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Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study
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作者 Song Zhang Xue Fang +7 位作者 Le Kang Xiang-Yu Sui Miao Liu Yu-Jia Luo Shuo Fu Zhao-Shen Li Sheng-BingZhao Yu Bai 《World Journal of Clinical Cases》 SCIE 2024年第5期891-902,共12页
BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whethe... BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whether the observations are causal because of confounding factors.AIM To investigate the causal associations between urate levels and IBD using bidirec-tional Mendelian randomization(MR).METHODS Independent genetic variants for urate levels and IBD were selected as instru-mental variables from published genome-wide association studies(GWASs).Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD(the UK Biobank,the FinnGen database and a large GWAS meta-analysis)and one for urate levels(a large GWAS meta-analysis).MR analyses included the inverse-variance-weighted method,weighted-median estimator,MR-Egger and sensitivity analyses(MR-PRESSO).A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.RESULTS Genetically higher serum urate levels were strongly associated with an increased risk of UC[odds ratio(OR):1.95,95%confidence interval(CI):1.86-2.05]after outlier correction,and the ORs(95%CIs)for IBD and CD were 0.94(95%CI:0.86-1.03)and 0.91(95%CI:0.80-1.04),respectively.Animal studies have confirmed the positive association between urate levels and UC.Moreover,genetically predicted IBD was inversely related to urate levels(OR:0.97,95%CI:0.94-0.99).However,no association was observed between genetically influenced UC or CD and urate levels.CONCLUSION Urate levels might be risk factors for UC,whereas genetically predicted IBD was inversely associated with urate levels.These findings provide essential new insight for treating and preventing IBD. 展开更多
关键词 Inflammatory bowel disease urate levels ANTIOXIDANT Mendelian randomization Single nucleotide polymorphism
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三味小方靶向URAT1有效成分分子对接研究
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作者 王卫京 杨乾栩 曾仲大 《生物化工》 CAS 2024年第2期116-119,共4页
目的:以URAT1(尿酸转运蛋白1)为靶点,利用分子对接,筛选出三味小方中抑制URAT1的有效成分。方法:用AlphaFold2.1对URAT1进行建模,利用ledock软件将土茯苓、威灵仙、萆薢三味中药的组分与URAT1进行对接,并与药物苯溴马隆进行比较,筛选出... 目的:以URAT1(尿酸转运蛋白1)为靶点,利用分子对接,筛选出三味小方中抑制URAT1的有效成分。方法:用AlphaFold2.1对URAT1进行建模,利用ledock软件将土茯苓、威灵仙、萆薢三味中药的组分与URAT1进行对接,并与药物苯溴马隆进行比较,筛选出活性较好的组分。结果:三味中药中有多种组分能够与URAT1活性口袋结合良好,形成多个氢键,有的还形成了π-π键。其中土茯苓苷B、恩比宁等22种组分对接打分值优于苯溴马隆。结论:三味小方中含有土茯苓苷B、恩比宁等22种分子对接结果优于苯溴马隆的组分。该药方能够抑制URAT1,降低尿酸浓度。三味中药中,土茯苓包含有效成分最多。 展开更多
关键词 痛风 urat1 尿酸 分子对接
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Highly specific characterization and discrimination of monosodium urate crystals in gouty arthritis based on aggregation-induced emission luminogens
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作者 Wenjuan Wang Guiquan Zhang +5 位作者 Ziyi Chen Hanlin Xu Bohan Zhang Rong Hu Anjun Qin Yinghui Hua 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2023年第6期704-717,共14页
Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation.The purpose of this study was to explore whether aggregation... Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation.The purpose of this study was to explore whether aggregation-induced emission luminogens(AIEgens)can be used for highly specific imaging of MSU crystals to assist in the diagnosis of gout.First,we developed a series of luminogens(i.e.,tetraphenyl ethylene(TPE)-NH_(2),TPE-2NH_(2),TPE-4NH_(2),TPE-COOH,TPE-2COOH,TPE-4COOH,and TPE-Ketoalkyne),each of which was then evenly mixed with MSU crystals.Next,optimal fluorescence imaging of each of the luminogens was characterized by a confocal laser scanning microscope(CLSM).This approach was used for imaging standard samples of MSU,hydroxyapatite(HAP)crystals,and mixed samples with 1:1 mass ratio of MSU/HAP.We also imaged samples from mouse models of acute gouty arthritis,HAP deposition disease,and comorbidities of interest.Subsequently,CLSM imaging results were compared with those of compensated polarized light microscopy,and we assessed the biosafety of TPE-Ketoalkyne in the RAW264.7 cell line.Finally,CLSM time series and three-dimensional imaging were performed on MSU crystal samples from human gouty synovial fluid and tophi.As a promising candidate for MSU crystal labeling,TPE-Ketoalkyne was found to detect MSU crystals accurately and rapidly in standard samples,animal samples,and human samples,and could precisely distinguish gout from HAP deposition disease.This work demonstrates that TPE-Ketoalkyne is suitable for highly specific and timely imaging of MSU crystals in gouty arthritis and may facilitate future research on MSU crystal-related diseases. 展开更多
关键词 GOUT Monosodium urate HYDROXYAPATITE TPE-Ketoalkyne Aggregation-induced emission Confocal laser scanning microscope imaging
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尿酸对老年膝骨关节炎病人软骨GLUT9、URAT1表达的影响 被引量:2
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作者 张雪梅 王忠丽 +4 位作者 王超 黄腾 张凯 聂倩 宋光耀 《实用老年医学》 CAS 2023年第3期287-290,共4页
目的探讨老年膝骨关节炎病人血清UA水平与软骨组织中UA转运蛋白的相关性。方法收集2018~2019年就诊于河北省人民医院骨科的老年膝骨关节炎(KOA)病人30例。以所有入选者UA中位数水平(254.6μmol/L)将病人分为血清UA<254.6μmol/L组(A... 目的探讨老年膝骨关节炎病人血清UA水平与软骨组织中UA转运蛋白的相关性。方法收集2018~2019年就诊于河北省人民医院骨科的老年膝骨关节炎(KOA)病人30例。以所有入选者UA中位数水平(254.6μmol/L)将病人分为血清UA<254.6μmol/L组(A组)和UA≥254.6μmol/L组(B组),检测并比较2组软骨组织中葡萄糖易化转运蛋白9(GLUT9)和尿酸盐转运蛋白1(URAT1)的mRNA和蛋白的表达水平。结果与B组相比,A组病人的体质量、BMI较小,VAS评分较低,差异均有统计学意义(P<0.05)。Pearson相关分析显示,VAS评分与UA水平呈正相关(r=0.396,P<0.05)。B组病人关节软骨中GLUT9、URAT1的mRNA和蛋白表达水平均较A组明显升高,差异有统计学意义(P<0.05)。结论UA水平的升高可能通过增加软骨中GLUT9及URAT1蛋白的表达,使软骨细胞内UA水平升高,诱导软骨细胞氧化损伤,从而参与KOA的发病。 展开更多
关键词 尿酸 膝骨关节炎 葡萄糖易化转运蛋白9 尿酸盐转运蛋白1
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Chicory (Cichorium intybus L.) inhibits renal reabsorption by regulating expression of urate transporters in fructose-induced hyperuricemia 被引量:12
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作者 Yu Wang Zhijian Lin +2 位作者 Bing Zhang Xiao Wang Mengzhen Chu 《Journal of Traditional Chinese Medical Sciences》 2019年第1期84-94,共11页
Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this proc... Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this process:urate transporter (URAT)1,glucose transporter (GLUT)9,organic anion transporter (OAT)1 and OAT3.Excessive fructose intake may result in increased serum urate levels.Chicory (Cichorium intybus L.) has been used as an edible vegetable and traditional Chinese medicine.Studies have shown that chicory is a promising anti-hyperuricemia agent and we explored the mechanism of its uricosuric effect via a renal pathway.Methods:Hyperuricemia was induced in rats by administration of 10% fructose.The uricosuric effect was evaluated by determining the serum urate level.Renal excretory function was detected by the clearance rate of creatinine,clearance rate of uric acid and histology.The location