子宫平滑肌瘤以平滑肌细胞由分化型向增殖型转换为主要病理特征，雌激素和雌激素受体α（ERα）在促进子宫平滑肌细胞向增殖型转化并成瘤中发挥重要作用，但机制有待阐明。Myocardin是血清反应因子（SRF）辅助转录因子，通过与平滑肌细胞分化基因启动子上的CarG序列结合，强力激活其表达，促进细胞分化。我们先前研究首次证明，ERα抑制Myocardin对平滑肌细胞分化基因激活，同时也抑制Myocardin表达。本研究将在此基础上，利用各种细胞和分子生物学技术和方法，证明雌激素和ERα能够抑制细胞分化，促进增殖，其机制包括抑制Myocardin依赖的细胞分化和细胞周期抑制基因；抑制Myocardin自身的启动子激活等。最终，将在分子-细胞-整体水平上，阐明雌激素和ERα促发子宫平滑肌瘤的最新分子机制，揭示其病理生理规律。为子宫平滑肌瘤的防治和新药研发或基因治疗提供重要的理论依据。

One of the main pathological features of is smooth muscle cells from differentiated to proliferative change. Estrogen and estrogen receptor α (of ERα) play an important role in promoting uterine smooth muscle cell into proliferation type conversion and in form and development in uterine leiomyoma, but the mechanism remains unknown. Myocardin is a serum response factor (SRF) co-transcription factors, binding on CarG sequence of the promoters of genes to powerfully drive smooth muscle cell into differentiation. We have previously demonstrated that ERα can repress the Myocardin activation for specific gene of smooth muscle cells, but also inhibit Myocardin expression. On this basis, this study will further determine that estrogen and ERα can inhibit the differentiation and promote proliferation and the related mechanisms by a variety of cell and molecular biology techniques and methods. At last, the novel molecular mechanisms of estrogen and ERα triggering uterine leiomyoma will be clarified. Important theoretical basis for the prevention and treatment of uterine fibroids and drug discovery or gene therapy will be provided by this study.

成功建立了SD大鼠子宫肌瘤模型，肉眼观和HE染色显示SD大鼠子宫肌瘤模型。免疫组化、RT-PCR、 western bloting结果显示Myocardin和SM22α的表达量在正常的子宫平滑肌组织中比子宫肌瘤组织中含量高。但是ERα、平滑肌增值标志基因PCNA的表达在子宫肌瘤组织中比在正常的子宫平滑肌组织中表达量要高。荧光素酶活性检测技术结果在原代细胞中显示myocardin驱动SM22 Luciferease的活性，而ERα抑制myocardin驱动的SM22 Luciferease的活性，并且ERα的抑制作用随着ERα的浓度改变而变化。 CO-IP结果表明ERα和myocardin有相互作用，免疫荧光表明ERα抑制myocardin的表达。ERα抑制myocardin的表达。1. Myocardin通过与CArG-box结合激活下游分化基因SM22α的转录和蛋白表达。2. ERα通过抑制myocardin对SM22α转录激活和表达，从而抑制子宫平滑肌细胞的分化。3. ERα和myocardin存在直接蛋白-蛋白相互作用；ERα和Myocardin蛋白复合物可能影响Myocardin-SRF与CArG-box结合，进而抑制其驱动的子宫平滑肌细胞的分化作用；并且，其抑制作用与ERα的浓度呈正相关。