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Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis

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Journal of Integrative Medicine 2021年第2期19卷 144-157页

作者： Bing-rong Li Shi-yun Shao Long Yuan Ru Jia Jian Sun Qing Ji Hua Sui Li-hong Zhou Yi Zhang Hui Liu Qi Li Yan Wang Bi-meng Zhang Department of Acupuncture and Moxibustion Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function Fudan UniversityShanghai 200433China Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineDepartment of Medical Oncology&Cancer Institute of Integrative MedicineShuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China

Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorouracil(5-Fu).Methods:Forty male Sprague-Dawley rats were randomly divided into control,chemotherapy,moxibustion and probiotics groups.The IM rat model was established by intraperitoneal injection of 5-Fu.Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days.Tissue morphology,serum levels of inflammatory factors and the expression levels of tight junction proteins,caspase-1,gasdermin D and NLRP3 were evaluated in colon tissue,through hematoxylin and eosin staining,electron microscopy,enzyme-linked immunosorbent assay,Western blotting,quantitative realtime reverse transcription polymerase chain reaction and immunofluorescence.Gut microbiome profiling was conducted through 16 S rRNA amplicon sequencing.Results:Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins,reduced cell apoptosis and the expression levels of caspase-1,gasdermin D and NLRP3;they also decreased the serum levels of tumor necrosis factor-α,interleukin(IL)-6,IL-1βand IL-18,while increasing serum levels of IL-10.Moxibustion and probiotic treatments also corrected the reduction inα-diversity andβ-diversity in IM rats,greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapytreated rats to levels observed in healthy animals.We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors.Finally,moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.Conclusion:Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and

关键词： Chemotherapy Intestinal mucositis Moxibustion rats Microbiome NLRP3

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Role of epithelial-to-mesenchymal transition in the pulmonary fi brosis induced by paraquat in rats

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World Journal of Emergency Medicine 2021年第3期12卷 214-220页

作者： Jian-hua Yi Zhao-cai Zhang Mei-bian Zhang Xin He Hao-ran Lin Hai-wen Huang Hai-bin Dai Yu-wen Huang Emergency Department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Scientifi c Research Department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 301051China Shangyu People’s Hospital Shaoxing 312300China Pharmacy Department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China

BACKGROUND:This study aims to explore the characteristics of the epithelial-to-mesenchymal transition(EMT)process and its underlying molecular mechanisms in the period of paraquat(PQ)-induced pulmonary fi brosis(PF).METHODS:Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats.Immunohistochemistry,Western blot,and real-time reverse transcriptase-polymerase chain reaction(RT-PCR)were used to measure the protein and gene expression of EMT markers,EMT-associated transcription factors,and regulators of EMT-related pathways,respectively.RESULTS:The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF,reached a peak on day 14 after PQ poisoning,and then decreased on day 21.The protein and gene expression of the fibrosis marker,EMT markers,transcription factors,and regulators of EMT-related signaling pathways signifi cantly increased at diff erent time points after PQ poisoning compared with corresponding controls(P0.05).CONCLUSIONS:EMT process plays a role in the PQ-induced PF,in which most PF and EMT markers have a peak phenomenon,and its underlying molecular mechanisms might be determined by further studies.

关键词： Pulmonary fibrosis Paraquat Epithelial-to-mesenchymal transition rats

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Stem cell treatment improves post stroke neurological outcomes:a comparative study in male and female rats

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Stroke & Vascular Neurology 2021年第4期6卷 519-527,I0005-I0010页

作者： Koteswara Rao Nalamolu Bharath Chelluboina Casimir A Fornal Siva Reddy Challa David M Pinson David Z Wang Jeffrey D Klopfenstein Krishna Kumar Veeravalli Cancer Biology and Pharmacology College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Pharmaceutical and Biomedical Sciences California Health Sciences UniversityClovisCaliforniaUSA Neurological Surgery University of Wisconsin-MadisonMadisonWisconsinUSA Health Sciences Education College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Neurology College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Neurology Barrow Neurological InstitutePhoenixArizonaUSA Neurosurgery College of MedicineUniversity of IllinoisPeoriaIllinoisUSA OSF HealthCare Illinois Neurological Institute PeoriaIllinoisUSA Pediatrics College of MedicineUniversity of IllinoisPeoriaIllinoisUSA

