Mechanism And Clinical Efficacy Of Replenish Qi And Activate Blood And Dispel Stasis In The Treatment Of Ischemic Stroke Based On Data Mining And Network Pharmacology

Chapter 1 Mechanism of Ischemic Stroke with Qi Deficiency and Blood Stasis Based on Data Mining and Network PharmacologyObjective:Data mining was conducted on the clinical application of traditional Chinese medicine for treating Qi deficiency and blood stasis ischemic stroke in the past decade,and a new herbal formula was developed based on the mining results.The potential mechanism of the new formula for anti-ischemic stroke was determined through network pharmacology analysis.Finally,the therapeutic mechanism of the new formula based on the method of replenish Qi and activate blood and expel stasis was verified through basic experiments for treating ischemic stroke.Methods:Firstly,data mining was conducted on the clinical literature related to Qi deficiency and blood stasis ischemic stroke using the CNKI,Wanfang,and PubMed databases.Then,network pharmacology was employed to screen key candidate targets and signaling pathways for the potential effect of a new herbal formula based on the method of replenish Qi and activate blood and expel stasis for treating ischemic stroke.Finally,animal experiments were conducted to evaluate the therapeutic mechanism of the new herbal formula.2,3,5-triphenyltetrazolium chloride(TTC)staining and Longa score were used to assess infarct volume and neurological deficits,immunohistochemistry was employed to observe the changes in NeuN expression,and Western blot was used to detect the expression of relevant signaling pathway proteins.Results:Through data mining,commonly used drugs for treating qi deficiency and blood stasis type ischemic stroke were identified,including Huangqi,Chuanxiong,Sanleng,and Ezhu(HCSE).Network pharmacology analysis identified 23 active compounds in HCSE that mainly act on 327 target genes.Key target genes were MAPK3,MAPK1,HSP90AA1,STAT3,PIK3R1,PIK3CA,and Akt1.KEGG enrichment analysis showed significant enrichment of the PI3K/Akt and MAPK/ERK signaling pathways.Through TTC staining,Longa scoring,immunohistochemical observation,and western blot analysis,we found that HCSE can reduce infarct volume induced by MCAO in mice,resist neurological function deficit,and reduce neuronal death,mainly by activating the PI3K/Akt and MAPK/ERK signaling pathways.This confirms that the new prescription of the method of invigorating qi,activating blood circulation,and removing blood stasis has a significant protective effect against ischemic stroke injury by activating the PI3K/Akt and MAPK/ERK signaling pathways.Conclusion:This study employed data mining and network pharmacology analysis to discover a new herbal formula,HCSE,based on the method of replenish Qi and activate blood and expel stasis for treating ischemic stroke.Its therapeutic effect is achieved through regulating multiple target genes and pathways.Further experimental studies have shown that the anti-ischemic injury effect of HCSE is realized through the PI3K/Akt and MAPK/ERK signaling pathways,providing experimental evidence for the clinical application of HCSE in treating ischemic stroke.Chapter 2 Clinical Study of Formulation Based on the Method of Replenish Qi and Activate Blood and Expel Stasis in the Treatment of Mild Ischemic StrokeObjective:To observes the clinical efficacy of Formulation(HCSE)in treating minor ischemic stroke(MIS)based on the method of replenish Qi and activate blood and expel stasis.It also explores and analyzes the underlying mechanisms of HCSE’s therapeutic effects.Methods:A total of 76 patients diagnosed with MIS and treated at the Yangzhou Hospital of Traditional Chinese Medicine between December 2021 and December 2022 were selected.The final complete data of 68 patients who met the inclusion criteria of this study were divided into a control group(n=34)and an intervention group(n=34).Patients in the control group were given basic treatment for ischemic stroke,while HCSE was added to the basic treatment for patients in the intervention group.Both groups of patients were treated continuously for 14 days.Changes in the efficacy indicators such as the The National Institutes of Health Stroke Scale(HINSS),modified Rankin Scale(mRS),traditional Chinese medicine(TCM)syndrome scores,D-dimer,and coagulation function before and after 14 days of treatment,as well as the incidence of recurrence at 90 days,and ABCD2 score were compared between the two groups to explore effective methods for the prevention and treatment of MIS.Results:The baseline data of the two patient groups collected were basically consistent and there was no significant difference(P>0.05).The total prevalence of hypertension in the two groups was 51 cases,which was the highest among the basic diseases,accounting for 75%of the total number of two groups.Regarding the comparison of neurological function,prognosis,and TCM syndrome scores before and after treatment between the two patient groups,the NIHSS,mRS and TCM syndrome scores of both groups were significantly reduced after treatment(P<0.05),and the mRS and TCM syndrome scores of the intervention group were significantly lower than that of the control group(P<0.05),with the difference in mRS and TCM syndrome score before and after treatment being significantly higher than that of the control group(P<0.05).Regarding the comparison of coagulation function before and after treatment between the two patient groups,D-D and FIB indicators of both groups were significantly reduced after treatment(P<0.05),while PT and APTT indicators were significantly increased compared with before treatment(P<0.05).The APTT and FIB indicator results of the intervention group were better than those of the control group(P<0.05).The D-D,PT and TT showed no significant changes(P>0.05).Regarding the comparison of treatment efficacy between the two patient groups,the TCM efficacy showed a significant difference between the two groups with statistical significance(intervention group vs.treatment group,97.06%vs.79.41%,P<0.05),while there was no significant difference between the two groups in Western medicine efficacy(intervention group vs.treatment group,88.24%vs.70.59%,P>0.05).Regarding the comparison of recurrent stroke scores and 90-day recurrence rate between the two patient groups,there was no significant difference in ABCD2 score between the two groups.The 90-day recurrence rate of both groups of patients(intervention group vs control group,14.7%vs 23.5%,P>0.05)and related studies were similar.Conclusion:The Chinese herbal medicine HCSE,based on the method of replenish Qi and activate blood and expel stasis,significantly improved the symptoms of neurological function deficit caused by MIS on the basis of conventional treatment,and even more so in ischemic stroke patients presenting with Qi deficiency and blood stasis syndrome.Additionally,it improves patients’ coagulation function by increasing PT,APTT,and TT levels while decreasing FIB,further improving blood circulation without increasing bleeding risks.HCSE is safer and has no obvious adverse reactions,benefiting prognosis improvement.The exact mechanism of its action requires further exploration.