染料木素、芹菜素、槲皮素、芦丁和落新妇苷对高尿酸血症小鼠黄嘌呤氧化酶活性及血清尿酸水平的影响

目的探讨黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性的影响,对高尿酸血症小鼠血清和肝脏黄嘌呤氧化酶活性的影响,同时评价对小鼠血清尿酸水平的作用。方法采用改良的紫外分光光度法测定染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶的抑制作用;采用尿酸酶抑制剂氧嗪酸钾诱导小鼠高尿酸血症模型,以分光光度法研究对小鼠血清和肝脏黄嘌呤氧化酶活性的影响,以磷钨酸法测定对小鼠血清尿酸水平的作用。结果体外实验表明这些黄酮类化合物对黄嘌呤氧化酶活性无明显影响。然而,体内实验观察到能够明显升高或降低黄嘌呤氧化酶的活性,而且,血清尿酸水平与血清黄嘌呤氧化酶活性密切相关,与肝脏黄嘌呤氧化酶活性无明显关联。该研究表明用这些黄酮类化合物给药的小鼠血清尿酸水平都高于正常对照组。结论这5种黄酮类化合物不能够作为替代别嘌醇的药物用来降低血清尿酸水平。     

中药活性成分降尿酸作用机制研究进展

高尿酸血症是由嘌呤类物质代谢紊乱和(或)尿酸排泄减少引起血尿酸增高的一组异质性疾病。中药治疗高尿酸血症的研究逐步受到关注,并取得明显进展。近年来大量实验研究表明,黄酮、皂苷、生物碱等多种中药活性成分通过抑制腺苷脱氨酶和(或)黄嘌呤氧化酶的活性减少尿酸生成,或通过调控尿酸转运蛋白的表达增加尿酸排泄,从而发挥降尿酸的药理作用。该文以高尿酸血症的发病机制为基础,对中药活性成分降尿酸的作用机制研究进行总结,综述近年的研究报道。     

中国南海海绵提取物-renierol抗痛风作用的实验研究

目的探讨中国南海海绵提取物renierol对黄嘌呤氧化酶的抑制作用及对小鼠高尿酸血症的影响和可能的作用机理。方法从海绵中分离提取renierol成分,采用尿酸生成法和超氧离子致NBT显色法测定黄嘌呤氧化酶活性,并进一步研究其作用机理。结果两种实验显示其对黄嘌呤氧化酶有明显的抑制作用,IC50分别为1.85和1.36μg.mL-1。结论该海绵中renierol成分能有效抑制黄嘌呤氧化酶。     

以黄嘌呤氧化酶为靶点的新型非嘌呤类抗痛风及高尿酸血症药物研究进展

黄嘌呤氧化酶（XO）催化黄嘌呤生成尿酸及次黄嘌呤生成黄嘌呤的过程,是抗高尿酸血症或痛风药物研究的关键靶点。黄嘌呤氧化酶抑制剂由于作用机制明确、疗效显著而倍受关注,研发新型XO抑制剂具有广阔的应用前景。XO的结构生物学及分子模拟技术为新一代非嘌呤类XO抑制剂的合理药物设计奠定了基础。本文综述了以黄嘌呤氧化酶为靶标的新型非嘌呤类小分子杂环化合物及天然产物来源的活性分子在抗高尿酸血症或痛风药物研究领域中的进展。     

金线莲提取物对黄嘌呤氧化酶活性及高尿酸血症小鼠的影响

目的 研究金线莲提取物体外抑制黄嘌呤氧化酶活性的作用和体内降尿酸的作用.方法 用黄嘌呤氧化酶(XOD)试剂盒测定不同浓度金线莲乙醇提取物和水提取物对黄嘌呤氧化酶活性的抑制作用;采用小鼠高尿酸血症模型研究了金线莲水提物对尿酸和肌酐水平的影响.结果 金线莲水提物对黄嘌呤氧化酶(XOD)具有较强的抑制作用,金线莲水提物低、高剂量组均显著降低血清尿酸水平(P<0.01)和血清肌酐水平(WTBXP<0.01).结论 金线莲水提物对小鼠高尿酸血症模型具有一定的治疗作用.     

抗痛风用药14问

1常用于治疗痛风的西药有哪些? 常用于治疗痛风的西约有:(1)别嘌呤醇.它能抑制黄嘌呤氧化酶,减少尿酸的生成而有抗痛风作用;可防止肾中形成尿酸结石.用于痛风及高尿酸血症、尿酸性肾病.     

具有黄嘌呤氧化酶抑制作用的天然产物之研究进展

黄嘌呤氧化酶(xanthine oxidase,XOD)参与体内嘌呤的代谢,是尿酸(uric acid,UA)生成的关键酶,成为临床治疗高尿酸血症的重要靶点.抑制XOD对治疗痛风等高尿酸血症相关的疾病以及组织氧化损伤具有重要作用.本文对具有XOD抑制作用的天然产物的研究进展进行综述.     

