Clinical Study And Mechanism Of Xuebijing Injection In The Treatment Of Acute Lung Injury In Sepsis

Background:Sepsis,a syndrome characterized by organ dysfunction,arises from an imbalanced immune response to infection,thereby posing a significant risk to human well-being.The unregulated inflammatory reaction,triggered by a multitude of infectious or non-infectious factors,pervades the entirety of the sepsis pathological progression.The lung is frequently the primary site of sepsis initiation,as it is particularly vulnerable to inflammatory responses.Consequently,sepsis tends to accumulate in lung tissue,resulting in the development of acute lung injury(ALI).Clinical presentations often encompass progressive hypoxemia,which may progress to acute respiratory distress syndrome(ARDS).This condition can cause irreversible harm to lung tissue and contribute to heightened mortality rates.Notably,the clinical manifestations of acute respiratory distress syndrome are characterized by more severe and persistent hypoxemia and respiratory distress symptoms.Despite this,ARDS remains classified as a critical pathological form within the broader category of ALI.If the condition persists,it may progress to the point of developing multiple organ dysfunction syndrome(MODS)or multiple organ failure(MOF),which is recognized as a leading cause of mortality among critically ill individuals.Sepsis is identified as the predominant extrapulmonary factor contributing to the occurrence of ALI,accounting for a substantial proportion of cases ranging from 50%to 70%.The inflammatory factor storm plays a crucial role in the progression of sepsis to ALI,while the advancement of ALI or the exacerbation of hypoxemia during the ARDS process serves as a significant determinant for the impairment or potential failure of vital organs including the heart,liver,and kidney.Despite significant advancements in the understanding of the Pathophysiology of sepsis-associated ALI over the past decades,the current standard treatment options remain limited,primarily focusing on early anti-infection measures and lung protective ventilation strategies.Consequently,the timely intervention and treatment of ALI in sepsis hold immense importance in both the prevention and management of sepsis.Aims:(1)Preliminary identification of the main symptom distribution of ALI patients with sepsis through clinical cluster analysis.(2)This study employs a systematic assessment to examine the effectiveness and safety of Xuebijing Injection,a representative formulation utilized for the resolution of blood stasis and detoxification,in patients diagnosed with ALI.(3)This study aims to assess the clinical efficacy and prognostic impact of Xuebijing injection in the treatment of patients with sepsis-induced ALI.(4)This study aims to investigate the potential mechanism of Xuebijing injection in the treatment of septic ALI through the utilization of network pharmacology and Macromolecular docking technology.Methods:(1)The study involved the collection of four diagnostic information pertaining to traditional Chinese medicine symptoms and signs from a sample of 217 patients diagnosed with sepsis and ALI.These symptoms and signs were then subjected to statistical analysis using cluster analysis methods to evaluate their characteristics.The classification of traditional Chinese medicine symptoms was summarized based on the findings,and the distribution pattern of symptoms among patients with sepsis and ALI was determined.Additionally,the differences between different syndrome types of patients were assessed by analyzing the oxygenation index,white blood cell count,age,and prognosis of each patient category.(2)From the establishment of the database until December 31,2022,a randomized controlled clinical study was conducted to investigate the efficacy of Xuebijing injection in the treatment of ALI.Sixteen studies were ultimately included in the analysis,focusing on various parameters such as the oxygenation index,incidence of ARDS,all-cause mortality rate,and inflammatory factors(TNF and IL-6 levels)in ALI patients.The relative risk(RR)was employed as a categorical variable,while the standard average absolute deviation(SMD)was used as a continuous variable.The study employed the use of relative risk(RR)as a categorical variable and standard average absolute deviation(SMD)as a continuous variable.The effects model was examined through the application of either a fixed effects model or a random effects model,while a "funnel plot" was utilized to assess publication bias within the studies that were included.(3)A randomized controlled study was undertaken to investigate the effectiveness of Xuebijing injection in managing sepsis and ALI in a cohort of 30 patients.The study assessed the impact of Xuebijing injection on various parameters including respiratory function indicators,inflammatory indicators,APACHE Ⅱ score,SOFA score,duration of ICU hospitalization,and the cumulative survival rate at the end of 28 days post-treatment.