Font Size: a A A

A Clinical And Mechanistic Study On The Treatment Of Pediatric Bacterial Pneumonia With Marenchinin Granule:Targeting The "Gut Microbiota-SCFAs-HDAC3/NF-κB" Axis

Posted on:2024-11-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:L WangFull Text:PDF
GTID:1524307367454154Subject:Pediatrics of traditional Chinese medicine
Abstract/Summary:PDF Full Text Request
1 Clinical Evaluation of Ma Xing Shi Gan Tang in the Treatment of Pediatric Bacterial PneumoniaObjective: To explore the clinical efficacy of the classical Chinese medicine formula Ma Xing Shi Gan Tang(MXSG)in treating pediatric bacterial pneumonia.Methods: A total of 132 patients with bacterial pneumonia were collected and divided into an exposure group(66 cases,3 dropouts)and a control group(66 cases,2 dropouts)based on whether MXSG was used.Patients in the exposure group received MXSG in addition to other treatments,while those in the control group received treatments excluding MXSG.Clinical cure rate,complete fever recovery time,and changes in traditional Chinese medicine(TCM)syndrome scores before and after treatment were evaluated to assess clinical efficacy.In the exposure group,10 cases treated solely with MXSG were extracted as subgroup 1,while in the control group,baseline data equivalent to subgroup 1 and treated solely with antibiotics were extracted as subgroup 2 for comparison of complete fever recovery time and changes in main TCM syndromes before and after treatment.Results: The cure rate in the exposure group was higher than that in the control group,but the difference was not statistically significant(P > 0.05).The complete fever recovery time in the exposure group was shorter than that in the control group,with a statistically significant difference(P < 0.001).While the TCM syndrome scores were comparable between the two groups for symptoms such as fever,dyspnea,mental state,and dry stools(P > 0.05),symptoms including cough,sputum,pulmonary auscultation,aversion to wind,sweating,throat redness,sleep,loose stools,and stool frequency showed greater improvement in the exposure group(P < 0.05).Subgroup analysis revealed no significant improvement in symptoms of loose stools and stool frequency in the control group(P > 0.05).There was no significant difference in complete fever recovery time between the two subgroups,and both demonstrated good efficacy in improving fever,dyspnea,and dry stools(P > 0.05).However,subgroup 1 showed better efficacy than subgroup 2 in symptoms of cough,sputum,pulmonary auscultation,loose stools,and stool frequency(P < 0.05).Subgroup 2 showed no improvement in symptoms of loose stools and increased stool frequency,with a possible worsening of loose stools(P < 0.05).Conclusion: Supplementing Ma Xing Shi Gan Tang in the treatment of pediatric bacterial pneumonia can reduce fever duration,improve external symptoms of the disease,enhance the quality of life prognosis,and regulate gastrointestinal symptoms in children with bacterial pneumonia,offering a certain therapeutic effect on antibiotic-associated diarrhea.2 Molecular Mechanism of Ma Xing Shi Gan Tang in Treating Pediatric Bacterial Pneumonia Revealed by PCR-DGGE Technology and Network Pharmacology AnalysisObjective: To investigate the molecular mechanism of MXSG in treating pediatric bacterial pneumonia.Methods: MXSG components were identified using high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS).In vivo experiments were conducted by establishing a mouse model of pneumonia using Streptococcus pneumoniae(S.pn)nasal instillation.The therapeutic effects of MXSG on pneumonia mice were evaluated using whole-body plethysmography(WBP),micro-computed tomography(Micro-CT),and hematoxylin-eosin(H&E)staining.PCR-DGGE technology was employed for diversity analysis of mouse cecal contents.Network pharmacology was used to analyze and screen potential targets of MXSG in treating pediatric bacterial pneumonia,and a component-target network was constructed for enrichment analysis.DGGE was used to detect cecal contents of mice in each group,and SCFAs in the mouse cecum were detected using an HP-INNOWAX column.Enzyme-linked immunosorbent assay(ELISA)was used to detect inflammatory factors,while malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)assay kits were used to measure