染料木素等5种黄酮类物质对小鼠血清尿酸水平及黄嘌呤氧化酶活性的影响

目的探讨黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性的影响,对正常小鼠血清和肝脏黄嘌呤氧化酶活性的影响,同时评价对小鼠血清尿酸水平的作用。方法采用改良的紫外分光光度法测定染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶的抑制作用,采用分光光度法研究对小鼠血清和肝脏黄嘌呤氧化酶活性的影响,以磷钨酸法测定对小鼠血清尿酸水平的作用。结果体外实验表明黄酮类化合物染料木素、芹菜素、槲皮素、芦丁和落新妇苷体外对黄嘌呤氧化酶活性无明显影响。体内实验观察到这5种黄酮类化合物能够显著升高或降低黄嘌呤氧化酶的活性;而且,血清尿酸水平与血清黄嘌呤氧化酶活性密切相关,与肝脏黄嘌呤氧化酶活性无明显关联。用这些黄酮类化合物给药的小鼠血清尿酸水平都高于正常对照组。结论这5种黄酮类化合物不能够作为替代别嘌醇的药物用来降低血清尿酸水平。     

药品不良反应信息通报警惕别嘌醇片引起的重症药疹

别嘌醇为次黄嘌呤的异构体,是黄嘌呤氧化酶（XO）的抑制剂,可阻止次黄嘌呤和黄嘌呤代谢为尿酸,从而减少尿酸的生成,是目前唯一能抑制尿酸合成的药物。临床主要用于：①原发性和继发性高尿酸血症,尤其是尿酸生成过多而引起的高尿酸血症;②反复发作或慢性痛风者;③痛风石;④尿酸性肾结石和（或）尿酸性肾病;⑤有肾功能不全的高尿酸血症。剂型为片剂。     

桑抹茶对高尿酸血症模型大鼠血尿酸水平及肠道菌群的影响

目的 观察桑抹茶对高尿酸血症模型大鼠血清尿酸及肠道菌群的调节作用。方法 采用高嘌呤饲料喂养复制高尿酸血症大鼠模型,同时给予桑抹茶干预,于实验期末,用全自动生化仪检测血清尿酸、肌酐、尿素氮水平,ELISA法检测血清及肝组织黄嘌呤氧化酶活性和细菌内毒素水平;收集粪便,提取肠道菌群DNA,进行16S rRNA生物信息学分析。结果 桑抹茶干预能显著降低模型大鼠血清尿酸、肌酐、尿素氮水平及血清、肝组织黄嘌呤氧化酶活性;增加肠道乳杆菌比例,降低血清内毒素水平。RAD结果显示,肠道菌群分类水平与血尿酸、黄嘌呤氧化酶活性相关。结论 桑抹茶具有降尿酸作用,该作用可能与调节肠道菌群,降低血清内毒素水平,抑制黄嘌呤氧化酶活性有关。     

土茯苓水提物对高尿酸血症模型小鼠血清尿酸和甘油三酯、胆固醇的影响

目的:研究土茯苓水提物对高尿酸血症模型小鼠血清尿酸(UA)和甘油三酯(TG)、胆固醇的影响。方法:实验分为空白(等容蒸馏水)、模型(等容蒸馏水)、土茯苓水提物(10g(生药)·kg-1)、别嘌呤醇(40mg·kg-1)组。ig酵母30g·kg-11周复制模型,复制模型成功后分别ig相应药物,7d后检测各组大鼠血中胆固醇、TG、UA含量和黄嘌呤氧化酶(XOD)活性。结果:与模型组比较,土茯苓组小鼠血清UA、TG、胆固醇含量和XOD显著降低(P>0.05或P<0.01)。结论:土茯苓对高尿酸血症模型小鼠肾功能有保护作用,对UA升高有明显的抑制作用。     

南极磷虾肽改善高尿酸血症机制研究

目的 探究南极磷虾肽(AKP)对于高尿酸血症模型小鼠的降尿酸功效及其作用机制.方法 采用高效液相色谱(HPLC)法体外筛选出具尿酸合成关键限速酶—黄嘌呤氧化酶(Xanthine oxidase,XOD)抑制活性的AKP,体内动物实验验证AKP的降尿酸活性.雄性Balb/c小鼠采用高嘌呤饲料(25％酵母浸粉)喂养联合腹腔...     

