基于网络药理学探索生化汤治疗小腹痛的药理机制
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摘要
《傅青主女科》中所记载的生化汤为产后常用方,广泛应用于产后及妇科诸症,但其治疗小腹痛的作用机制尚不明确。该文应用网络药理学,探索生化汤治疗小腹疼痛的作用机制,为临床更好的使用生化汤提供数据支持。在SymMap中分别检索小腹痛和生化汤药物的靶标,运用String和Cytoscape进行富集分析,构建症-药-靶标生物网络。结果显示,生化汤中含有靶标400个,其中11个与小腹痛的疾病基因重合;经String分析,得到基因间互作关系18个;经模块化处理后,得到含有6个基因的1个模块;经String富集分析,得到biological process富集结果 170条、molecular function富集结果 2条、KEGG pathways富集结果 30条。生化汤可能通过神经-内分泌-免疫、代谢等多方面参与小腹痛的治疗过程,其机制为通过加快子宫内组织细胞的修复增长,改善微循环,促进子宫内膜细胞更新及炎症消退,加速子宫复旧,同时调节自身免疫力,应用信号通路在部分天然免疫细胞抗感染过程中的功能和调控作用,补益正气,引邪外达,而达到治疗小腹痛的效果。
The Shenghua Decoction recorded in Fu Qing Zhu's Gynaecology,is a commonly used postpartum prescription,widely used in treating postpartum and gynecological diseases. However,its mechanism of action in treating lower abdominal pain remains unclear. In this paper,network pharmacology was used to explore the mechanism of Shenghua Decoction in the treatment of lower abdomen pain,so as to provide data support for better clinical application of Shenghua Decoction. The drug targets of lower abdominal pain and Shenghua Decoction were retrieved in SymMap. String and Cytoscape were adopted for enrichment analysis to construct the disease-drug-target biological network. Relevant gene search results showed that there were 400 targets in Shenghua Decoction,11 of which coincided with the disease genes of lower abdomen pain. In String analysis,18 gene interactions were obtained. Gene modularizationbased analysis results indicated that one module containing six genes was obtained after modularization processing. Furthermore,there were 170 enrichment results of biological process,2 enrichment results of molecular function and 30 enrichment results of KEGG pathways in String enrichment analysis. Shenghua Decoction may play a role in treating lower abdomen pain through neuro-endocrine-immune,metabolism and other means. Its mechanism may be achieved by accelerating the repair and growth of endometrial tissue cells,improving microcirculation,promoting endometrial cell renewal and inflammation subsidence,and accelerating uterine involution; at the same time,it can regulate the autoimmunity,regulate and control the function of some natural immune cells in the process of antiinfection by using signaling pathway,supplement the vital energy,and induce elimination of pathogens from the body,thereby achieving the effect of treating lower abdomen pain.
The Shenghua Decoction recorded in Fu Qing Zhu's Gynaecology,is a commonly used postpartum prescription,widely used in treating postpartum and gynecological diseases. However,its mechanism of action in treating lower abdominal pain remains unclear. In this paper,network pharmacology was used to explore the mechanism of Shenghua Decoction in the treatment of lower abdomen pain,so as to provide data support for better clinical application of Shenghua Decoction. The drug targets of lower abdominal pain and Shenghua Decoction were retrieved in SymMap. String and Cytoscape were adopted for enrichment analysis to construct the disease-drug-target biological network. Relevant gene search results showed that there were 400 targets in Shenghua Decoction,11 of which coincided with the disease genes of lower abdomen pain. In String analysis,18 gene interactions were obtained. Gene modularizationbased analysis results indicated that one module containing six genes was obtained after modularization processing. Furthermore,there were 170 enrichment results of biological process,2 enrichment results of molecular function and 30 enrichment results of KEGG pathways in String enrichment analysis. Shenghua Decoction may play a role in treating lower abdomen pain through neuro-endocrine-immune,metabolism and other means. Its mechanism may be achieved by accelerating the repair and growth of endometrial tissue cells,improving microcirculation,promoting endometrial cell renewal and inflammation subsidence,and accelerating uterine involution; at the same time,it can regulate the autoimmunity,regulate and control the function of some natural immune cells in the process of antiinfection by using signaling pathway,supplement the vital energy,and induce elimination of pathogens from the body,thereby achieving the effect of treating lower abdomen pain.
引文
[1]刘影,张伟娟,任亚娟,等.生化汤的临床应用及实验药理[J].河南中医,2013,33(4):603.
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[5]洪敏,余黎,马骋,等.生化汤提取物对离体及产后子宫活动的影响[J].南京中医药大学学报,2003,19(5):154.
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[10]李波,雷珊珊,李贺,等.基于网络药理学的济脉通片降压机制研究[J].中国现代应用药学,2019,36(1):49.
[11]赵美荣.生化汤加味治疗血瘀型产后腹痛的临床观察[D].哈尔滨:黑龙江中医药大学,2012.
[12]谢黎.产后痛证的中西医病因分析[J].浙江中医药大学学报,2009,33(2):153.
[13]郝赫.JAK-STAT信号通道在动脉粥样硬化中的意义[J].吉林医学,2013,34(1):123.
[14]殷震惠,杨华.VEGF、JAK2/STAT3信号通路与妇科疾病的关系[J].国际妇产科学杂志,2016,43(6):708.
