基于定量蛋白质组学探讨西黄丸抗乳腺增生的作用机制  

Exploring mechanism of action of Xihuang pills against hyperplasia of mammary glands based on quantitative proteomics

作　　者：陶蕊 王婧瑞 王俊亮 马学莉 孙娟霞 高广淼 范琪瑞 韩涛[1,2] TAO Rui;WANG Jing-rui;WANG Jun-liang;MA Xue-li;SUN Juan-xia;GAO Guang-miao;FAN Qi-rui;HAN Tao(Dept of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;Gansu Provincial Key Laboratory of Pharmacology and Toxicology of Chinese Medicines,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学中药学教研室,甘肃兰州730000 [2]甘肃省中药药理与毒理学重点实验室,甘肃兰州730000

出　　处：《中国药理学通报》2024年第9期1641-1648,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金地区项目(No 82160853);甘肃省科技计划项目(No 21JR1RA264)。

摘　　要：目的基于定量蛋白质组学技术明确西黄丸抗乳腺增生(hyperplasia of mammary glands,HMG)中乳腺组织的差异蛋白并验证,探讨其作用机制。方法将SD大鼠随机分为空白组、模型组和西黄丸组,每组10只。除空白组外,肌注雌孕激素建立HMG大鼠模型,为期30 d。给药西黄丸14 d后,观察各组大鼠表观形态变化,HE染色观察乳腺组织病理改变,定量蛋白质组学技术筛选各组差异表达蛋白(differentially expressed proteins,DEPs),并进行生物信息学分析和Western blot验证。结果与模型组比较,西黄丸组表观病理形态明显改善,大鼠乳头高度直径明显降低(P<0.01),组织病理程度明显缓解。定量蛋白质组学鉴定出乳腺组织4299个DEPs,对西黄丸组与空白组相对模型组变化一致的14个DEPs进行生物信息学分析,发现与肌肉系统过程的调节、肌肉收缩调节、DNA复制和DNA复制启动前过程有关。Western blot结果表明,与模型组比较,西黄丸组大鼠乳腺组织ACLY与ALDOC蛋白表达水平明显降低,BIN1蛋白表达水平明显增加(P<0.01)。结论西黄丸可能通过调控BIN1、ACLY及ALDOC蛋白水平,调控DNA复制、DNA复制启动前和肌肉系统过程的调节、肌肉收缩调节等途径发挥抗HMG作用。Aim To clarify the differential proteins of mammary tissues in Xihuang pills(XHP)against hyperplasia of mammary glands(HMG)based on quantitative proteomics technology and validate them,and to explore the mechanism of action.Methods SD rats were randomly divided into blank group,model group and XHP group,with 10 rats in each group.Except for the blank group,estrogen and progesterone were injected intramuscularly to establish a rat model of mammary hyperplasia for 30 d.After XHP was administered for 14 d,the rats in each group were observed to have morphological changes in the apparent morphology of the mammary tissues,and pathological changes in the mammary tissues were stained with hematoxylin-eosin staining(HE),and the differentially expressed proteins(DEPs)in the groups were screened by quantitative proteomics technology and subjected to bioinformatics analysis,and Western blot to verify the key DEPs.Results Compared with the model group,the apparent pathological morphology of the XHP group was significantly improved,the diameter of the nipple height of the rats was significantly reduced(P<0.01),and the degree of histopathology was significantly alleviated.Quantitative proteomics identified 4,299 DEPs in mammary tissue,and bioinformatics analysis of 14 DEPs with consistent changes between the XHP group and the blank group relative to the model group revealed that they were related to the regulation of muscular systemic processes,regulation of muscle contraction,DNA replication,and pre-initiation of DNA replication.Western blot results showed that,compared with the model group,rat mammary tissue of the XHP group showed significantly lower levels of ACLY and ALDOC protein expression levels were significantly reduced and BIN1 protein expression levels were significantly increased(P<0.01).Conclusions XHP may exert its anti-mammary hyperplasia effect through the regulation of BIN1,ACLY and ALDOC protein levels,the regulation of DNA replication,the regulation of pre-initiation of DNA replication and muscular systemic

关 键 词：西黄丸 蛋白质组学 乳腺增生 BIN1蛋白 ACLY蛋白 ALDOC蛋白 

分 类 号：R-332[医药卫生] R285.5R323.23R341R655.8R977.6