基于网络药理学和生物信息学探索金匮肾气丸治疗近视的分子机制
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摘要
目的:探讨金匮肾气丸治疗近视的分子机制。方法:运用系统药理学方法筛选金匮肾气丸活性成分及活性成分靶点预测,通过生物信息学方法,确定金匮肾气丸治疗近视的作用靶点,并进行富集分析预测可能的作用信号通路,探讨金匮肾气丸治疗近视的分子作用机制。结果:完成了金匮肾气丸的主要活性成分筛选和靶点预测,筛选出近视的治疗靶点,完成信号通路的富集分析;金匮肾气丸能够调控甲状腺信号通路、雌激素信号通路等信号通路,影响视网膜视锥细胞的分化、视蛋白的合成以及巩膜的重塑等过程,抑制近视的发生发展。结论:金匮肾气丸主要是通过影响视锥细胞细胞分化、视蛋白的合成以及巩膜重塑等过程治疗近视。
Objective: To investigate the molecular mechanism of Jingui Shenqi Pills in the treatment of myopia. Methods: The pharmacokinetic method was used to screen the active ingredients and active ingredients of Jingui Shenqi Pills. The bioinformatics method was used to determine the therapeutic target of Jingui Shenqi Pills in the treatment of myopia,and the enrichment analysis was used to predict the possible effects and explore the molecular mechanism of Jingui Shenqi Pills in the treatment of myopia. Results: The main active ingredients screening and target prediction of Jingui Shenqi Pills were completed,and the therapeutic target of myopia was screened and the enrichment analysis of signal pathway was completed. Jinguui Shenqi Pills could regulate thyroid signaling pathway,estrogen signal pathway and so on,the impact of retinal cone cell differentiation and the synthesis of protein and sclera remodeling process,and inhibit the occurrence and development of myopia. Conclusion: Jingui Shenqi Pills mainly treat myopia by affecting the differentiation of cone cells,the synthesis of opsin and sclera remodeling.
Objective: To investigate the molecular mechanism of Jingui Shenqi Pills in the treatment of myopia. Methods: The pharmacokinetic method was used to screen the active ingredients and active ingredients of Jingui Shenqi Pills. The bioinformatics method was used to determine the therapeutic target of Jingui Shenqi Pills in the treatment of myopia,and the enrichment analysis was used to predict the possible effects and explore the molecular mechanism of Jingui Shenqi Pills in the treatment of myopia. Results: The main active ingredients screening and target prediction of Jingui Shenqi Pills were completed,and the therapeutic target of myopia was screened and the enrichment analysis of signal pathway was completed. Jinguui Shenqi Pills could regulate thyroid signaling pathway,estrogen signal pathway and so on,the impact of retinal cone cell differentiation and the synthesis of protein and sclera remodeling process,and inhibit the occurrence and development of myopia. Conclusion: Jingui Shenqi Pills mainly treat myopia by affecting the differentiation of cone cells,the synthesis of opsin and sclera remodeling.
引文
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[2]丁美华,吴建峰,叶翔,等.透镜诱导型近视肾阳虚豚鼠巩膜MMP-2及其抑制剂TIMP-2的表达[J].眼科新进展,2015,35(11):1005-1010.
[3]Martin A,Ochagavia M E,Rabasa L C,et al.BisoGenet:a new tool for gene network building,visualization and analysis[J].BMC Bioinformatics,2010,11(1):91.
[4]Nickla D L,Damyanova P,Lytle G.Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor L-NAME[J].Exp Eye Res,2009,88(6):1092-1099.
[5]朱玉广,刘双珍,吴小影,等.视网膜内源性NO在形觉剥夺性近视眼中的作用[J].湖南医科大学学报,2003,28(6):631-634.
[6]T F,Y K,J F,et al.The effect of nitric oxide synthase inhibitor on form-deprivation myopia[J].Current eye research,1997,16(10):992-996.
[7]J FISCHER A,LP SELTNER R,Stell W.Opiate and N-methyl-D-aspartate receptors in form-deprivation myopia[M].Visual Neuroscience,1998,15:1089-1096.
[8]Wen D,Liu S,Mao J,et al.MK801 controls form-deprivation myopia by nitric oxide-cyclic GMP signaling pathway in guinea pig[M].Journal of Central South University(Medical Science),2012,37(7):737-742.
[9]Raman M,Chen W,Cobb M H.Differential regulation and properties of MAPKs[J].Oncogene,2007,26(22):3100-3112.
[10]段宏莉.羟基脲制作SD大鼠肾阳虚证模型的规范化研究[D].广州:广州中医药大学,2005.
[11]肖静,王毅兴,高建东,等.肾阳虚证的研究进展[J].上海中医药大学学报,2008(2):73-77.
[12]林森,冯松杰.肾阳虚证历史回顾及现代研究[J].河北中医,2011(3):463-465.
[13]Forrest D,Erway LC,Ng L,et al.Thyroid hormone receptorβis essential for development of auditory function[J].Nature genetics,1996,13(3):354-357.
[14]Roberts M R,Srinivas M,Forrest D,et al.Making the gradient:Thyroid hormone regulates cone opsin expression in the developing mouse retina[J].Proc Natl Acad Sci U S A,2006,103(16):6218-6223.
[15]Glaschke A,Schlaudraff J,Del Turco D,et al.Thyroid Hormone Controls Cone Opsin Expression in the Retina of Adult Rodents[M].2011.
[16]A K,M E L,A G P,et al.Transfection of v-ras H DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity[J].Science(New York,N.Y.),1985,228(4700).
[17]L Fitzpatrick J,L Mize A,B Wade C,et al.Estrogen-mediated neuroprotection against beta-amyloid toxicity requires expression of estrogen receptor alpha or beta and activation of the MAPK pathway[J].Journal of Neurochemistry,2002,82(3):674-682.
[18]Burns K,Li Y,Arao Y,et al.Selective Mutations in Estrogen Receptor D-domain Alters Nuclear Translocation and Non-estrogen Response Element Gene Regulatory Mechanisms[J].Journal of Biological Chermztry,2011,286(14):12640-12649.
[19]Simoncini T,Hafezi-Moghadam A,Brazil D P,et al.Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase[J].2000,407(6803):538-541.
[20]曾丽明.FDM豚鼠RPE-脉络膜RA信号通路的研究[D].天津:天津医科大学,2011.
[21]Ye M,Hu D,Tu L,et al.Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells[J].Investigative Ophthalmology Visual Science,2008,49(2):497-504.
[22]杨琴.针灸及中药熏眼热疗联合使用治疗青少年近视的疗效观察[J].中国民康医学,2014(6):96-97.