从维生素D轴探讨肾精亏虚证大鼠肾上腺皮质类固醇生成异常及淫羊藿苷干预机制

Current testing strategies to assess the kidney essence deficiency syndrome were corticosterone, sex hormone secretion disorder.There have omitted examination of the adrenal gland and do not adequately cover the process of steroidogenesis. Steroidogenesis is critical for adrenocortical function as well as that of the testes and ovaries. Hypoadrenocorticism is a common pathophysiological of kidney essence deficiency. Preliminary studies indicate that steroidogenesis disrupting is relevant vitamin D deficiency in kidney essence deficiency rat model. We present the science hypothesis :Vitamin D is the material basis of kidney essence, and kidney tonifying herbs of icariin can regulate the expression of adrenal cortex steroidogenesis and related synthetase gene through vitamin D axis.This project intends to discuss the changes of vitamin D axis and steroidogenesis by icariin in kidney essence deficiency rats model. And use of RNA interference ( siRNA ) knockout of vitamin D receptor of H295R cells, study steroidogenesis enzyme gene expression and hormone levels and icariin on the impact of it.Revealed the relationship between vitamin D deficiency and kidney essence deficiency syndrome. Explicit the molecular mechanism of icariin in regulate the steroidogenesis by vitamin D axis.

现代肾本质研究揭示肾虚证表现皮质酮、性激素分泌紊乱。肾上腺皮质同睾丸和卵巢一样，是类固醇激素生成的重要场所。肾上腺皮质功能减退是肾虚证的共同病理基础。但现代研究没有从整体观念探讨肾上腺皮质类固醇激素生成在肾虚中的功能。基于文献及前期研究表明维生素D与肾上腺皮质类固醇激素生成密切相关，维生素D缺乏与肾精亏虚之间病理生理联系密切相关，由此提出：维生素D是"肾藏精"的物质基础，补肾药淫羊藿苷作用于维生素D轴调节肾上腺皮质类固醇激素分泌及相关合成酶基因表达的科学假说。本课题拟从动物实验探讨淫羊藿苷干预肾虚大鼠前后维生素D轴与肾上腺皮质类固醇激素分泌的变化。并运用RNA干扰技术（siRNA）敲除H295R细胞维生素D受体，观察淫羊藿苷干预前后类固醇激素生成相关酶基因表达和激素水平。揭示维生素D缺乏与肾精亏虚证候属性之间的联系，明确"肾不藏精" 客观物质基础和调控规律及淫羊藿苷作用的分子机制。

现代肾本质研究揭示肾虚证表现皮质酮、性激素分泌紊乱。肾上腺皮质同睾丸和卵巢一样，是类固醇激素生成的重要场所。肾上腺皮质功能减退是肾虚证的共同病理基础。基于维生素D与肾上腺皮质类固醇激素生成密切相关。本课题通过比较维生素D缺乏肾虚大鼠及衰老肾虚大鼠模型，发现二种模型存在类固醇合成障碍。结合动物实验及细胞实验探讨了淫羊藿苷作用于肾虚大鼠肾上腺皮质及H295R细胞类固醇激素合成的机制。为淫羊藿苷的作用分子机制进行探讨，为中医补肾药物作用的微观机制提供一个新的靶点。培养研究生4名。国家中医药管理局中医药传承与创新“百千万”人才工程（岐黄工程）人选1人。发表中文核心期刊10篇。