Study On The Clinical Efficacy And Mechanism Of Xuebijing Injection In Treating Acute Pancreatitis Based On Network Pharmacology Approach

Acute pancreatitis is an acute abdominal disease with multiple factors and complex pathogenesis.The incidence of acute pancreatitis is increasing worldwide,and the annual incidence ranges from 13 to 45 per 100000 people.In patients treated in hospital,acute pancreatitis was the most frequent principle discharge diagnosis in gastrointestinal disease.The causes of acute pancreatitis include gallstones,binge alcohol consumption,Hypertriglyceridemia,infection,overeating,pancreatic cancer and so on.Acute pancreatitis is characterized by rapid progression and multiple complications.If it is not diagnosed and treated in time,it may develop into systemic inflammatory response syndrome and multiple organ dysfunction syndrome,even life-threatening.At present,there is no universally recognized specific medicine for the treatment of acute pancreatitis,and most of the available treatment measures are supportive treatment and symptomatic treatment.Therefore,the development of safe and effective drugs for the treatment of acute pancreatitis is an urgent research topic for current medical science and technology workers.Xuebijing injection is a traditional Chinese medicine developed based on house of blood stasis-expelling decoction under the theoretical guidance of "treatment of bacteria-poisoninflammation" and "three syndrome and three methods".It is a standardized intravenous injection,which contains extracts from Carthamus tinctorius flowers,Paeonia lactiflora roots,Ligusticum chuanxiong rhizomes,Angelica sinensis roots and Salvia miltiorrhiza roots.Xuebijing injection has the effect of blood-invigorating and stasis-dissolving,meridian passage-dredging and poison-melting.It could inhibit oxidative stress and inflammatory,remove endotoxins,improve microcirculation and regulate immune function.The purpose of this study is to evaluate the efficacy of Xuebijing injection in the adjuvant treatment of acute pancreatitis and to explore the mechanism of Xuebijing injection in the treatment of acute pancreatitis,so as to provide a scientific basis for clinical treatment.According to whether the patients are combined with Xuebijing injection,the patients who meet the inclusion criteria are divided into the control group and observation group.The relevant laboratory indexes（serum amylase,white blood cells,C-reactive protein,ect.）,the clinical symptom relief time and hospital days were compared between two groups.Additionally,the active ingredients of Xuebijing injection and their targets through TCMS platform;OMIM and GenCards databases were applied to find the targets,which were related to acute pancreatitis;Venn analysis was used to investigate the overlapping targets between active ingredient’s targets and acute treatment-related targets,which were considered to be potential targets of Xuebijing injection for the treatment of acute pancreatitis;The proteinprotein interaction（PPI）network were constructed through the STRING platform to screen key targets of drug therapy;GO and KEGG pathway enrichment analyses were performed through METASCAPE online platform to investigate the molecular mechanisms and pathways of drug action.The last,inflammation model was established by inducing RAW264.7 macrophage cell line were stimulated with LPS in vitro.The MTT method was used to observe the cytotoxicity of Xuebijing injection;the levels of TNF-α、IL-1β、IL-6 in the cell supernatant were detected by Elisa;the mRNA expression of TNF-α、IL-1β and IL-6 were measured by RT-qPCR;the secretion of NO was measured by NO kits.The thesis concluded that Xuebijing injection combined with basic treatment was better than the basic treatment in lowering levels of serum amylase,inflammatory indicators（white blood cell count,the percent of neutrophils,C-reactive protein）,improving gastrointestinal function and hospital days in patients of acute pancreatitis.There was no statistical difference between the patients’ liver function indexes（alanine aminotransferase,aspartate aminotransferase,y-glutamyltransferase）and renal function indexes（serum creatinine and blood urea nitrogen）compared with the basic treatment group.It showed that Xuebijing injection could reduce the patient’s inflammatory response,significantly shorten the clinical symptom relief time and hospital days,and had no significant effect on the patient’s liver and kidney functions.Compared with western medicine alone,the combination of Xuebijing injection on the basis of Western medicine has significant advantages in the treatment of acute pancreatitis.Network pharmacology studies showed that Xuebijing had significantly therapeutic action for acute pancreatitis through the overall synergy of multiple bioactive ingredients,multiple pathways and multiple targets.The specific mechanism may be realized through regulating inflammation and immune response,cell growth,proliferation and apoptosis,lipid metabolism balance and calcium-related signaling pathways.It reflected the effectiveness of TCM in clinical treatment and the correctness of traditional Chinese medicine basic theory.The vitro studies showed that Xuebijing injection had no adverse effect on the viability of RAW264.7 cells in the concentration range of 5-20 μL/mL;Xuebijing injection significantly inhibited the secretion of TNF-α,IL-1β,IL-6 and NO in cell supernatant,downregulated the expression of TNF-α,IL-1β and IL-6 mRNA,and inhibit LPS-induced inflammation.In summary,Xuebijing injection has anti-inflammatory effect and may treat acute pancreatitis through multi-components,multi-targets and multi-pathways,it can provide a theoretical basis for the treatment of acute pancreatitis and the clinical application of Xuebijing injection.