(4)Utilizing a database for the acquisition of disease and drug targets,employing intersection analysis to identify potential therapeutic targets for the application of Xuebijing injection in the treatment of sepsis combined with acute lung injury,constructing a protein interaction network,and conducting topology analysis to screen for core targets.Employing the DAVID database for KEGG and GO enrichment analysis to identify pertinent pathways.The primary constituent of Xuebijing injection involved the utilization of macromolecular docking with the core target.Results:(1)By conducting cluster analysis on the Traditional Chinese Medicine(TCM)symptoms and signs exhibited by 217 patients diagnosed with sepsis-associated acute lung injury(ALI)as part of this study,in conjunction with expert opinions,three distinct syndromes were discerned.The initial syndrome identified was heat toxin syndrome,encompassing a total of 96 patients.The subsequent syndrome was blood stasis syndrome,comprising 72 patients.Lastly,deficiency syndrome was recognized as the third syndrome,affecting a total of 46 patients.There were no statistically significant differences observed in age,oxygenation index,white blood cell count level,SOFA score,APACHE II score,and 28-day cumulative survival rate among patients diagnosed with sepsis-induced acute lung injury across three distinct syndrome types.The pathological factors of "poison," "heat," "stasis,”and "deficiency" hold significant importance in patients experiencing acute lung injury resulting from sepsis.The theoretical feasibility of intervention therapy involving the resolution of blood stasis and detoxification emerges as a potential treatment approach for sepsis-induced acute lung injury.(2)According to a meta-analysis,the utilization of a combined approach involving traditional Chinese medicine,Western medicine intervention,and Xuebijing injection in the treatment of acute lung injury(ALI)demonstrates enhanced efficacy in reducing inflammatory factors in the peripheral blood of patients.Additionally,this approach improves the oxygenation index,decreases the occurrence of acute respiratory distress syndrome(ARDS),and significantly diminishes mortality rates.(3)Clinical studies have demonstrated that the administration of Xuebijing injection for the management of acute lung injury in sepsis yields significant improvements in respiratory function-related parameters,including enhanced oxygenation levels,rectification of tissue hypoxia,and reduced reliance on mechanical ventilation.Additionally,this intervention effectively mitigates the body’s inflammatory response,leading to a substantial reduction in the levels of C-reactive protein(CRP)and serum calcitonin,both of which are indicative of inflammation.The administration of Xuebijing injection has been found to decrease the duration of ICU hospitalization and mechanical ventilation usage in patients with sepsis-induced ALI.However,the findings of this study indicate that the implementation of Xuebijing intervention does not have a substantial effect on the mortality rate of these patients after 28 days,as evidenced by the lack of significant difference in the statistical outcomes.(4)The efficacy and characteristics of Xuebijing injection have been demonstrated through network pharmacology research,indicating its "multi component,multi target,and multi pathway" attributes.Quercetin,kaempferol,and luteolin are likely the primary active components of Xuebijing injection.Furthermore,ALB,AKT1,IL6,VEGFA,and IL1B are potential targets of Xuebijing injection in the treatment of sepsis with ALI,exerting their effects via the IL-17 and TNF signaling pathways.Research conclusion:(1)Sepsis ALI patients can be divided into three TCM syndrome types:"heat toxicity syndrome","blood stasis syndrome" and "deficiency syndrome".Clinically,"heat toxicity syndrome" and "blood stasis syndrome" are more common,and the severity and prognosis of patients with these three syndrome types are roughly the same.(2)The intervention of Xuebijing injection in the treatment of ALI is effective and safe.Xuebijing injection can effectively reduce the inflammatory factors in peripheral blood of ALI patients,improve the oxygenation index of patients and reduce the incidence of ARDS.The intervention of Xuebijing injection can also significantly reduce the mortality of ALI patients.(3)The results of clinical studies show that Xuebijing injection can improve the oxygenation index and other respiratory function related indicators and reduce the inflammatory response of the body,and has a certain degree of lung protection.(4)The possible mechanism of Xuebijing injection improving sepsis ALI is as follows:the main active components of Xuebijing injection(quercetin,kaemphamol and luteolin)may act on the potential targets of sepsis ALI(ALB,AKT1,IL6,VEGFA,IL1B)through IL-17 signaling pathway and TNF signaling pathway.