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amitriptyline inhibits NLRP3 inflammasome activation via the ASM/CE pathway in a cell model of NAFLD

BIOCELL 2024年第5期48卷 759-769页

作者： QIN LIU CHUNYAN NIU QIANG ZHANG SHIQIN SUN YUE CHEN YONGQIANG SHI Shengli Clinical Medical College Fujian Medical UniversityFuzhou350001China Department of Gastroenterology Nanjing Lishui People’s HospitalZhongda Hospital Lishui BranchSoutheast UniversityNanjing211200China Department of Gastroenterology Yancheng Third People’s Hospital(The Yancheng School of Clinical Medicine of Nanjing Medical University)Yancheng224000China Administrative Department of Teaching and Scientific Research Nanjing Lishui People’s HospitalZhongda Hospital Lishui BranchSoutheast UniversityNanjing211200China

Background:Nonalcoholic fatty liver disease(NAFLD)is a global health concern with the acid sphingomyelinase(ASM)/ceramide(CE)pathway and the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)inflammasome identified as pivotal players in lipid disorders and *** study explores the interaction mechanism between the ASM/CE pathway and NLRP3 in NAFLD cell models,aiming to understand the impact of amitriptyline(Ami),an ASM inhibitor,on lipid deposition and hepatocyte injury by regulating the ASM/CE-NLRP3 ***:HepG2 and HL-7702 cells were exposed to free fatty acids(FFAs)to establish the NAFLD *** cells were divided into 5 groups:control group,model group,Ami group,tumor necrosis factoralpha(TNF-α)group,and Ami+TNF-α*** lipid droplets were visualized using Oil Red O staining,and Western blot analysis quantified ASM,NLRP3,and caspase 1 protein *** linked immunosorbent assay(ELISA)was measured CE and ASM levels,while qRT-PCR assessed mRNA *** apoptotic rate was evaluated by flow cytometry(FCM).Results:Following FFAs incubation,significant increases in ASM and CE levels were observed in HepG2 and HL-7702 cells,accompanied by elevated expression of NLRP3,and caspase 1,and IL-1β.TNF-αtreatment further amplified these *** demonstrated a reduction in lipid deposition,suppressed ASM/CE pathway activation,downregulated NLRP3 and caspase 1 expression,and improved ***,MCC950,a selective inhibitor of the NLRP3,mitigated NLRP3,caspase 1,and IL-1βexpression,alleviating lipid deposition and apoptosis in the NAFLD cell ***:The ASM/CE-NLRP3 pathway in NAFLD cells promotes hepatocyte steatosis,inflammation,and cell *** emerges as a promising therapeutic agent by inhibiting the ASM/CE-NLRP3 pathway,underscoring its potential as a key target for NAFLD treatment.

关键词： Nonalcoholic fatty liver disease Hepatocyte amitriptyline ASM/CE pathway NLRP3 Nonalcoholic steatohepatitis

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Sitagliptin,sitagliptin and metformin,or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats

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The Journal of Biomedical Research 2012年第3期26卷 200-210页

作者： Ashish Kumar Sharma Akash Sharma Rita Kumari Kunal Kishore Divya Sharma Bharthu Parthsarthi Srinivasan Ashok Sharma Santosh Kumar Singh Samir Gaur Vijay Singh Jatav Prashant Sharma Varnika Srivastava Sneha Joshi Megha Joshi Prashant Kumar Dhakad Davender Singh Kanawat Akanksha Mishra Anil Sharma Dharmendra Singh Ravinder Pal Singh Himmat Singh Chawda Rambir Singh Sachin Kumar Raikwar Muneem Kumar Kurmi Pankaj Khatri Ashutosh Agarwal Arshee Munajjam Department of Pharmacology Gyan Vihar School of PharmacySuresh Gyan Vihar UniversityJagatpuraJaipur(Rajasthan)302025India Department of Pharmacology Delhi Institute of Pharmaceutical Sciences&ResearchPushpviharNew Delhi 110017India Department of Pharmacology Kota Collage of PharmacyRIICO Industrial AreaRanpurKota(Rajasthan)Pincode 302025India

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neu- ropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide- streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly im- proved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 （P 〈 0.001）. Signif- icant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 （P 〈 0.001）. Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regen- eration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.