and expression of URAT1,GLUT9,OAT1 and OAT3 their mRNA expression in kidneys were analyzed.Results:Chicory decreased serum levels of urate and creatinine significantly,and promoted the clearance of creatinine and urate,as well as improving renal pathologic changes due to hyperuricemia.Chicory inhibited expression of URAT1 and GLUT9 markedly in a dosedependent manner,but showed no influence on expression of OAT1 or OAT3.Conclusion:Chicory might be a promising anti-hyperuricemia agent.It can promote renal excretion of urate by inhibiting urate reabsorption,which may be related to downregulation of mRNA and protein expression of URAT1 and GLUT9. 展开更多
关键词 CHICORY FRUCTOSE HYPERURICEMIA RENAL resorption urate transporters
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Determining the role for uric acid in non-alcoholic steatohepatitis development and the utility of urate metabolites in diagnosis:An opinion review 被引量:2
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作者 Paul Brennan Kathleen Clare +1 位作者 Jacob George John F Dillon 《World Journal of Gastroenterology》 SCIE CAS 2020年第15期1683-1690,共8页
There has long been a recognised association between non-alcoholic fatty liver disease(NAFLD)and the composite aspects of the metabolic syndrome.Part of this association highlighted the supposed co-existence of elevat... There has long been a recognised association between non-alcoholic fatty liver disease(NAFLD)and the composite aspects of the metabolic syndrome.Part of this association highlighted the supposed co-existence of elevated uric acid levels in those with NAFLD.There is interest in exploitation of this as a putative diagnostic and prognostic biomarker in NAFLD.Given the increased economic and health burden associated with the NAFLD epidemic,improved methods of population-based,minimally-invasive methods and biomarkers are clearly highly sought and necessary.In this opinion review we review the proposed role of uric acid in the pathogenesis of NAFLD and its potential utilisation in the diagnosis and monitoring of the disease process. 展开更多
关键词 Non-alcoholic FATTY LIVER disease Non-alcoholic steatohepatitis Uric acid urate Non-invasive fibrosis markers FATTY LIVER index
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Hearing loss due to urate deposition in the middle ear:A case report and literature review
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作者 M.Hoste M.Cabri-Wiltzer +2 位作者 S.Hassid J.-C.Degols J.Vilain 《Journal of Otology》 CSCD 2022年第1期50-53,共4页
Gout is the most common cause of monoarthritis in men occurring classically in the great toe and the knee.Extra-articular gout manifestations are rare.Only a few cases of head and neck urate crystals deposits have bee... Gout is the most common cause of monoarthritis in men occurring classically in the great toe and the knee.Extra-articular gout manifestations are rare.Only a few cases of head and neck urate crystals deposits have been described in the literature.Precipitations in the middle ear cause conductive hearing loss with common otoscopic anomalies and difficult imaging diagnosis.We report a case of a healthy 58-years-old man with a middle ear urate deposit causing a progressive hearing loss as the very first symptom of gout.The nature of the deposit was unsure on computer tomography(CT)due to atypical density.The final diagnosis was revealed after surgical procedure and histologic examination.A review of the literature is also presented.Seven cases of middle ear urate deposit as the first symptom of gout were found and compared.Progressive conductive hearing loss in middle-aged patients with abnormal otoscopy and middle ear atypical density mass on CT scan must lead to a minimal surgical procedure with a histologic examination to exclude urate crystals deposits. 展开更多
