Objective : Based on the fourth scientific research paradigm which combines theoretical exploration,data mining,network pharmacology and clinical research,to comprehensively explore old TCM doctor Jia Yuejin ’ s clinical treatment of insomnia disorder,the rules of medication and its core prescription(named Shugan An Mian Granules)The mechanism of action in the treatment of common syndromes of insomnia disorder.Methods:Firstly,used ancient and modern medical case cloud platform V2.2.3,the prescriptions of Jia Yuejin’s clinical treatment for insomnia disorder in the past five years to acquire the drug frequency,drug attribute statistics,drug association analysis,cluster analysis and complex network analysis to obtain core prescriptions(Shugan Anmian granules),common syndrome types(type of liver-stagnation transforming fire)and medication rules that can reflect his clinical thinking.Then utilized CNKI,TCMSP,Swiss Target Prediction,Swiss ADME and GEO,Gene Cards,OMMD,TTD,Uniprot and other databases to obtain the targets of the active ingredients of each drug of Shugan Anmian Granules and the disease targets of insomnia disorder and took the intersection,used Cytoscape V3.8.0 and The plug-in MCODE,Bi NGO,Clue GO and STRING databases respectively to construct disease-drug-ingredient-target network and protein interaction network and screen out the key ingredients and key targets in the network respectively;conducted GO and KEGG pathway enrichment analysis to obtain the mechanism of Shugan Anmian granules was predicted.Finally,33 patients with type of liver-stagnation transforming fire were enrolled in the experiment according to the criteria of Inclusion and exclusion.Among them,Shugan Anmian granules was used as the treatment group for 17 patients,and Shumian Capsule was used as the control group for 16 patients.During the period,patients are prohibited from using other drugs or non-drug therapies with sedative and hypnotic effects.After the experiment,the patients’ treatment was judged based on the Pittsburgh sleep index scale score,the SPIEGEL sleep scale score,and the changes in serum neurotransmitter gamma-aminobutyric acid(GABA),5-hydroxytryptamine(5-HT),and dopamine(DA)concentrations The changes before and after to realize the clinical efficacy,safety judgment and mechanism verification of Shugan Anmian Granules in the type of liver-stagnation transforming fire insomnia disorder.Results:(1)Data mining included 224 cases,including 271 prescriptions,involving140 Chinese medicines;the properties of the medicine were mostly mild,warm,and slightly cold;the taste of the medicine was mainly sweet,pungent,and bitter;the medicine mainly belonged to: liver,spleen,heart,lung,stomach,kidney and other meridians;through drug association analysis,cluster analysis and complex network analysis,the core prescriptions of eleven drugs can be obtained: Poria,Atractylodes,Albizia,Bupleurum,Cyperus rotundus,White Peony,Dragon Bone,Angelica,Moutan bark,Gardenia,Imperata cylindrica roots are highly consistent with Shugan Anmian granules.(2)Network pharmacology has obtained 65 active ingredients of Shugan Anmian granules,490 related targets,142 intersection targets.The key ingredients include β-sitosterol and stigmasterol.The key target clusters are: cytokines And neurotransmitters,etc.;(3)GO functional enrichment analysis results mainly include: metabolic process,immune system process and signal process;KEGG pathway enrichment analysis results mainly include: neuroactive ligand-receptor interaction,serotonergic synapse,Dopaminergic synapses,etc.(4)Clinical research can conclude that the serum 5-HT and DA levels of patients in the Shugan Anmian granule treatment group were significantly reduced while GABA level was up.(P<0.05).Conclusion:It is concluded that Jia Yuejin’s treatment in type of liver-stagnation transforming fire insomnia disorder is mainly achieved through multi-component and multi-target regulation of 5-HT,DA and GABA neurotransmitters,thus reflecting the importance of the fourth scientific research paradigm to the scientific research of Chinese medicine certainly guiding significance. |