关键词： diabetic neuropathy nicotinamide-streptozotocin metformin pioglitazone glimipiride sitagliptin amitriptyline

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THE EFFECTS OF ELECTRO-ACUPUNCTURE VS. amitriptyline ON PLATELET 3H-PAROXETINE BINDING SITES IN DEPRESSED PATIENTS

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World Journal of Acupuncture-Moxibustion 1993年第1期3卷 49-51,56页

作者： Fan Xiaodong Shen Yucun Zhou Dongfeng Luo Hechun, Institute of Mental Health, Beijing Medical University, Beijing 10083, China

In this study platelet 3H-paroxetine binding site was studied in 16 depressed pa-tients and 16 healthy volunteers. We found that the mean Bmax of 3H-paroxetine binding on theplatelets of depressed patients was significantly lower than that of normal controls. After treated withamitriptyline or electro-acupuncture for 6 weeks, the density of paroxetine binding sites increased to-wards normal in well responded patients. But no significant difference was found between electro-acupuncture and amitriptyline as compared in their effects on 3H-paroxetine binding sites.

关键词： Electroacupuncture amitriptyline 3H-paroxetine binding sites Depressed diseases

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New Approach for the Determination of Tricyclic Antidepressant amitriptyline Using <i>β</i>-Cyclodextrin-PEG System via Spectrophotomerty

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Journal of Analytical Sciences, Methods and Instrumentation 2012年第2期2卷 103-107页

作者： Pankaj Soni Santosh K. Sar Rajmani Patel Department of Applied Chemistry Faculty of Engineering & Technology Shri Shankaracharya Group of Institutions Junwani Bhilai India Department of Engineering Chemistry Bhilai Institute of Technology Bhilai House Durg India

A new and simple procedure for the spectrophotometric determination of the tricyclic antidepressant drug amitriptyline is proposed. The method is based on enhancement of sensitivity of the [AMIYTP]+ β-cyclodextrin and PEG molecules involved in formation of molecules inclusion complex, in presence of polyethylene glycol (PEG) medium. The mole ratio of [AMIYTP]+ β-cyclodextrin and PEG molecules in inclusion complex were determined by the curve fitting method. The value of molar absorptivity of {[AMIYTP: (β CD)] PEG} complex in term of the drug lies in rage of (2.20 - 2.23) × 104 L·mole–1·cm–1 at absorption maximum 242 nm. The slope, intercept and correlation co-efficient were found to be 14.21, 0.0046, and 0.998, respectively. The effect of analytical variables on the determination of the drug and composition of the ion associated complex are discussed in the paper. This method is applicable in the determina-tion of amitriptyline in the pharmaceutical preparations.

关键词： amitriptyline PEG β-Cyclodextrin Spectrophotometric Determination AMIYTP-β-Cyclodextrin Complex Pharmaceuticals

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Electrocardiograms changes in children with functional gastrointestinal disorders on low dose amitriptyline

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World Journal of Gastroenterology 2014年第32期20卷 11321-11325页

作者： Ashish Chogle Miguel Saps Department of Pediatric Gastroenterology Hepatology and Nutrition Ann and Robert Lurie Children’s Hospital of Chicago Feinberg School of MedicineNorthwestern University Chicago IL 60611 United States