关键词 Hearing loss urate deposit GOUT Middle ear OTOSCOPY
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Therapeutic Mechanism of Santeng Dingtong Recipe (三藤定痛方) on Monosodium Urate Crystal-Induced Rabbit Arthritis
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作者 谢强敏 陈莹 +2 位作者 吴希美 陈季强 卞如濂 《Chinese Journal of Integrated Traditional and Western Medicine》 2003年第2期128-131,共4页
Objective: To study the therapeutic mechanism of Santeng Dingtong recipe (STDT) on monosodium urate crystal (MSU) induced rabbit arthritis Methods: Forty-two rabbits were randomly divided into six groups, 7 in each gr... Objective: To study the therapeutic mechanism of Santeng Dingtong recipe (STDT) on monosodium urate crystal (MSU) induced rabbit arthritis Methods: Forty-two rabbits were randomly divided into six groups, 7 in each group. Group 1 received 0.9% saline 2. 5 ml/kg per day by gastrogavage (ig) for 10 days; Group 2, 3 and 4 received STDT 0.125 g/kg, 1.0 g/kg and 8.0 g/kg per day respectively by ig for 10 days; Group 5 received colchicine 4. 5 mg/kg per day by ig for 4 days; and Group 6 was untreated. MSU crystals 10 mg /500ul containing polymyxin B 10 u/ml was injected into the knee joints of Group 1-5 to make rabbit arthritis models. Leukocytes in synovial lavage fluids was then counted and differentiated; pathological injury of synovial membranes was observed under HE staining; interleukin-1 beta (IL-1B), tumor necrosis factor alpha (TNFa) and leukotriene B4 (LTB4) content in synovial lavage fluids were determined by ELISA. Results: MSU caused a rapid leukocyte infiltration and increased production of IL-1B, TNFa and LTB4 2 hrs after intra-articular injection. STDT inhibited neutrophil infiltration in synovial fluids dose-dependently, protected the synovial membrane against pathological injury and reduced the production of IL-1B, TNFa and LTB4; while colchicine did not decrease the level of TNFa, but significantly inhibited neutrophil infiltration in synovial fluid and reduced the production of IL-11B and LTB4. Conclusion: STDT exerts an anti-inflammatory effect in rabbit model of acute MSU arthritis, its mechanism being probably due to the decrease of XL-1B, TNFa and LTB4 synthesis. 展开更多
关键词 Santeng Dingtong recipe COLCHICINE monosodium urate crystal RABBIT ARTHRITIS interleukin-1 beta tumor necrosis factor alpha leukotriene B4 enzyme linked immunosorbent assay
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Successful prevention of tumor lysis syndrome using recombinant urate oxidase in patient with metastasic and bulky prostate rhabdomyosarcoma
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作者 Atsuko Watanabe Ryuhei Tanaka 《Case Reports in Clinical Medicine》 2014年第1期18-22,共5页