Combined anti-hyperuricemia effect of Di.E and Gpm.E on hyperuricemia rats induced by high-purine diet

OBJECTIVE Di.E and Gpm.E were separately extracted from two kinds of traditional Chinese medicine.The aim of this research is to investigate the combined anti-hyperuricemia effect of Di.E and Gpm.E on hyperuricemia rats induced by high-purine diet,and to study the underlying mechanism.METHODS Sprague Dawley(SD)rats were divided into some groups according to their serum uric acid(UA),the normal control group received standard diet,while others were fed with high-purine diet.After the success of modeling,SD rats were divided into 5groups according to UA:normal control group,model control group,Di.E and Gpm.E(high,middle,low dosages).The treatment groups were simultaneously orally administered.Two days before the last administration,the urine N-acetyl beta-D Glucosaminidase(NAG),Lysozyme(LYS)activity were separately detected using the urine collected from metabolic cage for 24 h.After the last administration,the blood was taken from postcava to detect the level:① The related indexes of liver and kidney function:the serum UA,blood urea nitrogen(BUN),creatinine(CR),alanine aminotransferase(ALT);② The uric acid metabolism related enzymes:the serum and liver xanthine oxidase(XOD),adenosine deaminase(ADA),guanine deaminase(GD),xanthine dehydrogenase(XDH)activity;③ Fibrosis related indexes of renal tissue:connective tissue growth factor(CTGF),monocyte chemotactic protein-1(MCP-1),TGF-β1,TNF-α,NF-κB levels.RESULTS Di.E and Gpm.E(high,middle dosages)could markedly reduce the serum UA level significantly,also can decrease XOD,ADA,TNF-α,MCP-1,NF-κB activity significantly.CONCLUSION The results show that Di.E and Gpm.E can decrease the serum UA level significantly,improve the liver and kidney function and slow down the process of renal fibrosis;the therapeutic effects may be related to their inhibition of XOD,ADA activity.     

Evaluating the urate-lowering effects of different microbial fermented extracts in hyperuricemic models accompanied with a safety study

Uric acid (UA) is an end product of purine metabolism by the enzyme xanthine oxidase (XOD). Hyperuricemia is characterized by the accumulation of serum UA and is an important risk factor for gout and many chronic disorders. XOD inhibitors or uricase (catalyzes UA to the more soluble end product) can prevent these chronic diseases. However, currently available hypouricemic agents induce severe side effects. Therefore, we developed new microbial fermented extracts (MFEs) with substantial XOD inhibition activity from Lactobacillus (MFE-21) and Acetobacter (MFE-25), and MFE-120 with high uricase activity from Aspergillus. The urate-lowering effects and safety of these MFEs were evaluated. Our results showed that MFE-25 exerts superior urate-lowering effects in the therapeutic model. In the preventive model, both MFE-120 and MFE-25 significantly reduced UA. The results of the safety study showed that no organ toxicity and no treatment-related adverse effects were observed in mice treated with high doses of MFEs. Taken together, the results showed the effectiveness of MFEs in reducing hyperuricemia without systemic toxicity in mice at high doses, suggesting that they are safe for use in the treatment and prevention of hyperuricemia.     

摄食海参皂苷对小鼠高尿酸血症的影响

目的研究海参皂苷对酵母浸粉诱导的高尿酸血症小鼠的尿酸代谢及相关酶活性的影响。方法将24只♂昆明种小鼠随机分为正常组、模型组、皂苷低、高剂量组。采用口服酵母浸粉进行造模,连续喂饲14 d,分别测定小鼠血清尿酸(uric acid,UA)、肌酐(creatinine,Cr)、尿素氮(blood ureanitrogen,BUN)水平,以及肝脏黄嘌呤氧化酶(xanthine oxi-dase,XOD)、腺苷脱氨酶(adenosine deaminase,ADA)活性。结果喂养14 d后,海参皂苷高、低剂量组血清尿酸水平分别较对照组降低53.1%与55.6%(均P<0.01),肝脏XOD及ADA的活性明显受到抑制,XOD活性分别降低26.3%与28.6%(均P<0.01),ADA活性分别降低24.4%(P<0.05)与34.0%(P<0.01),血清肌酐与尿素氮无变化。结论海参皂苷对酵母浸粉诱导的高尿酸血症有明显的改善作用,其机制与抑制了肝脏XOD和ADA活性有关。     