AIM: To study the effects of low dose amitriptyline on cardiac conduction in ***: Secondary analysis of data obtained from a double-blind, randomized placebo-controlled trial, evaluating low dose amitriptyline in children with a diagnosis of functional abdominal pain, functional dyspepsia, and irritable bowel syndrome according to the Rome II criteria. Children 8-17 years of age were recruited from the pediatric gastroenterology clinics of 6 tertiary care centers in the United States. The electrocardiograms(EKGs) done prior to initiation of amitrityline and 1 mo after initiation of amitriptyline were examined. The changes in cardiac conduction were evaluated in patients and controls. RESULTS: Thirty children were included in the study. There were 12 patients, ages 9-17 years of both genders, in the amitriptyline treatment group and 18 patients, ages 9-17 years of both genders, in the placebotreatment group. None of the patients had any baseline EKG abnormality. amitriptyline use was associated with an increase in heart rate(P = 0.024) and QTc interval(P = 0.0107) as compared to pre-EKGs. Children in the placebo group were also noted to present a statistically significant increase in QTc interval(P = 0.0498). None of the patients developed borderline QTc prolongation or long-QT syndrome after they were started on ***: The study findings suggest that once patients with functional gastrointestinal disorders have been screened for prolonged QTc interval on baseline EKG, they probably do not need a second EKG for reevaluation of cardiac conduction after starting low dose amitriptyline.

关键词： amitriptyline Electrocardiogram Children Abdominal

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Low-dose amitriptyline combined with proton pump inhibitor for functional chest pain

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World Journal of Gastroenterology 2013年第30期19卷 4958-4965页

作者： Se Woo Park Hyuk Lee Hyun Jik Lee Jun Chul Park Sung Kwan Shin Sang Kil Lee Yong Chan Lee Ji Eun Kim Department of Internal Medicine Institute of GastroenterologyYonsei University College of Medicine Biostatistics Collaboration Unit Yonsei University College of Medicine

AIM:To investigate the efficacy of amitriptyline with proton pump inhibitor(PPI)for the treatment of functional chest pain(FCP).METHODS:This was a randomized,open-label trial investigating the addition of low dose amitriptyline(10 mg at bedtime)to a conventional dose of rabeprazole(20 mg/d)(group A,n = 20)vs a double-dose of rabeprazole(20 mg twice daily)(group B,n = 20)for patients with FCP whose symptoms were refractory to *** primary efficacy endpoints were assessed by global symptom score assessment and the total number of individuals with > 50% improvement in their symptom ***:The between-group difference in global symptom scores was statistically significant during the last week of treatment(overall mean difference;3.75 ± 0.31 vs 4.35 ± 0.29,the between-group difference;P 50%,whereas only 26.3% of patients in group B had a similar treatment response(70.6% vs 26.3%,P = 0.008).Specifically,patients in group A had a significantly greater improvement in the domains of body pain and general health perception than did patients in group B(52.37 ± 17.00 vs 41.32 ± 12.34,P = 0.031 and 47.95 ± 18.58 vs 31.84 ± 16.84,P = 0.01,respectively).CONCLUSION:Adding amitriptyline to a PPI was more effective than a double-dose of PPI in patients with FCP refractory to a conventional dose of PPI.

关键词： Functional chest pain Proton pump inhibitor amitriptyline

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Effect of amitriptyline on gastrointestinal function and brain-gut peptides: A double-blind trial

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World Journal of Gastroenterology 2013年第26期19卷 4214-4220页

作者： Wei Huang Shu-Man Jiang Lin Jia Le-Qing You Yao-Xing Huang Yan-Mei Gong Gui-Qin Wang Department of Gastroenterology Guangzhou First People's Hospital Guangzhou Medical University Department of Radiology Guangzhou First People's Hospital Guangzhou Medical University Department of Statistics Guangzhou First People's Hospital Guangzhou Medical University

AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay ***: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.

