基于PA-1/hESCs敏感基因联合人胎盘屏障体外模型建立中药胚胎毒性评价体系的研究

中医药对妊娠病及妊娠合并症疗效显著，因缺乏符合中医药特点的胚胎毒性评价方法，使中药的应用受到制约。多能基因和三胚层标记基因在胚胎发育中较成体细胞标记基因更早表达，对随后组织器官的发育有重要影响。受试物对胚胎干细胞多能基因和三胚层标记基因表达的影响可作为评价受试物胚胎毒性的指标。课题组前期证明了PA-1具有胚胎干细胞特性。妊娠期药物只有透过胎盘屏障才可能对胚胎产生影响，课题组前期建立了人胎盘屏障体外模型。本课题拟将一系列已知有/无胚胎毒性受试物的Cmax作用于PA-1/hESCs，通过多能基因和三胚层标记基因的表达，筛选敏感基因，并确定胚胎毒性的判定阈值，建立基于PA-1/hESCs敏感基因的胚胎毒性评价模型。联合应用人胎盘屏障体外模型，建立符合中医药特点的妊娠期应用中药安全性评价体系，评价示范药黄芩、补骨脂、天南星、双黄连的胚胎毒性，测试该体系的可靠性和实用性，促进中医药与国际接轨。

The effect of traditional Chinese medicine on pregnancy diseases and pregnancy complications is significant. The application of traditional Chinese medicine is restricted due to the lack of evaluation method of embryonic toxicity which accords with the traditional Chinese medicine. The expression of pluripotent genes and three germ layers marker genes is earlier than that of adult cell marker genes in the development of embryo, which has an important influence on the development of tissues and organs. The effects of the substance on the expression of pluripotent genes and three germ layers marker genes of embryonic stem cells can be used as end points to evaluate the embryonic toxicity of the substance. It was proved that PA-1 has the characteristics of embryonic stem cells. Only through the placental barrier can pregnancy drugs have an effect on embryos. Therefore, Our group established the human placental barrier model. In this study, Cmax of a series of known embryonic toxic substances was applied to PA-1 / hESCs, Through the expression of pluripotent genes and three germ layer marker genes, sensitive genes are screened, and the threshold is determined. A embryo toxicity model based on PA-1 / hESCs sensitive genes is established. Combined with the human placenta barrier model, a safety evaluation system to evaluate the embryonic toxicity of traditional Chinese medicine in pregnancy was established. By evaluate the embryonic toxicity of Scutellaria baicalensis Georgi, psoralen, tiannanxing and Shuanghuanglian, to test the reliability and practicability of the system, and to promote the integration of traditional Chinese medicine with the world.