Tumor lysis syndrome (TLS) is a life-threatening oncological emergency that frequently occurs in patients with hematological malignancies. It is becoming more common in patients with solid tumors because of advances i... Tumor lysis syndrome (TLS) is a life-threatening oncological emergency that frequently occurs in patients with hematological malignancies. It is becoming more common in patients with solid tumors because of advances in molecular targeted therapies. Recombinant urate oxidase (rUO) is effective at preventing and treating hyperuricemia, but clinicians who treat adult patients with solid tumors are generally not aware of this. In addition, the treatment guidelines for TLS do not include indications for rUO treatment for chemosensitive sarcoma. We report an adolescent case of metastatic rhabdomyosarcoma (RMS), in which clinical TLS was successfully prevented using rUO. A 16-year-old Japanese male suffered from urinary retention and bone pain and was diagnosed with prostate RMS combined with multiple bone metastases and bone marrow involvement. He was judged to be at high risk of clinical TLS because his prostate tumor was bulky and he displayed laboratory TLS. rUO was administered during chemotherapy. Soon after the initiation of chemotherapy, his disseminated intravascular coagulation (DIC) got worse, and his lactate dehydrogenase (LDH) level was elevated due to tumor lysis. However, his serum uric acid levels remained low, and he was prevented from falling into acute renal failure. The planned regimen was successfully completed without life-threatening complications, and the patient achieved a complete response after 2 courses of chemotherapy. The international TLS consensus panel developed recommendations for TLS prophylaxis, but did not define the TLS risk classification of RMS. We recommend that RMS should be treated like neuroblastoma because it grows rapidly and is highly chemosensitive. Our patient was considered to be indicated for rUO because he displayed urinary retention, DIC, and laboratory TLS before chemotherapy. These features might be useful as indications for rUO therapy, which can safely support chemotherapy. 展开更多
关键词 Tumor LYSIS Syndrome RECOMBINANT urate OXIDASE RHABDOMYOSARCOMA
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Urate Transporter 1 Protein Levels and Localization in Type 2 Diabetic and Non-Diabetic Zucker Rat Kidneys
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作者 Yuriy Slyvka Felicia V. Nowak +4 位作者 William Matthew Wooten Kelly D. McCall Ramiro Malgor Aaron S. Wood Sharon R. Inman 《Open Journal of Endocrine and Metabolic Diseases》 2013年第1期63-68,共6页
Objective: Persons with type 2 diabetes have increased incidence of hyperuricemia and gout. The hypothesis that Urate transporter 1 (URAT1) levels are increased in type 2 diabetic Zucker rats and this is responsible f... Objective: Persons with type 2 diabetes have increased incidence of hyperuricemia and gout. The hypothesis that Urate transporter 1 (URAT1) levels are increased in type 2 diabetic Zucker rats and this is responsible for elevation of uric acid was tested. Methods: Male 12-week-old obese Zucker rats were compared to non-diabetic lean counterparts. Plasma glucose, uric acid and creatinine were measured. URAT1 protein levels in the renal cortex and medulla were determined by Western blot. Immunohistochemistry was used to determine the location of URAT1 inrenal tubules. Results: Plasma glucose and uric acid levels were higher in the diabetic rats. There was no difference in plasma createnine. URAT1 antibody-positive bands of 27, 31, 50, 62 and 70 kDa were observed in cortex. A similar pattern was observed in medulla with addition of a 44 kDa band. No differences were observed in URAT1 proteins in the cortex between obese and lean rats. In the medulla, expression of the 44 and 50 kDa proteins was higher in lean rats. Expression of 27, 50, 62 kDa URAT1 proteins in the cortex was higher than in the medulla, while expression of the 70 kDa URAT1 was higher in medulla than in cortex. Localization of URAT1 did not differ between groups and included tubules in both cortex and medulla. Conclusions: In male Zucker rats, URAT1 protein expression was observed in both kidney cortex and medulla. Uric acid elevation in the obese group was associated with decreases in the 44 and 50 kDa URAT1 proteins in renal medulla. 展开更多
