| Objective:Pseudomonas aeruginosa(PA)is distributed in nature,human skin and medical settings,causes lung infections when the human immune system is depressed,and is an important causative agent of hospital-acquired infections.With the increased application and irregular use of antibiotics,it has led to increasing drug resistance of PA,making clinical drug decisions more and more difficult and seriously threatening patients’ health.FuZheng TuoXie Decoction is a TCM treatment idea based on the theory of Fu-Xie and combined with the clinical characteristics of drug-resistant PA pneumonia.Previous studies have demonstrated that FuZheng TuoXie Decoction can increase the level of pro-inflammatory factors and help clear bacteria in the early stage of drug-resistant PA pneumonia,but there are fewer studies on the pro-inflammatory-anti-inflammatory balance of inflammation and the changes of inflammatory factors in different periods of inflammation.HMGB1(High mobility group box 1)is an important late inflammatory factor.Based on the previous research results,in order to further investigate the effect of FuZheng TuoXie Decoction on immune homeostasis and the molecular mechanism,we observed the effect of FuZheng TuoXie Decoction on the content of different inflammatory factors in different periods of time,and the effect of high mobility group protein 1(HMGB1),Toll like receptor 4(TLR4)and NF-κB(Nuclear factor kappa B)on immune homeostasis and HMGB1/TLR4/NF-κB signaling pathway..We also summarized the characteristics of TCM evidence and the rules of medication in drug-resistant PA pneumonia to provide a basis for the clinical diagnosis and treatment of drug-resistant PA pneumonia and to enrich the scientific connotation of the theory of Fu-Xie.Method:1.To analyze the TCM evidence characteristics of drug-resistant P.aeruginosa infection by collecting information on general conditions,laboratory tests,TCM four diagnosis information and referral of patients with P.aeruginosa lung infection hospitalized in Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine from January 2019 to December 2020.2.Screening the prescriptions of drug-resistant PA cases in the first part of the study,association rules and cluster analysis of the prescribed drugs were performed with the help of SPSS Modeler and SPSS.3.21 rats were randomly divided into blank group,model group and FuZheng TouXie group,the model group and FuZheng TouXie group were infected with drug-resistant PA by tracheal injection,the blank group and model group were gavaged with distilled water,and the FuZheng TouXie group was gavaged with FuZheng TouXie Decoction and the rats were executed after 3h,24h,3d,5d and 7d,respectively,and peripheral blood was collected to detect TNF-α,IL-10 and HMGB1 in peripheral blood by ELISA.In the rats executed at 7d,4 rats were randomly selected from each group and lung tissues were collected.lung tissues were examined for pathology by HE;HMGB1,TLR4 and NF-κB mRNA expression in lung tissues by RT-PCR;HMGB1,TLR4 and NF-κB protein expression in lung tissues by Western blot,and lung tissues by immunohistochemistry.Result:1.Among 88 patients with PA pneumonia,47 patients with drug-resistant PA pneumonia and 41 patients with PA pneumonia,most patients with drug-resistant PA pneumonia were elderly male patients,infected units were mainly from emergency ICU,encephalopathy department and respiratory department,most had a history of long-term bed rest,smoking,broad-spectrum antibiotic use,most hospitalizations were 1-3 times,most hospitalization days were distributed in 15-28 days,combined with 5-9 underlying diseases most Most of them are respiratory system,cardiovascular system and digestive system.Invasive operations were mainly indwelling gastric tube,indwelling urinary catheter and mechanical ventilation.The drug sensitivity rate was ranked as amikacin(bupropion)(91.49%),gentamicin(70.21%),piperacillin(51.06%),and drug resistance was ranked as amineptine(68.09%),imipenem(57.45%),and meropenem(51.06%).The inflammatory indexes were mostly normal WBC and elevated NE%and CRP.The mortality rate of drug-resistant PA pneumonia was 19.15%,with the highest mortality rate in the emergency ICU and encephalopathy unit,and general drug resistance and multi-drug resistance had no effect on mortality.In the four diagnostic information of TCM,the tongue is dominated by dark red,red and light red tongue,how much moss,yellowish moss,thin white moss and white moss,and the pulse is mostly stringy and smooth and sunken,and the split pulse is dominated by stringy,thin and smooth pulse.The basic elements of TCM symptoms are most common with mixed evidence of