| This paper includes three parts:literature review,clinical research and network pharmacology research.Part 1:literature reviewHypertension is a common chronic disease,which is closely related to the morbidity and mortality of cardiovascular and cerebrovascular diseases.It seriously threatens the life and health of citizens and causes heavy economic burden to families and the country.Primary hypertension accounts for 95%of the prevalence of hypertension,which is affected by both genetic factors and acquired environmental factors.Dietary habits,obesity and overweight,insulin resistance,insomnia,sympathetic activation,renin-angiotensin-aldosterone system and other important factors are the pathogenesis of hypertension.The treatment of hypertension in western medicine includes non-drug treatment and drug treatment.Non-drug treatment mainly includes paying attention to diet,strengthening exercise,regulating emotion and adjusting sleep.In addition,traditional Chinese medicine has its advantages and unique features in the treatment of the disease.Hypertension belongs to the category of "headache" and "vertigo" in traditional Chinese medicine.There are descriptions of vertigo and headache in "neijing",and vertigo is called"head wind" and "brain wind".The pathogenesis can be induced by institutional endowment,internal injury of emotion,loss of diet,and loss of work and rest.The basic pathogenesis is closely related to phlegm drinking,blood stasis,and liver wind.The treatment of TCM includes both drug therapy and non-drug therapy.Non-drug therapies include acupuncture and moxibustion therapy,taijiquan,baduanjin and other traditional sports therapy.According to the syndrome differentiation,non-drug therapy can be divided into the method of nourishing water and culm,the method of clearing liver and relieving fire,the method of strengthening spleen and dampness,the method of activating blood and removing blood stasis,and the method of strengthening kidney and liver and strengthening spleen.Previous basic studies have confirmed the efficacy of ’yishenpingganjianpi’ formula in lowering blood pressure,improving myocardial fibrosis and protecting hypertensive kidney damage.This paper mainly discusses the clinical efficacy of yishenpingganjianpi formula in treating hypertension.Part 2:clinical researchObjective:To observe the clinical effect of traditional Chinese medicine(TCM)-’Yishenpingganjianpi’ formula(Sang-qi granule)on primary hypertension by single arm and before and after controlled clinical trial.Methods:A total of 168 patientswith grade 1 and grade 2 hypertension who met the inclusion criteria were enrolled in China-Japan friendship hospital from September 2007 to January 2019(89 enrolled subjects from September 2007 to January 2015 and 79 enrolled subjects from September 2016 to January 2019).Every patient was treated with Sang-qi granule,1 pack(10 g)each time,half an hour after breakfast and dinner every day.The intervention time was 8 weeks,followed up once every 2 weeks,and the hematological indexes,24-hour dynamic blood pressure monitoring,syndrome scale and sleep scale were measured at 2 time points of day 0 and day 56(week 8).The blood pressure in the clinic and the symptom scale were measured every 2 weeks,and the changes of the above indexes were observed.All the data obtained were statistically processed using SAS 9.4 and SPSS 20.0 of Windows version.Results:(1)The systolic pressure,diastolic blood pressure after treatment was significantly different from before treatment(P<0.01).(2)The systolic blood pressure and diastolic blood pressure at week 2,week 4,week 6 and week 8 were significantly different from the baseline before treatment(P<0.01).(3)The symptom score after treatment was significantly different from that before treatment(P<0.01).The symptom scores at week 2,week 4,week 6 and week 8 were significantly different from the baseline before treatment(P<0.01).(5)There was a statistical difference in triglycerides after treatment compared with before treatment(P<0.05).(6)There were statistically significant differences in HDL between before and after treatment(P<0.01).(7)Syndrome types were divided into groups,and compared among groups,and the differences in symptom scores between groups before and after treatment were statistically significant(P<0.05).(9)The nocturnal systolic blood pressure after treatment was significantly different from that before treatment(P<0.05).(10)The difference of mean blood pressure between day and night after treatment was statistically different from that before treatment(P<0.05).(11)The diastolic blood pressure night and day minimum ratio after treatment was significantly different from that before treatment(P<0.05).(12)The decrease rate of systolic blood pressure after treatment was statistically different from that before treatment(P<0.05).(13)The total score of PSQI after treatment was significantly different from that before treatment(P<0.01).(14)The total sleep time score after treatment was statistically different from that before treatment(P<0.05).(15)The sleep efficiency score after treatment was statistically different from that before treatment(P<0.05).(16)The score of sleep disorder after treatment was statistically different from that before treatment(P<0.05).Conclusion:(1)Sang-qi granule has significant antihypertensive effect,which can significantly reduce the systolic and diastolic blood pressure.The antihypertensive effect is most obvious when used for 2 weeks,which can improve the circadian rhythm of blood pressure.(2)Sang-qi granule can significantly improve hypertension-related symptoms,among which the most obvious symptoms are constipation,facial red scorching,headache,dizziness,and the overall symptoms of patients with hyperphremia are improved best,followed by Yin deficiency and Yang hyperactivity,Yin and Yang deficiency,and excessive accumulation of phlegm and dampness.(3)Sang-qi granule has significantly improved the sleep.It can prolong the total time of sleep,improve sleep efficiency,improve sleep disorders.(4)Sang-qi granule has the function of reducing triglycerides and increasing HDL.Part 3:network pharmacology research.Objective:To predict the target sites of active components of yishenpinggan jianpi formula(Sang-qi granule)through network pharmacology,map the relevant targets of hypertension(EH),topologically identify the key points of interaction for enrichment analysis,and comprehensively explore the pharmacological mechanism of yishenpingganjianpi formula.Methods:Firstly,the main active components of yishenpingga jianpi formula were screened out from the pharmacological database and analysis platform TCMSP based on the pharmacokinetic characteristics(ADME),and compared with the medicinal chemical components in TCM@taiwan.Meanwhile,the molecular structure of yishenpingganjianpi formula was confirmed using the organic small molecule bioactivity database(PubChem).Then by using the Pharmmapper server,the "Reverse pharmacophore matching method"was used to obtain virtual screening protein results,and then used UniProt database to correct all proteins into their Official Gene Symbol.Through human Mendel database known EH therapeutic targets(OMIM)mining,combined forecast target import String database construction of kidney flat liver spleen and treatment target EH interaction network diagram,with the aid of Cytoscape software according to the relevant node topology of the interaction of key parameters,and finally by DAVID database analysis of metabolic pathways of key nodes.Results:10 active ingredients of yishenpingganjianpi formula were selected,and 70 related targets were predicted according to the target prediction technology.Through text mining,346 EH related specific targets were retrieved,and 58 duplicated genes were obtained.After text mining to retrieve the relevant clear targets 346,EH,get duplicated genes 58,according to the String network database construction of protein interaction network,after Cytoscape topology,select the key nodes of 33,extract the key of the core node 355 for interaction relations,enrichment analysis showed that the enrichment of eight targets involved in pathways have(RAS,PI3K-Akt)signal transduction pathway(28.9%),The pathways involved in 7 targets were enriched with actin cytoskeleton regulation and mitogen-activated protein kinase(MAPK),and the TNF signaling pathway involved in 5 targets.Conclusion:The network pharmacological study shows that yishenpingganjianpi formula may be involved in the regulation of several major signal pathways through direct or indirect targets,so as to play a role in the treatment of hypertension,and provide a scientific basis for the explanation of the material basis and mechanism of its antihypertensive effect. |
PDF Full Text Request