关键词： amitriptyline Orocecal transit time Visceral hypersensitivity Gastric emptying Brain-gut peptides

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Effect of low-dose amitriptyline on globus pharyngeus and its side effects

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World Journal of Gastroenterology 2013年第42期19卷 7455-7460页

作者： Le-Qing You Jing Liu Lin Jia Shu-Man Jiang Gui-Qin Wang Department of Gastroenterology Guangzhou First People’s HospitalGuangzhou Medical University Department of Gastroenterology Guangzhou Nansha Central Hospital

AIM:To compare the efficacy and side effects of lowdose amitriptyline(AMT)with proton pump inhibitor treatment in patients with globus ***:Thirty-four patients who fulfilled the RomeⅢcriteria for functional esophageal disorders were included in this *** were randomly assigned to receive either 25 mg AMT before bedtime(AMT group)or 40 mg Pantoprazole once daily for 4 wk(conventional group).The main efficacy endpoint was assessed using the Glasgow Edinburgh Throat Scale(GETS).The secondary efficacy endpoints included the Medical Outcomes Study 36-item short form health survey[social functioning(SF)-36]and the Pittsburgh Sleep Quality *** response was defined as a>50%reduction in GETS *** patients entering this study recorded side effects at days 1,8,15,22 and 29 using a visual analogue ***:Thirty patients completed the *** 4 wk of treatment,the AMT group had a greater response than the conventional group(75%vs 35.7%,P=0.004).At day 3,the AMT group showed significantly more improvement than the Conventional group in GETS score(3.69±1.14 vs 5.64±1.28,P=0.000).After 4 wk of treatment,the AMT group showed significantly greater improvement in GETS score and sleep quality than the Conventional group(1.25±1.84 vs 3.79±2.33,4.19±2.07 vs 8.5±4.97;P<0.01 for both).Additionally,the AMT group was more likely than the Conventional group to experience improvement in the SF-36,including general health,vitality,social functioning and mental health(P=0.044,0.024,0.049 and 0.005).Dry mouth,sleepiness,dizziness and constipation were the most common side ***:Low-dose AMT is well tolerated and can significantly improve patient symptoms,sleep and quality of ***,low-dose AMT may be an effective treatment for globus pharyngeus.

关键词： amitriptyline Globus pharyngeus Side effect Pantoprazole Treatment response

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TOXIC EFFECT OF amitriptyline ON THE FECUNDITY,FERTILITY AND VIABILITY OF DROSOPHILA MELANOGASTER BY ADULT FEEDING

TOXIC EFFECT OF AMITRIPTYLINE ON THE FECUNDITY,FERTILITY AND...

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中国毒理学会第五次全国学术大会

作者： Mansour Nazari Dept.of Medical parasitology School of MedicineHamedan University of Medical SciencesHamedanIran

＜正＞amitriptyline is included in a group of medications classified as tricyclic *** fruit fly Drosophila,also known as the cinderella of genetics is one of the most extensively studied organism in different fields of research. This study is to evaluate the genotoxic effect of amitriptyline on fecundity,fertility and viability of ***(OK

关键词： amitriptyline Drosophila melanogaster toxicity.

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阿密曲替林(amitriptyline)对男性不育的精液的作用

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国际泌尿系统杂志 1981年第6期01卷 32-34页

作者： R. S Padron 罗钩乐

本文研讨了二十例男性不育并有精子过少精子无力症的病人用抗抑制药阿密曲替林对其精液的临床价值。全组病例的精液定量分析表明有较高的精子数,在治疗后正常的精子形态的此例增加和精液量的增加,和治疗前后的精子数成正比个别定性测定... 详细信息

本文研讨了二十例男性不育并有精子过少精子无力症的病人用抗抑制药阿密曲替林对其精液的临床价值。全组病例的精液定量分析表明有较高的精子数,在治疗后正常的精子形态的此例增加和精液量的增加,和治疗前后的精子数成正比个别定性测定表明精子数增加50％和活力增加35％。这可能是阿密曲替林对一些这样的病人的精液有利的作用。

关键词：男性不育精子过少病人男性生殖器疾病精液分析精子无力 amitriptyline

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