Background and purpose The therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial.Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells(MSC)in a rodent stroke model.We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females,despite any apparent sex differences in post stroke brain injury.Methods Transient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery.Following the procedure,male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling.Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests(Modified Neurological Severity Score assessment,adhesive tape removal,beam walk and rotarod).The tests were administered at regular intervals(at days 1,3,5,7 and 14)after reperfusion to determine the time course of neurological and functional recovery after stroke.Results The infarct volume and extent of swelling of the ischaemic brain were similar in males and females.Despite similar pathological stroke lesions,the clinical manifestations of stroke were more pronounced in males than females,as indicated by the neurological scores and other tests.MSC treatment significantly improved the recovery of sensory and motor function in both sexes,and it demonstrated efficacy in both moderate stroke(females)and severe stroke(males).Conclusions Despite sex differences in the severity of post stroke outcomes,MSC treatment promoted the recovery of sensory and motor function in male and female rats,suggesting that it may be a promising treatment for stroke.

关键词： neurological female rats

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Impacts of exercise intervention on various diseases in rats

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Journal of Sport and Health Science 2020年第3期9卷 211-227页

作者： Ruwen Wang Haili Tian Dandan Guo Qianqian Tian Ting Yao Xingxing Kong School of Kinesiology Shanghai University of SportShanghai 200438China Division of Pediatric Endocrinology Department of PediatricsUCLA Children's Discovery and Innovation InstituteDavid Geffen School of Medicine at UCLALos AngelesCA 90095USA

Background:Exercise is considered as an important intervention for treatment and prevention of several diseases,such as osteoarthritis,obesity,hypertension,and Alzheimer's disease.This review summarizes decadal exercise intervention studies with various rat models across 6 major systems to provide a better understanding of the mechanisms behind the effects that exercise brought.Methods:PubMed was utilized as the data source.To collect research articles,we used the following terms to create the search:(exercise[Title]OR physical activity[Title]OR training[Title])AND(rats[Title/Abstract]OR rat[Title/Abstract]OR rattus[Title/Abstract]).To best cover targeted studies,publication dates were limited to"within 11 years."The exercise intervention methods used for different diseases were sorted according to the mode,frequency,and intensity of exercise.Results:The collected articles were categorized into studies related to 6 systems or disease types:motor system(17 articles),metabolic system(110 articles),cardiocerebral vascular system(171 articles),nervous system(71 articles),urinary system(2 articles),and cancer(21 articles).Our review found that,for different diseases,exercise intervention mostly had a positive effect.However,the most powerful effect was achieved by using a specific mode of exercise that addressed the characteristics of the disease.Conclusion:As a model animal,rats not only provide a convenient resource for studying human diseases but also provide the possibility for exploring the molecular mechanisms of exercise intervention on diseases.This review also aims to provide exercise intervention frameworks and optimal exercise dose recommendations for further human exercise intervention research.

关键词： Cancer Disease Exercise intervention Method rats System

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Neurological recovery and antioxidant effects of resveratrol in rats with spinal cord injury: a meta-analysis

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Neural Regeneration Research 2020年第3期15卷 482-490页

作者： Bao-Ping Xu Min Yao Zhen-Jun Li Zi-Rui Tian Jie Ye Yong-Jun Wang Xue-Jun Cui Spine Disease Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina Lu’an Hospital of Traditional Chinese Medicine Lu’anAnhui ProvinceChina Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education(Shanghai University of Traditional Chinese Medicine)ShanghaiChina Gansu Provincial Hospital of Traditional Chinese Medicine LanzhouGansu ProvinceChina Department of Orthopedics and Traumatology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina

Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as the main search terms,all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed,EMBASE,MEDLINE,Web of Science,Science Direct,China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases by computer.The search was conducted from their inception date to April 2017.No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations.Two reviewers independently selected studies according to the title,abstract and full text.The risk of bias in the included studies was also evaluated.Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso,Beattie,and Bresnahan scale score,inclined plane score and Gale’s motor function score.Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels,malondialdehyde levels,nitric oxide synthase activity,nitric oxide levels,xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor.The results of meta-analysis showed that compared with the control group,resveratrol significantly increased the Basso,Beattie,and Bresnahan scale scores after spinal cord injury(n=300,mean difference(MD)=3.85,95%confidence interval(CI)[2.10,5.59],P<0.0001).Compared with the control group,superoxide dismutase levels were significantly elevated(n=138,standardized mean difference(SMD)=5.22,95%CI[2.98,7.45],P<0.00001),but malondialdehyde levels were significantly diminished(n=84,SMD=–3.64,95%CI[–5.84,–1.43],P=0.001)in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurological recovery and exe

关键词： antioxidation meta-analysis neurological recovery pharmacotherapy rats resveratrol spinal cord injury systematic review

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The sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy

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Chinese Medical Journal 2020年第10期133卷 1203-1210页

作者： Wei Zhang Xiao-Dong Liu Jia-Wen Wang Ling-Feng Meng Yao-Guang Zhang Jian-Ye Wang Peking University Fifth School of Clinical Medicine Beijing 100730China Department of Urology Beijing HospitalNational Center of GerontologyBeijing 100730China.

Background:Dysuria is one of the main symptoms of genitourinary syndrome of menopause,which causes serious disruption to the normal life of peri-menopausal women.Studies have shown that it is related to decrease of detrusor contractile function,but the exact mechanism is still poorly understood.Previous results have suggested that the sphingosine-1-phosphate(S1P)pathway can regulate detrusor contraction,and this pathway is affected by estrogen in various tissues.However,how estrogen affects this pathway in the detrusor has not been investigated.In this study,we detected changes of the S1P/RhoA/Rho associated kinases(ROCK)/myosin light chain(MLC)pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.Methods::Thirty-six female Sprague-Dawley rats were randomly divided into SHAM(sham operation),OVX(ovariectomy),and E groups(ovariectomy+estrogen),with 12 rats in each group.We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting,respectively.We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay.Finally,we compared results between the groups with one-way analysis of variance.Results::The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased,as compared with SHAM group.The percent decreases of the components in the S1P pathway were as follows:sphingosine kinase 1(mRNA:39%,protein:45%)(both P0.05).The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows:ROCK2(protein:41%,mRNA:36%)(both P<0.0

关键词： Myosin light chains Ovariectomy rats Rho-associated kinases Sphingosine-1-phosphate Urinary bladder

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Protective roles of Vigna subterranea(Bambara nut) in rats with aspirin-induced gastric mucosal injury

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Journal of Integrative Medicine 2018年第5期16卷 342-349页

作者： Morufu Eyitayo Balogun Elizabeth Enohnyaket Besong Jacinta Nkechi Obimma Ogochukwu Sophia Mbamalu Fankou Serges Athanase Djobissie Department of Physiology Faculty of MedicineEbonyi State University Clinical Services Department National Obstetrics Fistula Centre

Objective： Vigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea （EEVS） was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay. Methods： Gastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. rats in Group I were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween B0 （ulcer group）, 20 mg/kg of omeprazole （positive group）, and 200 and 400 mg/kg of EEVS （experimental groups）, respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase （SOD）, glutathione peroxidase （GPx）, and malondialdehyde （MDA） in the gastric tissue homogenate were also determined. Results： Pretreatment with EEVS significantly （P 〈 0.05） reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly （P 〈 0.05） while the levels of SOD and GPx were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant （P〈0.05） protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group. Conclusion： The study suggests that EEVS offered a protective action against aspirin plus pylorus ligationinduced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytopro- tective and antioxidative mechanisms.

