苦马豆素对山羊睾丸间质细胞StAR和P450scc表达的影响及其分子机制研究

疯草是危害我国西部草原畜牧业生产最为严重的毒草之一，其主要毒性成份苦马豆素（SW）可致公畜不育，严重影响家畜繁殖和畜种改良。研究发现，SW可使公畜睾酮（T）合成下降，但其作用机理尚不清楚。T的生成主要发生在睾丸间质细胞，StAR和P450scc是其合成途径的关键酶。由此推测，SW对T生成的抑制可能是通过下调StAR和P450scc的表达所致。为探讨SW对StAR和P450scc表达的影响及其分子调控机制，本项目拟建立萨能奶山羊疯草中毒模型，结合体外睾丸间质细胞原代培养实验，利用分子生物学相关技术，检测睾丸及间质细胞内StAR和P450scc的mRNA和蛋白表达水平，研究cAMP-PKA-ERK1/2信号通路、转录因子及表遗传修饰对其调控作用，从而阐明SW调控StAR和P450scc表达的分子机制。预期结果将揭示疯草所致雄性不育的分子机制，也为疯草中毒防治奠定理论基础。

Locoweed is one of the most serious poisonous weeds, harming livestock production in the grasslands in western China. Swainsonine (SW) is the main toxic component in locoweed, which can induce sterility in male livestock, seriously affecting livestock breeding and improvement. As has been revealed in some studies, SW reduced testosterone (T) biosynthesis in male livestock, but the molecular mechanisms are still poorly understood. T is synthesized primarily in Leydig cells, and catalyzed by the key enzymes StAR and P450scc. It can therefore be speculated that SW may decrease T production by lowering the expression of StAR and P450scc. In order to investigate the effect of SW on the expression of StAR and P450scc and the underlying molecular mechanisms, we use saanen and the primary Leydig cells as model, to study the expression of StAR and P450scc, and explore the underlying regulatory effects of cAMP-PKA-ERK1/2 signal pathway, transcription factors and epigenetic modification. Our results are expected to reveal the molecular mechanisms of locoweed induced male sterility, and to give a theoretical reference for the prevention and treatment of locoism.