Clinical Study And Therapeutic Mechanism Of Yishen Huoxue Decoction In The Treatment Of Oligoasthenospermia

Research backgroundMale infertility means that the couple has lived together for more than one year,has a normal sexual life,has not used or accepted any contraceptive measures,and the male factor causes female infertility.Among couples who cannot conceive,men account for about half of the proportion.Factors affecting the prognosis of male infertility include the duration of infertility,the classification of infertility(primary or secondary),the results of semen analysis,the age and fertility status of the female partner,etc.The pathophysiological mechanisms of male infertility are complex and diverse,and there is currently no specific conclusion.In recent years,studies have found that excessive reactive oxygen species(ROS)produced during oxidative stress are an important cause.Excessive ROS can cause damage to sperm membrane,mitochondria,DNA,and motility,and can also cause sperm apoptosis.sperm apoptosis occurs in male infertility patients as the fragmentation of germ cell DNA causes programmed cell death.Sperm DNA fragmentation index(DFI)is an important indicator of sperm integrity.So,taking the oxidative stress response as a research entry point,observing the changes in the DFI index,and using bioinformatics methods to study the mechanism of sperm damage in male infertility can provide new ideas and methods for the treatment of male infertility.Male infertility is a category such as "no children","infertility","unsuccessful"in traditional Chinese medicine.Professor Zhang Yaqiang has rich experience in the treatment of male infertility,and the treatment of male infertility with the method of Yishen Huoxue has achieved good results.This study is divided into three parts:(1)Using data mining methods to summarize Professor Zhang’s experience in treating male infertility,and condense Yishen Huoxue Decoction;(2)A randomized controlled method was used to observe the clinical efficacy of Yishen Huoxue Decoction in the treatment of this disease;(3)Based on bioinformatics technology and network pharmacology,explore the curative effect mechanism of Yishen Huoxue Decoction.Part Ⅰ Analysis of professor Zhang’s medication rules for the treatment of male infertilityObjectThrough data mining,we went to understand the prescription characteristics of Zhang Yaqiang to treat male infertility find prescription association rules and summarize diagnosis and treatment experience of Zhang Yaqiang to treat male infertility.MethodsWe use SPSS analysis software to describe Zhang Yaqiang’s prescription for male infertility treatment,including the use of medicinal taste,an average of medication descriptions,etc.Take the Apriori algorithm to conduct mining of prescription drug data for Professor Zhang Yaqiang to treat male infertility and find the common association rules.To summarize Zhang Yaqiang’s law of using drugs for treating male infertility,condense experience prescription.ResultsProfessor Zhang’s treatment of male infertility consists of an average of 18 drugs per prescription.All prescriptions involve 130 Chinese medicines,with 20 kinds of drugs with more than 18%frequency.The common drug combination is”indian bread-chinese magnoliavine fruit-barbary wolfberry fruit-chinese angelica","flatstem milkvetch seed-indian bread-leech-solomonseal rhizome-Sichuan lovage rhizome" and "indian bread-barbary wolfberry fruit-peach seed-chinese magnoliavine fruit-sichuan lovage rhizome";Based on the research results and clinical experience,Professor Zhang reviewed and agreed to the Yishen Huoxue Decoction:chinese magnoliavine fruit 10g、sichuan lovage rhizome 10g、barbary wolfberry fruit 20g、dodder seed 15g、solomonseal rhizome 10g、Chinese angelica 10g、peach seed6g、twotoothed achyranthes root 15g、leech 5g、prepared rehmannia root 10g、flatstem milkvetch seed 10g、palmleaf raspberry fruit 8g.ConclusionProfessor Zhang’s treatment of this disease is mainly based on "Yishen Huoxue".Through data mining,Professor Zhang reviewed and agreed to condense Yishen Huoxue Decoction as the representative prescription of the treatment.Part Ⅱ Evaluation of therapeutic effect of Yishen Huoxue Decoction in treating male infertilityObjectTo observe the clinical efficacy of Yishen Huoxue Decoction and the treatment of kidney deficiency blood stasis type of male infertility,analyzing its indicators such as sperm quality,DNA fragmentation rate and Chinese medicine symptoms,Provide evidence-based medicine evidence and scientific basis for clinical promotion of this party.MethodsFrom May 2018 to May 2019,100 male infertility patients with kidney