关键词： Vigna subterranea Anti-oxidative Aspirin plus pylorus ligation Gastric ulcers rats

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Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition:in vitro and in vivo study

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 25-33页

作者： Jia-Yi Jiang Wei-Ming Liu Qiu-Ping Zhang Hang Ren Qing-Ying Yao Gao-Qin Liu Pei-Rong Lu Department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Suzhou Center for Disease Prevention and Control Suzhou 215004Jiangsu ProvinceChina

AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.

关键词： diabetic model trimethylamine N-oxide inflammation endothelial dysfunction rats retinal microvascular endothelial cells

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Metabolic regulation mechanism of Aconiti Radix Cocta extract in rats based on ^(1)H-NMR metabonomics

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Chinese Herbal Medicines 2022年第4期14卷 602-611页

作者： Wenfang Jin Jianli Bi Sheng Xu Mengfan Rao Qi Wang Yan Yuan Baolei Fan Department of Medicine Hubei University of Science and TechnologyXianning 437000China The First People’s Hospital of Tongshan County Xianning 437000China Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province Xianning 437000China

Objective:To establish a metabonomics research technique based on the combination of^(1)H-NMR and multivariate statistical analysis,so as to explore the metabolic regulation mechanism of Aconiti Radix Cocta extract(ARCE)in rat tissues and serum.Methods:SD rats were randomly divided into blank group,female group and male group.The^(1)H-NMR technique was used to collect the information of rat tissues and serum samples in each group.The principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA)and other methods were used for data pattern recognition,so as to screen out potential differential metabolites and metabolic pathways,and then network analysis and KEGG database were used to analyze the relationship between metabolites,metabolic pathways and diseases.Results:The external features and^(1)H-NMR analysis showed that the sex of rats had no obvious effect on the drug action.A total of 15 potential differential metabolites and six metabolic pathways were screened out through data pattern recognition.Through network analysis and KEGG pathway analysis,three target diseases closely related to differential metabolites were found,and the metabolic pathway related to lung cancer was the central carbon metabolism of cancer.Conclusion:This study shows that Aconiti Radix Cocta(ARC)may regulate the energy metabolism of the body by influencing arginine synthesis,so as to play the roles of anti-inflammation,analgesia,anti-tumor and immune regulation.

关键词： Aconiti Radix Cocta ^(1)H-NMR metabolomics multivariate statistical analysis rats

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Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats

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Animal Models and Experimental Medicine 2021年第1期4卷 40-46页

作者： Vudhiporn Limprasutr Patrick Sharp Katechan Jampachaisri Cholawat Pacharinsak Sumit Durongphongtorn Department of Pharmacology and Physiology Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand Research Clusters:Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Chulalongkorn UniversityBangkokThailand Animal Resources Centre MurdochWAAustralia Department of Mathematics Faculty of SciencesNaresuan UniversityPhitsanulokThailand Department of Comparative Medicine School of MedicineStanford UniversityStanfordCAUSA Department of Veterinary Surgery Faculty of Veterinary ScienceChulalongkorn UniversityBangkokThailand

Background:Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats.The alpha-2 agonist,dexmedetomidine,has gained popularity in laboratory animal anesthesia.Tramadol is a weak opioid mu agonist.The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine(ZD)combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol(ZDT)in a minor procedure in rats.Methods:rats were induced with ZD or ZDT.After the loss of paw withdrawal,a small incision was made on the rats’left thighs as a surgical stimulus.rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes,then atipamezole was administered.Monitored anesthesia parameters included:(a)physiological parameters-pulse rate(PR),respiratory rate(RR),tissue oxygen saturation(%SpO 2),and body temperature;(b)duration parameters-induction time,onset and duration of surgical anesthesia plane,onset of recovery,and recovery time.Results:PR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups.No difference was observed for RR,%SpO 2,and body temperature.Likewise,there were no differences for duration parameters:induction time was less than 3 minutes;onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes,respectively;onset of recovery(time to move)was 51 minutes;and recovery time was 52 minutes,respectively.Conclusion:These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

关键词： anesthesia dexmedetomidine rats tiletamine tramadol

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