关键词 urat1 TRANSPORTER Uric Acid ZUCKER Rat TYPE 2 Diabetes Gout
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高尿酸血症患者URAT1基因rs524023位点多态性检测及临床意义 被引量:3
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作者 范俊 柏晓松 熊世力 《海南医学》 CAS 2023年第7期987-990,共4页
目的检测高尿酸血症(HUA)患者人尿酸盐转运子(URAT1)基因rs524023位点多态性并探讨其临床意义。方法将2019年3月至2021年4月在上海市宝山区罗店医院进行健康体检的200例体检者纳入研究,详细记录所有体检者的一般资料,采集其血液样本检... 目的检测高尿酸血症(HUA)患者人尿酸盐转运子(URAT1)基因rs524023位点多态性并探讨其临床意义。方法将2019年3月至2021年4月在上海市宝山区罗店医院进行健康体检的200例体检者纳入研究,详细记录所有体检者的一般资料,采集其血液样本检测血生化指标和URAT1基因rs524023位点多态性。依据是否合并HUA分为合并HUA组47例和不合并HUA组153例,比较两组受检者的临床资料、URAT1基因rs524023位点等位基因和基因型频率分布,采用多因素Logistic回归分析URAT1基因rs524023位点多态性和HUA影响因素的交互作用。结果合并HUA组和未合并HUA组受检者在年龄、体质量指数(BMI)、血尿酸(SUA)、肌酐(Scr)、血尿素氮(BUN)、甘油三酯(TG)和肾小球滤过率(eGFR)水平方面比较差异均有统计学意义(P<0.05);在URAT1基因rs524023位点上,合并HUA组和未合并HUA组受检者的等位基因C、T的频率分别为27.66%、72.34%vs 41.83%、58.17%,基因型CC、TC、TT的频率分别10.64%、51.06%、38.30%vs 28.10%、37.91%、33.99%,差异均有统计学意义(P<0.05);年龄、BMI、高血脂和慢性肾病是影响HUA发病的影响因素,URAT1基因rs524023位点多态性与BMI≥25 kg/m^(2),合并高血脂和慢性肾病等HUA发病影响因素在相乘模型中存在交互作用(OR'值分别为0.81、1.17、1.57、2.16,P'值分别为0.31、0.03、0.03、0.02),增加了HUA的发病风险。结论URAT1基因rs524023位点突变可能会增加HUA发生的概率,且与BMI、高血脂和慢性肾病之间存在交互作用。 展开更多
关键词 高尿酸血症 人尿酸盐转运子基因 rs524023位点 单核苷酸基因多态性 肾脏功能
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Galangin probably ameliorates hyperuricemia by inhibiting urate acid transport 1 (URAT1): Homology modeling and mechanism exploration
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作者 Aijinxiu Ma Fuqi Wang Xu Zhao 《Journal of Polyphenols》 2022年第1期55-63,共9页
Urate acid transporter 1(URAT1)is the main transporter of uric acid reabsorption,which closely related to the pathogenesis of hyperuricemia.Screening URAT1 inhibitors and studying their possible metabolic processes is... Urate acid transporter 1(URAT1)is the main transporter of uric acid reabsorption,which closely related to the pathogenesis of hyperuricemia.Screening URAT1 inhibitors and studying their possible metabolic processes is a hot spot in the development of uric acid-lowering drugs.Studies have shown that many food-borne plant polyphenols have uric acid lowering activity with non-toxic side eff ects,and can be used to improve and alleviate hyperuricemia.In this study,we take galangin(GAL)as an example to explore the mechanism of plant polyphenols aff ecting hyperuricemia by inhibiting URAT1.Homology modeling was used to construct a three-dimensional model of URAT1 protein,and the structure was optimized.Ramachandran diagram was used to verify the rationality of model protein structure.A known URAT1 inhibitor,benzbromarone(BBR),was used to dock with URAT1 to determine the docking site and show the key amino acids.GAL and model protein were docked by molecular docking method to analyze their interaction.Meanwhile,comparing the interaction of BBR and GAL with the key amino acids of model proteins,the binding of GAL was more stable,suggesting that GAL could aff ects hyperuricemia by inhibiting URAT1.This paper aims to provide theoretical guidance for the development of new functional food ingredients for lowering uric acid. 展开更多
