| BackgroundSevere acute pancreatitis(SAP)is a common acute critical disease,and acute lung injury is one of the most common early complications.It is also the main cause of early high mortality.60% of SAP patients who died within 7 days of hospitalization died of respiratory failure.At present,there are more and more researches on the pathogenesis and clinical drug intervention of severe acute pancreatitis,but the exact pathogenesis is not fully understood.NF-kappa B,as the main regulator of the inflammatory response,plays a major role in the development of acute pancreatitis,and a number of studies have shown that inhibition of the activation of NFkappa B can significantly improve the severity of lung injury.Aromatic compound receptor(AhR),as a member of the basic spiral-cyclo-spiral transcription factor family,can interact with NF-kappa B to regulate its activity and inhibit the proliferation of inflammatory reactions.Therefore,it is important to study the role of AhR receptor in the pathogenesis of lung injury in acute pancreatitis.Qingyi Decoction is an effective prescription for the treatment of acute pancreatitis.Due to the general limitations of its clinical research,the sample volume is less and the conclusion is poor.Therefore,it is of certain clinical significance to evaluate its effectiveness in the treatment of pancreatitis.PurposeOn the one hand,systematic evaluation is used to analyze the effectiveness of Qingyi Decoction in the intervention of acute pancreatitis,so as to provide a more evidence-based medical basis for its clinical promotion;On the other hand,the effect of AhR receptor on lung injury in acute pancreatitis and the effect of Qingyi Decoction adding Polygonum cuspidatum(it contains resveratrol which is AhR antagonist)on the disease were studied by preparing the rat model of acute pancreatitis,and this is to provide a theoretical basis and experimental basis for finding a better prescription for treating acute lung injury caused by acute pancreatitis.Methods1 Clinical literature study: Retrieving PubMed,Embase,Cochrane Library,Chinese biomedical literature database(CBM),Chinese journal full text database(CNKI),Wan Fang(WanFang)and VP(VIP)database,manually supplemented the relevant important conference papers and publications.2 researchers screened literature,quality assessment and extracted basic information,research objects,intervention measures,outcome indicators and other literature information.The Cochrane migration risk assessment tool was used to evaluate the quality of the literature,and the software RevMan5.3 and stata14 were used for meta analysis.2 Animal experiment research:48 healthy male SPF SD rats were randomly divided into 6 groups,including sham operation group,model group,AhR agonist group(beta naphtha flavone treatment model group),AhR antagonist group(resveratrol treatment model group),Chinese medicine treatment group(treatment group of Qingyi Decoction adding Polygonum cuspidatum),medium model group,8 rats in each group.6h samples were collected after modeling: serum,bronchoalveolar lavage fluid and lung tissue.The general and gross anatomical features,the moisture / dry mass ratio of lung tissue,the pathological characteristics of lung tissue were observed by HE staining,the level of blood amylase was detected by ELISA,the percentage of neutrophils in the alveolar lavage fluid by Rayleigh staining,the protein content of alveolar lavage solution by BCA,the TUNEL assay was used to detect lung cell apoptosis,the protein expression level of NF-kappa B pathway related protein p65 in lung tissue was detected by immunohistochemis-try and Q-PCR method was used to detect mRNA expression level of NF-kappa B pathway related protein p65 and AhR target gene CYP1A1 in lung tissue.Results1 Clinical literature study : a total of 37 RCTs which met the inclusion criteria were included in the study and a total of 3165 patients were included in the study.Meta analysis results:(1)Modified Qingyi Decoction Combined with conventional western medicine in the treatment of acute pancreatitis in improving the efficiency is better than the simple use of conventional western medicine treatment(RR=1.13,95%CI[1.09,1.17],Z=6.59,P <0.00001).(2)the Modified QingYi Decoction combined with routine western medicine treatment can significantly reduce the mortality of patients with acute pancreatitis(RR=0.36.95%CI[0.24,0.53],P < 0.00001)and the rate of hospitalization time(MD=-5.52,95%CI[-6.20,-4.84],Z=15.93,P < 0.00001).(3)The combined effect of SAP in the subgroup of the average time of hospitalization was MDSAP=-5.99,the combined effect of MAP in the subgroup was MDMAP=-5.05,and the MDSAP > MDMAP.It can be seen that modified Qingyi Decoction combined with conventional western medicine treatment in the treatment of patients with severe acute pancreatitis is more effective in shortening hospital staying.2 Animal experiment research:(1)Construction and evaluation of animal model of acute pancreatitis with lung injuryCompared with the sham operation group,the rats in the animal model group with acute pancreatitis had a slow reaction,rapid respiration,and the pathological features of the lung tissue appeared bleeding,edema,alveolar septal destruction,neutrophils infiltration.The content of serum amylase and the ratio of wet / dry mass of lung tissue increased significantly(P < 0.05),and the percentage of neutrophils in the alveolar lavage fluid increased.These conform to the characteristics of the SAP-ALI.(2)The therapeutic effect of AhR agonist,antagonist and Qingyi Decoction adding Polygonum cuspidatum on the animal model of acute pancreatitis with lung injuryCompared with the model group,the rats of AhR agonists were almost inactive,breathing violently,and the pathological changes of lung tissue were aggravated.The blood amylase,wet / dry mass ratio of lung tissue,protein content of alveolar lavage fluid and lung tissue apoptosis index of lung increased(P < 0.05);Compared with the model group,the solvent group had no significant change in the above indexes(P>0.05);Compared with the model group,the rats of AhR antagonist group have moderate activity,faster respiratory frequency and less pathological changes in lung tissue,and the above indexes decreased(P<0.05);Compared with traditional Chinese medicine treatment group and model group,the rats have moderate activities,the respiratory rate was slightly faster,the pathological changes of lung were reduced,and the above indexes decreased(P <0.05);The changes of BALF neutrophilpercentage were the same as those of the above indexes in each group.(3)Immunohistochemistry was used to detect the protein expression level of NF-kappa B pathway related protein p65 in lung tissue of rats,and Q-PCR was used to detect the expression level of NF-kappa B pathway related gene p65 and AhR target gene CYP1A1 in each group.Compared with the model group,the expression level of NF-kappa B pathway related protein p65 protein expression level in AhR agonist increased(P < 0.05),the mRNA expression level of p65 gene and AhR target gene CYP1A1 increased(P < 0.05).Compared with the model group,there was no obvious change in the above indexes in the solvent group(P>0.05).Compared with the model group,the above indexes of AhR antagonist and Chinese medicine treatment group decreased(P < 0.05).Conclusions1.Modified Qingyi Decoction in the treatment of acute pancreatitis can significantly improve the efficiency,reduce the mortality,shorten the hospitalization time,and better effect on severe acute pancreatitis;2.The retrograde injection of 1.5% sodium deoxycholate to establish a lung injury model for severe acute pancreatitis is successful;3.The AhR antagonist(resveratrol)has a protective effect on SAP-ALI,and its mechanism may be by inhibiting the activation of the AhR-NF-kappa B signaling pathway and thus inhibiting the development of the inflammatory reaction,and the AhR agonist(beta naphthalene flavone)exactly reconfirms this result.4.The traditional Chinese Medicine Qingyi Decoction adding Polygonum cuspidatum may inhibit the activation of AhR-NF-kappa B signaling pathway and then alleviate the severity of SAP-ALI lung tissue damage.This experiment provides an experimental basis for the further improvement of the Qingyi Decoction. |
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