右归配方颗粒对肾阳虚型体外受精－胚胎移植患者卵巢颗粒细胞基因表达谱的影响

目的从基因组学角度探讨温肾阳中药对肾阳虚型体外受精-胚胎移植（in vitro fertilizationembryo transfer,IVF-ET）患者卵巢颗粒细胞基因表达谱的影响。方法 72例行IVF治疗的肾阳虚患者按照随机数字表法分为治疗组（36例）和对照组（36例）,治疗组服用右归配方颗粒联合促性腺激素（gonadotropin,Gn）,对照组服用安慰剂联合Gn,两组均在IVF治疗前连续用药3个周期。两组采用超排卵长方案治疗后,行穿刺取卵术。利用基因高通量测序技术对两组患者卵巢颗粒细胞基因表达谱进行分析,研究两组患者基因表达谱的差异,并对差异基因行基因本体（gene ontology,GO）分析和京东基因与基因组百科全书（kyoto encyclopedia of genes and genomes,KEGG）通路分析。结果通过对两组患者卵巢颗粒细胞基因表达谱的分析,共筛选到391个差异表达基因,其中上调基因238个,下调基因153个。差异表达基因参与的富集的分子功能是：与细胞增殖、凋亡有关的细胞周期调节蛋白,蛋白质泛素化,微管、微丝等细胞骨架的构建,线粒体及能量相关功能的因子,激素合成调节因子等;参与的通路是能量代谢通路和转化生长因子-β（transforming growth factor-β,TGF-β）信号通路。结论两组患者卵巢颗粒细胞基因表达谱存在明显差异,差异表达基因所涉及的生物学过程与肾阳虚导致的生殖细胞增殖、凋亡紊乱,线粒体产生能量过程受阻等有相关性。

Effect of Yougui Formula Granule on Ovarian Granulosa Cells Gene Expression Profiles in IVF Patients of Shen Yang Deficiency Syndrome

Objective To observe the effect of Yougui Formula Granule（ YFG） on ovarian granulosa cells gene expression profiles in in vitro fertilization-embryo transfer（ IVF-ET） patients of Shen yang deficiency syndrome（ SYDS） from the viewpoint of genomics. Methods Totally 72 infertility patients undergoing IVF-ET were randomly assigned to the treatment group and the control group according to random digit table,36 in each group. Patients in the treatment group took YFG combined gonadotropin（ Gn）,while those in the control group took placebos combined Gn. All medication lasted for 3 menstrual cycles before IVF. With high-throughput gene sequencing technology,gene expression profiles of ovarian granulosa cells in the two groups were analyzed to explore the difference by gene ontology（ GO） enrichment analysis and kyoto encyclopedia of genes and genomes（ KEGG） pathway analysis. Results Ovarian granulosa cell gene expression profiles from the follicular fluid showed,when compared with the control group,391 differential genes were found in the syndrome-control group,153down-regulated and 238 up-regulated. Enrichment of differentially expressed cellular location and molecular function of genes involved cell proliferation and apoptosis associated cyclin,protein ubiquitination,construction of microtubules and microfila-ment,mitochondrial function and energy-related factors,regulatory factors for hormone synthesis. Participated pathways involved energy metabolism pathway and transforming growth factor-β（ TGF-β） signaling pathway. Conclusions There existed significant difference in gene expression profiles of ovarian granulosa cells between the treatment group and the control group. Differentially expressed genes involved in biological processes correlates with Shen yang deficiency induced proliferation of germ cells,confused apoptosis,and hindered process during which mitochondria produced energy.