关键词 plant polyphenols GALANGIN urat1 HYPERURICEMIA homology modeling
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痛风基因表达谱的差异基因表达及免疫细胞浸润分析 被引量:1
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作者 陈锋 李华南 +3 位作者 章晓云 黄慧莲 陈跃平 任国武 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第3期592-598,共7页
目的:研究痛风患者的差异基因表达及免疫细胞浸润情况,寻找痛风发病的关键基因及免疫细胞,探究免疫细胞与痛风的关系。方法:从GEO数据库下载痛风的芯片GSE160170,借助R语言筛选差异基因,随后采用STRING数据库对差异基因进行分析,并借助C... 目的:研究痛风患者的差异基因表达及免疫细胞浸润情况,寻找痛风发病的关键基因及免疫细胞,探究免疫细胞与痛风的关系。方法:从GEO数据库下载痛风的芯片GSE160170,借助R语言筛选差异基因,随后采用STRING数据库对差异基因进行分析,并借助Cytoscape软件筛选关键基因,再对其进行富集分析,同时对免疫细胞浸润情况进行分析。结果:研究发现IL-6、IL-1β、TNF、CCL3、CXCL8和CXCL1为痛风发病的关键基因,主要通过IL-17、Toll样受体、NOD样受体、NF-κB等信号通路发挥细胞对脂多糖、细菌来源分子及生物刺激的反应等过程导致疾病发生;免疫浸润结果表明记忆性B细胞、活化的NK细胞、活化的树突状细胞、活化的肥大细胞和嗜酸性粒细胞在痛风患者中表达显著;免疫细胞间的相关性分析结果表明滤泡辅助性T细胞与活化的肥大细胞表达呈正相关,未活化的NK细胞与单核细胞表达呈负相关。结论:关键基因和差异表达的免疫细胞与痛风发病机制密切相关,为痛风的免疫机制研究提供了新思路。 展开更多
关键词 痛风 单钠尿酸盐 生物信息学 免疫细胞 细胞浸润
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云南地区hURAT1基因rs505802、rs3825016、rs3825017多态性与肺结核患者服用吡嗪酰胺致高尿酸血症的相关性研究
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作者 李先蕊 刘晖 +5 位作者 张文林 王俊龙 伍蓉霜 李谢 余春红 彭江丽 《临床肺科杂志》 2023年第4期493-499,共7页
目的探讨中国云南地区汉族人群人尿酸盐转运蛋白1(human urate transporter 1,hURAT1)基因rs505802、rs3825016及rs3825017单核苷酸多态性(single nucleotide polymorphism,SNP)与肺结核患者服用吡嗪酰胺导致高尿酸血症的相关性。方法选... 目的探讨中国云南地区汉族人群人尿酸盐转运蛋白1(human urate transporter 1,hURAT1)基因rs505802、rs3825016及rs3825017单核苷酸多态性(single nucleotide polymorphism,SNP)与肺结核患者服用吡嗪酰胺导致高尿酸血症的相关性。方法选取2019年1月至2021年10月期间在昆明市第三人民医院结核科住院治疗的294名服用吡嗪酰胺导致高尿酸血症的肺结核患者和220名服用吡嗪酰胺未导致高尿酸血症的肺结核患者作为研究对象。通过病例对照研究的方法,对所有研究对象进行生化指标测定,并通过全血DNA提取、SNP Sequenom MassARRAY分型检测、SNP genotype分析。计量资料符合正态分布用t检验,计数资料用χ^(2)检验,采用Logistic回归分析hURATl基因rs505802、rs3825016、rs3825017多态性与肺结核患者服用吡嗪酰胺导致高尿酸血症的相关性。结果治疗前后PIHU组与对照组的血尿酸差值比较差异有统计学意义(P<0.05)。rs505802、rs3825016、rs3825017位点CC基因型分布频率在PIHU组和对照组中差异均有统计学意义(P<0.05),PIHU组的C等位基因频率显著高于对照组,P值分别为<0.001(χ^(2)=13.489)、0.001(χ^(2)=11.479)和0.007(χ^(2)=7.287)。rs505802、rs3825016、rs3825017位点携带C等位基因的肺结核患者发生吡嗪酰胺诱导的高尿酸血症的风险均增加(OR=0.586,95%CI:0.440~0.780,P<0.001)、(OR=0.606,95%CI:0.453~0.811,P=0.001)、(OR=0.691,95%CI:0.528~0.904,P=0.007)。结论云南地区hURAT1基因rs505802、rs3825016及rs3825017位点的多态性与肺结核患者服用吡嗪酰胺导致的高尿酸血症有关,且等位基因C可能是其危险因素。 展开更多
关键词 单核苷酸多态性 人尿酸盐转运蛋白1 吡嗪酰胺 高尿酸血症
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痛风病中医认识源流考
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作者 张冰 胥亦 +1 位作者 林志健 王雨 《世界中医药》 CAS 北大核心 2024年第13期1875-1880,1888,共7页
痛风病是与高尿酸血症、尿酸盐沉积密切相关的慢性、进展性、致残性代谢疾病。本文旨在系统梳理痛风病各阶段相关的中医药古籍记载,厘清其中医药认识发展脉络,明确各时期对痛风病的认知及其特点,为痛风病深入研究和临床防治提供中医药... 痛风病是与高尿酸血症、尿酸盐沉积密切相关的慢性、进展性、致残性代谢疾病。本文旨在系统梳理痛风病各阶段相关的中医药古籍记载,厘清其中医药认识发展脉络,明确各时期对痛风病的认知及其特点,为痛风病深入研究和临床防治提供中医药理论支撑。通过查阅先秦至明清时期中医医论、方书、本草及医案106部,从中归纳整理有关痛风病的中医药认识,包括病名、症状、病因病机及治疗用药等,探析其发展源流。先秦时期,中医药古籍零星记载了痛风病各阶段的症状、病名和(或)病因病机;汉至隋唐,医家在扩充病名、症状及病因病机的基础上,提出了多种内外治法,标志着痛风病理论形成;宋元明清,证候分型、鉴别诊断及饮食禁忌等论述丰富了这一理论。中医药对痛风病的认识萌芽于先秦,理论形成于汉至隋唐,丰富发展于宋元明清,逐渐形成了一套较为全面的痛风病中医理论体系。 展开更多
关键词 痛风病 高尿酸血症 尿酸盐沉积 痛风性关节炎 代谢性疾病 中医理论 中医古籍 源流
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基于xCell算法研究痛风的免疫生物标志物及相关靶向中药的筛选
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作者 李玲琴 周睿姣 +1 位作者 张燕妮 袁心柱 《中国药师》 CAS 2024年第6期1007-1018,共12页