[15]李妹娟,王和生,王通渤,等.制何首乌中大黄素对Apo E-/-小鼠动脉粥样硬化模型中JAK2/STAT3通路的影响[J].中国实验方剂学杂志,2018,24(18):101.
[16]麻莉,成娅,任萍.早产孕妇绒毛膜促性腺激素及白细胞介素6水平的变化[J].中华妇产科杂志,2001(9):44.
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[20]石岳坚,郑翠苹,蔡小平,等. Th1/Th2细胞因子谱检测在血液肿瘤患者化疗后中性粒细胞缺乏伴感染时的应用[J].中国医师杂志,2016,18(5):737.
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[22] van der Horst A,Burgering B M. Stressing the role of Fox O proteins in lifespan and disease[J]. Nat Rev Mol Cell Biol,2007,8(6):440.
[23] Turner M D,Nedjai B,Hurst T,et al. Cytokines and chemokines:at the crossroads of cell signalling and inflammatory disease[J]. Biochim Biophys Acta,2014,1843(11):2563.
[24]魏恒,王诗卓.Wnt/JNK通路中效应因子在妇科肿瘤中的作用[J].国际妇产科学杂志,2012,39(1):45.
[25]李玉席,李俊宏,周大旺.Hippo信号通路与肝脏稳态调控及疾病发生[J].遗传,2017,39(7):607.
[26]余淑娟,耿晶,陈兰芬.Hippo信号通路调控免疫细胞的功能[J].遗传,2017,39(7):650.
[2]李喜香,罗燕梅,冯守文,等.新生化汤口服液药效学研究[J].中成药,2000,22(10):737.
[3]周辛,白世泽,李新生,等.血停灵冲剂的药效学研究[J].中国中医药科技,1997,4(5):271.
[4]洪敏,余黎,马骋,等.生化汤提取物对孕末期家兔子宫体及子宫颈肌电活动的影响[J].中国中药杂志,2003,28(12):1162.
[5]洪敏,余黎,马骋,等.生化汤提取物对离体及产后子宫活动的影响[J].南京中医药大学学报,2003,19(5):154.
[6]任青华,王丽.生化汤、四物汤加减补阳还五汤体外抗血栓的研究[J].中成药,1993(1):44.
[7] Ozaki Y,Ma J P. Inhibitory effects of tetramethylpyrazine and ferulic acid on spontaneous movement of ratuterus in situ[J].Chem Pharm Bull(Tokyo),1990,38(6):1620.
[8]王雁梅,史恒军,王保秀,等.生化汤药理学研究进展[J].中国药房,2005(6):69.
[9] Hopkins A L. Network pharmacology[J].Nat Biotechnol,2007,25(10):1110.
[10]李波,雷珊珊,李贺,等.基于网络药理学的济脉通片降压机制研究[J].中国现代应用药学,2019,36(1):49.
[11]赵美荣.生化汤加味治疗血瘀型产后腹痛的临床观察[D].哈尔滨:黑龙江中医药大学,2012.
[12]谢黎.产后痛证的中西医病因分析[J].浙江中医药大学学报,2009,33(2):153.
[13]郝赫.JAK-STAT信号通道在动脉粥样硬化中的意义[J].吉林医学,2013,34(1):123.
[14]殷震惠,杨华.VEGF、JAK2/STAT3信号通路与妇科疾病的关系[J].国际妇产科学杂志,2016,43(6):708.
[15]李妹娟,王和生,王通渤,等.制何首乌中大黄素对Apo E-/-小鼠动脉粥样硬化模型中JAK2/STAT3通路的影响[J].中国实验方剂学杂志,2018,24(18):101.
[16]麻莉,成娅,任萍.早产孕妇绒毛膜促性腺激素及白细胞介素6水平的变化[J].中华妇产科杂志,2001(9):44.
[17] Macpherson A J,Mc Coy K D,Johansen F E,et al. The immune geography of Ig A induction and function[J]. Mucosal Immunol,2008,1(1):11
[18] Wang F,Li H,Yang Z,et al. Expression of interleukin-10 in patients with adenomyosis[J]. Fertil Steril,2009,91(5):1681.
[19]周义忠,颜如,刘梅,等.血IL-10、IL-5、IL-2、IFN-γ水平在反复腹痛患儿及其家庭成中的比较[J].昆明医学院学报,2012,33(6):66.
[20]石岳坚,郑翠苹,蔡小平,等. Th1/Th2细胞因子谱检测在血液肿瘤患者化疗后中性粒细胞缺乏伴感染时的应用[J].中国医师杂志,2016,18(5):737.
[21] Engelman J A,Luo J,Cantley L C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism[J].Nat Rev Genet,2006,7(8):606.
[22] van der Horst A,Burgering B M. Stressing the role of Fox O proteins in lifespan and disease[J]. Nat Rev Mol Cell Biol,2007,8(6):440.
[23] Turner M D,Nedjai B,Hurst T,et al. Cytokines and chemokines:at the crossroads of cell signalling and inflammatory disease[J]. Biochim Biophys Acta,2014,1843(11):2563.
[24]魏恒,王诗卓.Wnt/JNK通路中效应因子在妇科肿瘤中的作用[J].国际妇产科学杂志,2012,39(1):45.
[25]李玉席,李俊宏,周大旺.Hippo信号通路与肝脏稳态调控及疾病发生[J].遗传,2017,39(7):607.
[26]余淑娟,耿晶,陈兰芬.Hippo信号通路调控免疫细胞的功能[J].遗传,2017,39(7):650.