基于RNA测序和iTRAQ标记定量蛋白组等系统生物学技术探讨蒙药乳腺-I号治疗乳腺增生病的作用机制

Of various breast diseases, hyperplasia of mammary glands accounts for 75%, and tends to younger age. It is one of the high risk factor for breast cancer which threats greatly to women's physical and mental health. The Mongolian Medicine, Ruxian-I, was effective to treat hyperplasia of mammary glands. Immunohistochemistry, western blotting, RT-PCR proteomics etc. were applied to investigate the mechanism of the treatment of Mongolian Medicine Ruxian-I on hyperplasia of mammary glands in rats, which indicated that Ruxian-I can improve the pathological state of breast tissue, regulate serum sex hormone levels, reduce the expression of estrogen and progesterone receptor in treating hyperplasia of mammary glands. However, the targets and molecular mechanism remains to be further elucidated. The emergence of systems biology provides a new thought for the mechanism evaluation of Chinese herbal compound prescription. In this work, we attempt to use systems biology approach such as the second generation RNA-Seq sequencing technology and iTRAQ quantitative proteomics to clarify the pharmacological mechanism of Mongolian Medicine Ruxian-I and analyze the drug target for hyperplasia of mammary glands, in order to explore the new way for the mechanism research of the prescription of Mongolian Medicine.

乳腺增生症占全部乳腺疾病的75％，且趋向低龄化，也是乳腺癌的高危风险因子之一，对广大妇女身心健康形成的巨大威胁。蒙药乳腺-I号治疗乳腺增生疗效确切。我们利用免疫组织化学、Western blotting、RT-PCR蛋白质组学等对蒙药乳腺-Ⅰ号对大鼠乳腺增生的治疗机制进行了探讨，表明蒙药乳腺-Ⅰ号可通过改善乳腺组织病理状态，调节血清性激素水平，降低乳腺组织雌、孕激素受体表达等作用治疗乳腺增生症。但是作用靶点和分子机制还有待于深入阐明。系统生物学的的出现为中药复方作用机制评价提供了全新的思路，本课题拟采用RNA-Seq二代测序技术和iTRAQ定量蛋白组等系统生物学方法，阐明蒙药复方乳腺-I号的药理作用机制，解析复方蒙药乳腺-Ⅰ号对于乳腺增生症的药物作用靶点，为蒙药复方的机制研究探索新的途径。

乳腺增生症占全部乳腺疾病的75％，且趋向低龄化，也是乳腺癌的高危风险因子之一，对广大妇女身心健康形成的巨大威胁。蒙药乳腺-I号治疗乳腺增生疗效确切。我们利用免疫组织化学、Western blotting、RT-PCR蛋白质组学等对蒙药乳腺-Ⅰ号对大鼠乳腺增生的治疗机制进行了探讨，表明蒙药乳腺-Ⅰ号可通过改善乳腺组织病理状态，调节血清性激素水平，降低乳腺组织雌、孕激素受体表达等作用治疗乳腺增生症。但是作用靶点和分子机制还有待于深入阐明。系统生物学的的出现为中药复方作用机制评价提供了全新的思路。.该课题按照计划执行相关研究，首先我们再次复制大鼠乳腺增生证模型，采用RNA-Seq二代测序技术和iTRAQ定量蛋白组等系统生物学方法，探讨蒙药乳腺-I号治疗乳腺增生证机制，蒙药乳腺-I号是由30味药组成，成分极其复杂，研究发现蒙药乳腺-I号治疗大鼠乳腺增生证作用机制复杂，选择我们关切的三个方面进行了验证，得到如下结论：..抗凋亡蛋白TCTP与大鼠HMG的发生发展紧密相关，并可能作为蒙药乳腺-Ⅰ号治疗HMG的靶标蛋白； 蒙药乳腺-Ⅰ号治疗乳腺增生症的机制可能是通过TCTP蛋白调节的细胞凋亡通路。..蒙药乳腺-I号降低TNF-α水平的同时抑制MAPK和NF-κB信号通路中关键蛋白p-ERK、p-JNK、p-P38、p-NF-κB及p-IκBα蛋白的表达，使乳腺增生程度减轻。..蒙药乳腺-I号下调了HMG大鼠乳腺组织的CRYAB蛋白的上调水平，增强了ERS蛋白GRP78与CHOP下调水平，诱导了细胞凋亡相关蛋白的表达水平。.