deficiency and blood stasis were randomly divided into experimental group(n=50)and control group(n=50).The experimental group was treated with Yishen Huoxue Decoction,and the control group was treated with vitamin E capsules and tamoxifen tablets.After 12 weeks,compare the therapeutic effect,record each indicator before and after treatment,including Chinese medicine symptoms,sperm concentration,semen volume,forward sports sperm,normal form sperm,sperm debris DNA rate(DFI),superoxide dismutase(SOD),Malondialdehyde(MDA),vascular endothelial growth factor(VEGF)and seminal plasma zinc,fructose change,statistical two group conception rates,live yield.Results2 cases of experimental group were taken off,and 3 cases of control group were taken off.After 12 weeks of treatment,two groups of traditional Chinese medicine symptoms,sperm concentrations,semen volume,forward sports sperm,normal form sperm,DFI,SOD,MDA,VEGF,seminal plasma zinc,fructose and other indicators were more prominent,there was a significant difference(P<0.05),the experimental group was better than the control group;At the total effective rate,the experimental group was 93.75%,and the control group was 78.72%,which had a significant difference(P<0.05);The experimental group was compared with the conception rate of the control group(22.92%vs 19.15%),and the yield ratio(22.92%vs 17.02%)was not significantly different(P>0.05).Yishen Huoxue Decoction can improve sperm mass and DFI of male infertility patients and effectively improve the SOD,VEGF levels of male infertility patients,reduce the MDA content,improve seminal plasma zinc and fructose level and improve the symptoms of traditional Chinese medicine.ConclusionStudies have shown that Yishen Huoxue Decoction can improve the sperm quality of patients.Clinical studies have further verified the generalizability of Professor Zhang’s medication rules summarized through data mining.Part Ⅲ Analysis of the mechanism of Yishen Huoxue Decoction based on bioinformaticsObjectWith the help of bioinformatics,Using network pharmacology to deeply explore the potential targets and pathways of Yishen Huoxue Decoction in the treatment of male infertility,and exploring the possible mechanism of the effect of Yishen Huoxue Decoction,laying a foundation for in-depth research on the efficacy mechanism of this prescription.MethodsUsing Network Pharmacology to analyze the relationship between drug active ingredients,active ingredient targets and disease treatment targets to treat programs,effective ingredients,and disease treatment targets,predict potential pharmacological mechanisms of Yishen Huoxue Decoction.Further,by retrieving the gene expression integrated database(GEO),the gene expression chip data(microarry),analyzing the differentially expressed genes between spermatogenesis and sperm injury,and preliminarily explore the potential pathways and targets of Yishen Huoxue Decoction for male infertility.ResultsThere are 151 joint effects of Yishen Huoxue Decoction and male infertility.By drawing the relationship between "Yishen Huoxue Decoction-Active ComponentsTarget-Men Infertility",the topological map is obtained,and the interaction between"Effective ingredient" and "Disease Gene Target" are initially revealed.Taking the human protein group as the condition,it is obtained from the effectiveness of the male infertility disease.539 interactions between 151 related disease target gene protein products.The functional enrichment of utility target is further found by GO and KEGG genomic database analysis.Screening the human differential expression gene of male infertility,In all targets of Yishen Huoxue Decoction,25 targets are the up-regulating genes in male infertility gene expression spectrum;26 targets are a down-regulated gene in male infertility gene;Three targets differ in multiple biological processes associated with male infertility.ConclusionBioinformatics studies have suggested that Yishen Huoxue Decoction mainly interferes with the pathophysiological process of male infertility by affecting oxidative stress and other reactions.The results of enrichment analysis of the biological effects of the useful targets of the Yishen Huoxue Decoction show that the significant biological effects of these targets exist in biochemical processes such as antioxidant activity,mainly by affecting the AGE-RAGE signal pathway,regulating the AGE-RAGE clearance efficiency,and reducing local inflammation and oxidative stress levels are effective,the above research results have laid a solid foundation for in-depth and comprehensive disclosure of the therapeutic effect of Yishen Huoxue Decoction on the treatment of this disease.