oxidative stress levels in mouse lung tissues.Western blot was employed to detect relevant proteins to clarify the lung tissue protection and pathway activation status.Results: Experimental results showed that besides obvious lung injury,the diversity of cecal contents in S.pn model mice significantly decreased,particularly with a significant decrease in butyric acid and acetic acid content.After drug administration,mice given MXSG showed general improvement,while those given ceftriaxone may experience exacerbated diarrhea symptoms.Lung function tests revealed that MXSG at medium doses effectively improved lung function in model mice,with recovery almost comparable to that of the ceftriaxone group.Micro-CT and H&E results indicated that both medium and high doses of MXSG and ceftriaxone significantly alleviated pulmonary inflammation and tissue damage.Network pharmacology analysis revealed that the candidate targets of MXSG were closely related to corresponding inflammatory stimuli,bacterial-derived molecules,and regulation of chemical carcinogens-reactive oxygen species and SCFAs metabolism,which may be one of the molecular mechanisms by which MXSG improves bacterial pneumonia.DGGE detection results showed a decrease in cecal content diversity in the model group mice,while the MXSG group mice showed a significant increase in electrophoretic bands(P < 0.01),restoring microbial homeostasis.In contrast,the electrophoretic bands and brightness decreased in the ceftriaxone group(P < 0.01),suggesting that ceftriaxone may treat bacterial pneumonia by inhibiting bacterial growth.SCFAs detection results showed a significant increase in acetic acid and butyric acid levels in mouse cecal contents in the MXSG group compared to the model group(P < 0.01),while the ceftriaxone group showed a decrease(P <0.01).ELISA results demonstrated that MXSG significantly reduced the expression of inflammatory factors,which may be related to the increase in acetic acid and butyric acid levels in mouse cecal contents.MDA,SOD,and GSH assay kit results indicated that MXSG could reduce reactive oxygen species levels caused by S.pn infection.Western blot results revealed that MXSG could regulate the expression of key factors in the HDAC3/NF-κB signaling pathway to alleviate inflammation in lung-injured mice.Conclusion: Research on the therapeutic effects of MXSG,acetic acid,and butyric acid on S.pn mice under the DEPL mouse model indicates that one of the mechanisms by which MXSG improves bacterial pneumonia lung injury may be through promoting SCFAs production to regulate the HDAC3/NF-κB signaling pathway.3 Ma Xing Shi Gan Tang Alleviates Pulmonary Inflammation in Bacterial Pneumonia by Promoting SCFAs Metabolism to Improve Intestinal Microbial EcologyObjective: To verify the mechanism by which MXSG alleviates lung inflammation by promoting SCFAs metabolism to improve intestinal homeostasis.Methods: A depleted-gut(DEPL)mouse model was established using broad-spectrum antibiotics.H&E,ELISA,and Western blot were used to evaluate the protective effects of MXSG and SCFAs on S.pn-infected DEPL mouse pneumonia and verify whether MXSG regulates the HDAC3/NF-κB inflammatory pathway by promoting SCFAs production to alleviate inflammation.Results: Experimental results showed that under reduced intestinal microbiota,the therapeutic effect of MXSG on lung-injured mice was counteracted.H&E staining results showed that improvement of inflammation damage in S.pn-infected DEPL mice treated with MXSG was not significant.ELISA and Western blot results showed no significant difference in the expression of relevant inflammatory factors compared to the model group.However,treatment with butyric acid and acetic acid resulted in a significant decrease in the expression of relevant inflammatory factors and proteins compared to the S.pn+DEPL group.Conclusion: Studies on the therapeutic effects of MXSG,acetic acid,and butyric acid on S.pn-infected mice under the DEPL mouse model suggest that one of the mechanisms by which MXSG improves bacterial pneumonia lung injury may be through promoting SCFAs production to regulate the HDAC3/NF-κB signaling pathway.
Keywords/Search Tags:Bacterial pneumonia, MXSG, Streptococcus pneumoniae, HDAC3, Intestinal microbiota, SCFAs
PDF Full Text Request
Related items