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A Serialized Study On The Regulation Of Sepsis Adaptive Immunity Based On The Principle Of Replenishing Qi And Removing Blood Stasis

Posted on:2022-01-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y HuangFull Text:PDF
GTID:1524307295988269Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
Objective: 1.Systematic evaluation and analysis of the clinical efficacy of the method of replenishing qi and removing blood stasis in the treatment of sepsis,providing methodological evidence for further clinical and experimental research;2.To explore the mechanism of Buyang Huanwu Decoction,a representative prescription for Yiqi Huayu,in regulating the immune function and killing response of patients with sepsis;3.To study the effect of Buyang Huanwu Decoction on the adaptive immune function of patients with sepsis,and evaluate the safety of Buyang Huanwu Decoction for patients with sepsis.Method:1.Meta-analysis is used to evaluate the clinical efficacy of Yiqi Huayu method in the treatment of sepsis,and randomized controlled clinical trials(Randomized Controlled Trials,RCT)on the treatment of sepsis by Yiqi Huayu method are collected by searching the database.Observe its outcome indicators,evaluate and assess risks,apply Rev Man5.3 software to complete statistical analysis,and perform safety analysis and sensitivity analysis,and use funnel chart to evaluate the potential publication bias of the main observation indicators;2.Use network pharmacology methods to study the potential mechanism of Buyang Huanwu Decoction on the immune function of sepsis at the molecular level,and use molecular docking,animal experiments and cell experiments to treat sepsis with Buyang Huanwu Decoction.Preliminary verification of the main targets and pathways of the disease;3.Through randomized,controlled trials,patients who meet the internal resistance of sepsis and blood stasis were divided into treatment group(Buyang Huanwu Decoction group)and complications(conventional treatment group).Observe the effects of Buyang Huanwu Decoction on sepsis.Patient Acute Physiology and Chronic Health Status Score II(APACHEII),Sequential Organ Failure Score(SOFA),TCM Syndrome Score,Total White Blood Cells(WBC),Percentage of Neutrophils(N%),Percentage of Lymphocytes(L%),High-sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),trans-blood lymphocyte subtype CD4 + T lymphocyte percentage(CD4 +%),CD8 + T lymphocyte percentage(CD8 +%),CD4 + / CD8 +,CD56 + 16(NK%)and CD14 + HLA-DR + / CD14 + percentage(HLA-DR +%)and serum disease factors(TNF-α,IFN-γ,IL-6,IL-10.TGF-β)level: impact,statistical analysis of the results,evaluation of the clinical effect of Buyang Huanwu Decoction in regulating the adaptive immune function of sepsis.Results: 1.A total of 27 RCT studies were included in the Meta-analysis,including 1792 patients.The results found that the total effective rate of treating sepsis with the method of replenishing qi and removing blood stasis was higher than that of the conventional treatment group,and it could reduce the 28-day mortality of patients with sepsis.Improving APACHEII score,SOFA score and TCM syndrome score can significantly reduce peripheral blood WBC,CRP,PCT,TNF-α,IL-6 levels in patients with sepsis,shorten PT,APTT,increase peripheral blood PLT levels,and reduce DDi level,lower Lac level;2.Through network pharmacology research,it is found that Buyang Huanwu Decoction regulates sepsis immune function and inflammatory response mainly through luteolin,isorhamnetin,β-sitosterol,baicalein,β-carotene,etc.The chemical composition regulates the PI3K-Akt signaling pathway,IL-17 signaling pathway,TNF signaling pathway,and key target genes such as MAPK1,AKT1,JUN,PIK3 CA,etc.;it is found through animal experiments that Buyang Huanwu Decoction induces lps The tissue structure of the spleen of sepsis rats has a protective effect,and Buyang Huanwu Decoction can effectively inhibit the serum inflammatory factors TNF-α,IL-6,IL-17 A,IFN-γ in sepsis rats induced by lps Release and expression of IL-6,IL-17 A,and NF-κB m RNA in the spleen;Buyang Huanwu Decoction has a certain inhibitory effect on the release of NO from mouse macrophages induced by LPS,but it has not been found to have a significant inhibitory effect on the PI3K/Akt\MAPKs\i NOS\NF-κB pathway;3.Clinical studies have found that Buyang Huanwu Decoction can effectively reduce the APACHEII score,SOFA score and TCM syndrome score of patients,and reduce the level of peripheral blood WBC count.Neutrophil percentage,increase lymphocyte percentage,CD4+T lymphocyte percentage,CD4+/CD8+,HLA-DR+ percentage,effectively reduce the release of serum inflammatory factors TNF-α,IFN-γ,IL-6,TGF-β,However,in terms of 7-day mortality rate and 28-day mortality rate,there is no significant difference between the addition of Buyang Huanwu Decoction and conventional Western medicine treatment.Conclusion: 1.Treatment of sepsis based on the principle of replenishing qi and removing blood stasis can effectively inhibit the release of inflammatory factors,improve coagulation function and tissue organ hypoperfusion,thereby reducing the APACHEII score,SOFA score and TCM syndrome score of patients with sepsis.It plays an effective role in the treatment of toxins;2.Through the use of network pharmacology methods,the effective components,targets and pathways of Buyang Huanwu Decoction in the treatment of sepsis were systematically analyzed,which revealed the potential of Buyang Huanwu Decoction in regulating the immune function and inflammatory response of sepsis The mechanism of action may be mainly through the regulation of PI3K-Akt signaling pathway,IL-17 signaling pathway,and TNF signaling pathway through key chemical components such as shikonin,isorhamnetin,β-sitosterol,baicalein,β-carotene,etc.The target genes such as MAPK1,AKT1,JUN,PIK3 CA,etc.play a role.Moreover,studies have found that Buyang Huanwu Decoction has a certain protective effect on the spleen structure of LPS-induced sepsis rats,and can effectively inhibit the immunity of sepsis rats through the IL-17A/NF-κB/IL-6 pathway And inflammation.Through cell experiments,it was found that Buyang Huanwu Decoction had a certain inhibitory effect on the release of NO from mouse macrophages induced by LPS,but it was not found to have a certain effect on PI3K/Akt\MAPKs\i NOS\NF-κB pathway.The obvious inhibitory effect provides a basis for further clinical research.3.Buyang Huanwu Decoction can effectively regulate the spleen of patients with sepsis The adaptive immune function weakens the pro-inflammatory and anti-inflammatory responses of patients with sepsis,which may delay the occurrence of immunosuppression.And it can effectively reduce the APACHEII score,SOFA score,and TCM syndrome scores of patients with sepsis,which proves that the addition of Chinese medicine for replenishing qi and removing blood stasis is more effective and has a certain degree of safety,but compared with simple conventional treatment,it does not significantly change the patient The final prognosis.
Keywords/Search Tags:Sepsis, Yiqi Huayu, Meta-analysis, Buyang Huanwu Decoction, Network pharmacology, Molecular docking, Randomized controlled trial
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