Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

Objective To explore the therapeutic effect of picroside Ⅱ(P Ⅱ)on diabetes nephropathy(DN)rats by regulating fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods A DN rat model was constructed by combining high sugar and high-fat diet with streptozotocin(STZ)injection.DN rats were grouped into model group(DN group),low,medium and high dose picroside Ⅱ groups(P-L group,P-M group,P-H group),and high dose picroside Ⅱ+Fas recombinant protein group(P-H+rh-Fas group),with healthy rats as control group,and 18 rats in each group.Fasting blood glucose(FBG),body mass,24-hour urinary protein(24h UTP),and renal function(SCr,BUN)were measured in rats.Hematoxylin-eosin(HE)staining and Masson staining were applied to observe the pathological changes in renal tissue of rats;immunohistochemistry and Western blot were applied to detect the expression of RAGE,COL-Ⅳ and pathway proteins,respectively.Results Compared with the control group,rats in DN group showed thickening of the glomerular basement membrane,mesangial proliferation,tubular degeneration,dilation,atrophy,fatty degeneration,obvious collagen deposition,higher levels of FBG,24h UTP,SCr,BUN,TNF-α,IL-6 and IL-1β,body mass loss,and higher expression of RAGE,COL-Ⅳ,Fas and FasL(P＜0.05).Compared with the DN group,the glomerular and tubular lesions were reduced and collagen deposition was decreased in the P-L,P-M and P-H groups,furthermore,the FBG,24h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were lower,body mass was higher,and the RAGE,COL-Ⅳ,Fas,FasL expression was lower(P＜0.05).Compared with the P-H group,the renal tissue lesions in the P-H+rh-Fas group worsened,the FBG,24 h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were higher,body mass was lower,and the RAGE,COL-Ⅳ,Fas,FasL expression was higher(P＜0.05).Conclusion Picroside Ⅱ exerts therapeutic effects on DN rats by inhibiting the Fas/FasL signaling pathway.

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Objective To explore the therapeutic effect of picroside Ⅱ(P Ⅱ)on diabetes nephropathy(DN)rats by regulating fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods A DN rat model was constructed by combining high sugar and high-fat diet with streptozotocin(STZ)injection.DN rats were grouped into model group(DN group),low,medium and high dose picroside Ⅱ groups(P-L group,P-M group,P-H group),and high dose picroside Ⅱ+Fas recombinant protein group(P-H+rh-Fas group),with healthy rats as control group,and 18 rats in each group.Fasting blood glucose(FBG),body mass,24-hour urinary protein(24h UTP),and renal function(SCr,BUN)were measured in rats.Hematoxylin-eosin(HE)staining and Masson staining were applied to observe the pathological changes in renal tissue of rats;immunohistochemistry and Western blot were applied to detect the expression of RAGE,COL-Ⅳ and pathway proteins,respectively.Results Compared with the control group,rats in DN group showed thickening of the glomerular basement membrane,mesangial proliferation,tubular degeneration,dilation,atrophy,fatty degeneration,obvious collagen deposition,higher levels of FBG,24h UTP,SCr,BUN,TNF-α,IL-6 and IL-1β,body mass loss,and higher expression of RAGE,COL-Ⅳ,Fas and FasL(P＜0.05).Compared with the DN group,the glomerular and tubular lesions were reduced and collagen deposition was decreased in the P-L,P-M and P-H groups,furthermore,the FBG,24h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were lower,body mass was higher,and the RAGE,COL-Ⅳ,Fas,FasL expression was lower(P＜0.05).Compared with the P-H group,the renal tissue lesions in the P-H+rh-Fas group worsened,the FBG,24 h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were higher,body mass was lower,and the RAGE,COL-Ⅳ,Fas,FasL expression was higher(P＜0.05).Conclusion Picroside Ⅱ exerts therapeutic effects on DN rats by inhibiting the Fas/FasL signaling pathway.

Objective:To investigate the effect of miR-425-5p on glucagon-like peptide-1(GLP-1) secretion in intestinal L cells induced by lipopolysaccharide(LPS), and to explore its mechanism.Methods:GLUTag cells of intestinal L cell line were incubated with LPS to determine the levels of miR-425-5p and GLP-1. Cell viability was determined by MTT assay, and cell apoptosis was detected by flow cytometry. Quantitative real time-PCR and western blot were performed to determine the expressions of miR-425-5p, phosphatase and tensin homology(PTEN), proglucagon, and GLP-1. Activity of Wnt/β-catenin signaling pathway was determined by detecting TOP/FOP ratio. Interaction among miR-425-5p, PTEN, and β-catenin was analyzed using luciferase activity assay and chromatin immunoprecipitation(ChIP)assay.Results:In GLUTag cells, with the elevation of LPS concentration, the expression of miR-425-5p and the apoptosis rate were increased, while the level of active GLP-1 and the cell viability were decreased. MiR-425-5p was involved in the regulation of LPS on GLP-1 secretion and intestinal L cell viability. Inhibition of miR-425-5p reduced the mRNA expression of proglucagon and the TOP/FOP ratio, increased PTEN protein level, and inhibited cell viability. In LPS-treated GLUTag cells, miR-425-5p increased the level of β-catenin by targeting PTEN, and β-catenin acted as a cis-acting element to induce the transcription of proglucagon and promote the secretion of GLP-1.Conclusion:In LPS-induced intestinal L cells, miR-425-5p promotes the expression of GLP-1 by targeting PTEN to modulate β-catenin.