.Methods: Adrenal weight index was used to evaluate the recovery of adrenal atrophy induced by corticosterone treatment.Apoptotic rate was obtained from isolated adrenal cells with flowcytometry.TUNEL was employed to display apoptotic cells in situ.Apoptosis related genes mRNA expression was detected with DNA microarray.Results:Compared to control,corticosterone group had decreased adrenal weight index and increased apoptotic rate(P<0.05),and reversed by EF(P<0.05);the average apoptotic cell number was 5,71,19 from control, corticostrone group and EF group respectively.39 pro-apoptotic and 14 anti-apoptotic genes consisting of a molecular network was constitutively expressed in adrenal gland of control.Coticosterone down-regulated 3 anti-apoptotic gene.After treatment with EF,2 anti-apoptotic gene named AMP-activated protein kinase alpha 1 catalytic subunit and mitogen activated protein kinase 8 interacting protein were up-regulated.Conclusion: EF' inhibition of adrenocortical cell apoptosis induced by corticosterone contributes to adrenal function recovery.