deficiency and reality,among which the actual evidence is dominated by phlegm and the deficiency evidence is dominated by qi deficiency.2.Through screening 56 effective prescriptions,after analysis,the drugs in the prescriptions were Glycyrrhiza glabra,Scutellaria baicalensis,Poria cocos,Atractylodes macrocephala,Radix et Rhizoma penicillata,Pericarpium chenopodium,Bitter almond and Astragalus membranaceus with the highest frequency,the drug efficacy was the highest in tonic for deficiency,phlegm,cough and heat,the medicinal properties were mainly warm,cold and flat,the taste was mainly sweet,pungent and bitter,and the normalizing meridians were mostly in the lung,spleen and stomach meridians,and 23 associated drugs were obtained through correlation analysis.Seven clusters of drugs were extracted by cluster analysis.3.At 3h,the level of TNF-α in peripheral blood was significantly higher in the FuZheng Touxie group than in the model group(P<0.05),and at 5d,the level of TNF-α in peripheral blood was significantly lower in the FuZheng Touxie group than in the model group(P<0.05).At 3d,the level of IL-10 in peripheral blood was significantly lower in the FuZheng Touxie group than in the model group(P<0.05).At 3d,the level of HMGB1 in peripheral blood was significantly higher in the FuZheng Touxie group than in the model group(P<0.05).In the HE pathological manifestation,the tracheal wall of the model group was congested and edematous,with a large number of inflammatory cells infiltrated and epithelial cells disordered and detached;the tube wall of the Fuzheng Touxie group was smoother than that of the model group,and the number of swelling,lumen narrowing and inflammatory cells infiltrated in the tracheal wall was significantly reduced compared with that of the model group.The expression of HMGB1,TLR4 and NF-κB mRNA in lung tissues of the model group was significantly higher than that of the blank group(all P<0.05),and the expression of HMGB1,TLR4 and NF-κB mRNA in lung tissues of the Fu Zheng TouXie Fang group was significantly lower than that of the model group(all P<0.05).HMGB1,TLR4 and NF-κB protein expressions were significantly higher in the model group than in the blank group(P<0.05),and HMGB1,TLR4 and NF-κB protein expressions were significantly lower in the Fu Zheng TouXie group than in the model group(P<0.05).Immunohistochemistry showed that HMGB1,TLR4 and NF-κB expression were enhanced in the model group compared with the blank group,and HMGB1,TLR4 and NF-κB expression were weakened in the Fu Zheng TouXie group compared with the model group.Conclusion:1.Patients with drug-resistant Pseudomonas aeruginosa pulmonary infection were predominantly male,with high age,mostly combined with multiple respiratory,cardiovascular and cerebrovascular diseases,and the departments were mainly distributed in emergency ICU,encephalopathy department and respiratory department,with many days of hospitalization,mostly involving invasive operations,and the drug sensitivity results showed that drug-resistant Pseudomonas aeruginosa pulmonary infection was sensitive to amikacin(butamycin)(91.49%),gentamicin(70.21%)susceptible and resistant to aminotransimide(68.09%),imipenem(57.45%)and meropenem(51.06%).The TCM symptoms were mainly characterized by phlegm and qi deficiency,with deficiency and real mixed symptoms.2.The analysis of the medication pattern shows that drug-resistant P.aeruginosa lung infection is mainly characterized by "deficiency,phlegm and stagnation",so the medication is mainly used to tonify Qi and invigorate Blood,strengthen the spleen and resolve phlegm,clear heat and promote the production of fluid,and also to promote the lung to relieve the symptoms and relieve Shaoyang.3.Fuzheng Touxie Decoction can increase the level of pro-inflammatory factor TNF-α in peripheral blood in the early stage and decrease the level of pro-inflammatory factor TNF-αand HMGB1 in the late stage,while increasing the level of anti-inflammatory factor IL-10 to maintain the immune homeostasis of the body.Fuzheng Touxie Decoction can reduce the level of HMGB1 in the lung tissue of drug-resistant Pseudomonas aeruginosa pneumonia,reduce the inflammatory cell infiltration in the lung tissue of rats,and improve the lung injury.Fuzheng Touxie Decoction can simultaneously reduce the mRNA and protein levels of HMGB1,TLR4 and NF-κB in lung tissues of rats with drug-resistant Pseudomonas aeruginosa pneumonia.Fuzheng Touxie Decoction may inhibit the development of advanced inflammation of drug-resistant P.aeruginosa pneumonia through the modulation of HMGB1/TLR4/NF-κB signaling pathway. |
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