目的研究痛风致病的关键基因以及免疫生物标志物,挖掘潜在的靶向中药,为痛风的临床治疗提供新方向。方法从GEO数据库下载痛风芯片数据集,使用R软件进行差异基因的筛选,并对这些差异基因进行GO及基因通路KEGG富集分析。应用STRING数据库... 目的研究痛风致病的关键基因以及免疫生物标志物,挖掘潜在的靶向中药,为痛风的临床治疗提供新方向。方法从GEO数据库下载痛风芯片数据集,使用R软件进行差异基因的筛选,并对这些差异基因进行GO及基因通路KEGG富集分析。应用STRING数据库对差异基因进行蛋白质互作网络分析,利用Cytoscape筛选关键基因。使用ELISA方法对关键基因的蛋白表达水平进行实验验证。进一步使用xCell估计免疫细胞在痛风中的相对表达情况及相关性,最后通过Coremine Medical数据库对显著富集的免疫相关生物学过程及关键基因中药进行预测。结果筛选出痛风差异基因共计852个。在GO富集分析中,与免疫反应密切相关的主要生物学过程包括白细胞的趋化性、IL(白细胞介素)-2的产生以及血管生成的调控;KEGG通路主要富集于IL-17信号通路、趋化因子信号通路和肿瘤坏死因子(TNF)信号通路等。筛选出TNF、IL-6、IL-1β、趋化因子配体8(CXCL8)、FOS原癌基因(FOS)和血管内皮生长因子A(VEGFA)等10个关键蛋白,实验验证关键基因蛋白表达水平与芯片数据的表达趋势一致。免疫分析显示,单核细胞、记忆B细胞、初始CD8+T细胞和树突状细胞与痛风关系密切。中药预测发现,人参、三七、黄芩、三白草和丹参等为治疗痛风的潜在药物。结论本研究揭示了痛风致病的可能关键基因以及免疫机制,挖掘出潜在的靶向中药。这些关键基因和中药有望为痛风的治疗提供新的思路和方法。 展开更多
关键词 痛风 中药 生物信息学 免疫标志物 关节炎 代谢综合征 单钠尿酸盐 基因芯片
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基于TOE框架的煤矿事故致因组态研究
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作者 李琰 冯园 《煤矿安全》 CAS 北大核心 2024年第2期244-249,共6页
为了深入探究煤矿事故致因因素及组态路径,预防煤矿事故发生;以40起煤矿事故为研究对象,运用扎根理论识别煤矿事故致因因素,基于TOE(技术、组织、环境)框架构建煤矿事故致因模型,应用模糊集定性比较分析法(fsQCA)找出煤矿事故致因的组... 为了深入探究煤矿事故致因因素及组态路径,预防煤矿事故发生;以40起煤矿事故为研究对象,运用扎根理论识别煤矿事故致因因素,基于TOE(技术、组织、环境)框架构建煤矿事故致因模型,应用模糊集定性比较分析法(fsQCA)找出煤矿事故致因的组态路径和核心条件;在组态类型和核心条件基础上,提出预防煤矿事故发生的建议。结果表明:只有组织因素中的安全管理和环境因素中的不安全环境是煤矿事故致因的必要条件;煤矿事故致因组态路径有8条;根据各组态路径中的核心条件归纳出的5种致因组态类型为安全监察主导型、安全管理主导型、组织管理综合型、组织环境联合型和安全认知缺失型。 展开更多
关键词 扎根理论 煤矿事故致因模型 TOE框架 安全管理 安全生产 组态路径
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张勉之教授基于补肾活血法论治尿酸性肾病
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作者 王婧 张勉之 《世界中西医结合杂志》 2024年第6期1122-1125,1138,共5页
尿酸升高是肾功能异常的独立危险因素,肾脏损伤也会导致患者尿酸排泄异常。尿酸性肾病的病因病机以禀赋素薄,脾肾亏虚为病理基础,饮食不节,湿瘀侵袭为发病机制。张勉之教授在以国医大师张大宁教授创立的补肾活血法为根本治疗大法的前提... 尿酸升高是肾功能异常的独立危险因素,肾脏损伤也会导致患者尿酸排泄异常。尿酸性肾病的病因病机以禀赋素薄,脾肾亏虚为病理基础,饮食不节,湿瘀侵袭为发病机制。张勉之教授在以国医大师张大宁教授创立的补肾活血法为根本治疗大法的前提下,依据潜伏期、发作期、缓解期体现出的不同证型辨证施治,疗效满意。 展开更多
关键词 尿酸性肾病 中医药 补肾活血法 辨证论治
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土茯苓等中药抑制URAT1表达及降尿酸作用筛选研究 被引量:72
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作者 孙红 王少明 +2 位作者 庄捷 黄旭慧 姚锦州 《中国临床药理学与治疗学》 CAS CSCD 2012年第4期403-407,共5页
目的:探讨中药制剂土茯苓、泽泻以及车前子是否调节高尿酸大鼠肾脏尿酸转运蛋白-1(uricacid transporters1,URAT1)mRNA表达。方法:将48只雄性Wistar大鼠随机分为正常对照组、模型组、苯溴马隆组、土茯苓组、泽泻组以及车前子组,每组8只... 目的:探讨中药制剂土茯苓、泽泻以及车前子是否调节高尿酸大鼠肾脏尿酸转运蛋白-1(uricacid transporters1,URAT1)mRNA表达。方法:将48只雄性Wistar大鼠随机分为正常对照组、模型组、苯溴马隆组、土茯苓组、泽泻组以及车前子组,每组8只。用氧嗪酸钾盐建立高尿酸血症大鼠模型。采用实时荧光定量PCR检测土茯苓、泽泻以及车前子对高尿酸大鼠肾脏URAT1基因的mRNA相对表达量。结果:苯溴马隆组、泽泻组、车前子组以及土茯苓组血尿酸值明显低于模型组(均P<0.01)。土茯苓、车前子与苯溴马隆组的URAT1mRNA表达均低于模型组。结论:土茯苓、车前子促进尿酸排泄机制可能与通过下调大鼠肾脏URAT1基因的mRNA表达有关。 展开更多
关键词 土茯苓 车前子 尿酸 urat1 基因表达
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玉米须总黄酮抗大鼠高尿酸血症及肾脏保护作用
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作者 黄宇涵 徐莎 +4 位作者 房伟 宋玮 贺雅静 张玉霞 马振勇 《郑州大学学报(医学版)》 CAS 北大核心 2024年第1期45-50,共6页
目的:探讨玉米须总黄酮(TFCS)抗大鼠高尿酸血症(HUA)及肾脏保护的价值。方法:将60只SD大鼠随机分成正常对照组,模型组,别嘌呤醇组和TFCS低、中、高剂量组,每组10只。除正常对照组外,其余各组给予250 mg/(kg·d)乙胺丁醇和100 mg/(kg... 目的:探讨玉米须总黄酮(TFCS)抗大鼠高尿酸血症(HUA)及肾脏保护的价值。方法:将60只SD大鼠随机分成正常对照组,模型组,别嘌呤醇组和TFCS低、中、高剂量组,每组10只。除正常对照组外,其余各组给予250 mg/(kg·d)乙胺丁醇和100 mg/(kg·d)腺嘌呤的混悬液灌胃14 d,构建大鼠HUA模型。造模后别嘌呤醇组给予50 mg/(kg·d)别嘌呤醇,TFCS低、中、高剂量组分别给予0.5、1.0、2.0 mg/(kg·d)TFCS灌胃14 d。观察并记录大鼠的一般状态和体重;检测大鼠血清中尿酸(UA)、肌酐(Cr)、尿素氮(BUN)、黄嘌呤氧化酶(XOD)水平及尿液中UA水平;HE染色观察肾组织病理形态变化;免疫组化法检测大鼠肾组织尿酸转运体1(URAT1)蛋白的表达;qRT-PCR法检测大鼠肾组织葡萄糖转运体9(GLUT9)mRNA的表达。结果:与正常对照组比较,模型组大鼠精神状态萎靡、排尿增多;血清UA、Cr、BUN、XOD水平升高,尿液UA水平降低(P<0.05);肾小管上皮边界模糊,细胞肿胀变性,肾间质炎性细胞浸润;肾组织URAT1蛋白和GLUT9 mRNA表达水平升高(P<0.05)。与模型组比较,别嘌呤醇组和TFCS低、中、高剂量组大鼠精神状态及排尿情况好转;血清UA、Cr、BUN、XOD水平降低,尿液UA水平升高(P<0.05);肾组织损伤减轻,URAT1蛋白和GLUT9 mRNA表达水平降低(P<0.05)。结论:TFCS可有效降低HUA大鼠UA水平,并对肾脏有一定保护作用,其作用机制可能与抑制UA合成关键酶活性及调节UA转运蛋白表达有关。 展开更多
关键词 玉米须总黄酮 高尿酸血症 大鼠 urat1 GLUT9
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