松叶提取物对“过食膏粱厚味”型高尿酸血症大鼠尿酸生成排泄、肝功能及血脂水平的影响

目的 研究松叶提取物对“过食膏粱厚味”型高尿酸血症大鼠尿酸生成排泄、肝功能及血脂水平的影响。方法 将60只♂SD大鼠,随机分为正常对照组、模型对照组、别嘌醇（0.01 g·kg^-1）阳性对照组、松叶提取物3个剂量组（10.0,5.0,2.5 g·kg^-1）,每组10只。除正常对照组给予等体积蒸馏水,其余各组每天上午灌胃给予脂肪乳剂造模,下午灌胃给药,连续9周。观察大鼠一般行为学、摄食量、体质量,分别检测大鼠血清SUA、SCR、BUN、ALT、AST、TC、LDL-c含量;收集24 h尿液,记录UV,检测大鼠尿UUA、UCR含量,计算24 h UUA、FEUA、CUr、CCr,末次给药后测定血清和肝脏XOD、ADA、HGPRT活性。结果 模型对照组大鼠体质量明显降低,血清SUA、SCR、BUN、ALT、TC、LDL-c水平以及血清和肝组织XOD、ADA活性显著升高,肝组织HGPRT活性显著降低,同时UUA、UCR、UV、24 h UUA、FEUA、CUr、CCr显著降低。松叶提取物能显著降低高尿酸血症大鼠血清SUA、SCR、BUN、ALT、TC、LDL-c水平,降低血清和肝组织XOD、ADA活性,升高肝组织HGPRT活性,并且升高UUA、UCR、UV、24 h UUA、FEUA、CUr、CCr。结论 松叶提取物能有效降低HUA大鼠尿酸的生成并促进其排泄,且具有保肝、调血脂的功能。     

土茯苓对高尿酸症小鼠血清尿酸的影响

目的 观察土茯苓对高尿酸症小鼠的血清尿酸的影响.方法 将昆明种小鼠分为空白组,模型组,土茯苓低、中、高剂量治疗组,别嘌呤醇治疗组,造模成功后分别给予土茯苓、别嘌呤醇灌胃,7d后检测各组大鼠血中尿酸(UA)及黄嘌呤氧化酶(XOD).结果 治疗7d后,与模型组相比,土茯苓各剂量治疗组大鼠血中尿酸、黄嘌呤氧化酶明显降低(P＞0.05).结论 土茯苓对高尿酸症小鼠尿酸有明显的治疗作用.     

Hypouricemic action of selected flavonoids in mice: structure-activity relationships

Hyperuricemia and gout appear to be rapidly increasing worldwide and frequently cause symptoms of metabolic syndrome. Dietary flavonoids have their potential beneficial effects on human health. In the present study, 15 flavonoids (quercetin, morin, myricetin, kaempferol, icariin, apigenin, luteolin, baicalin, silibinin, naringenin, formonoetin, genistein, puerarin, daidzin and naringin dihydrochalcone) were selected to investigate for their hypouricemic action in mice. Oral administration of quercetin, morin, myricetin, kaempferol, apigenin and puerarin at 50 and 100 mg/kg for 3 d was able to elicit hypouricemic actions in hyperuricemic mice induced by potassium oxonate. Luteolin, formonoetin and naringenin showed the significant effects only at 100 mg/kg. Quercetin, puerarin, myricetin, morin and kaempferol significantly reduced liver uric acid level in hyperuricemic animals. In addition, quercetin, morin, myricetin, kaempferol and puerarin exhibited significant inhibition on the liver xanthine oxidase (XOD) activities. It seems to be likely that these flavonoids reduce serum urate levels by mainly inhibiting XOD activity. However, the hypouricemic effect of apigenin observed seemed not to parallel with the changes in liver uric acid level and liver XOD activity, implying that apigenin might act via other mechanisms apart from inhibiting enzyme activity simply. Analysis of the chemical structure showed that a planar structure with the hydroxyl groups played a crucial role in hypouricemic activity of flavonoids. The exact mechanism of the hypouricemic action of flavonoids in vivo should be investigated in the future.     

基于TMT蛋白组学探讨迷迭香酸抗大鼠高尿酸血症的作用机制

目的 结合TMT蛋白组学技术,探讨迷迭香酸抗大鼠高尿酸血症的作用机制。方法 将SD大鼠随机分为对照组、模型组、苯溴马隆组、迷迭香酸（50、100 mg/kg）组,除对照组给予蒸馏水外,其他各组大鼠均饮用10%果糖水建立高尿酸血症模型。连续给药4周后,检测血清尿酸水平,黄嘌呤氧化酶（XOD）与腺苷脱氨酶水平（ADA）活性,苏木素–伊红（HE）染色观察回肠组织病理变化,实时荧光定量PCR法（RT-qPCR）检测回肠组织尿酸转运体三磷酸腺苷结合转运蛋白G2（ABCG2）、葡萄糖转运体9（GLUT9）mRNA的表达,TMT蛋白组学检测大鼠回肠组织蛋白的表达。结果 与模型组比较,迷迭香酸可显著降低大鼠血清尿酸水平,降低XOD与ADA活性（P＜0.05、0.01、0.001）,以及回肠组织内的GLUT9 mRNA的表达（P＜0.05）。TMT蛋白组测序共筛选出2 975个差异蛋白（log₂FC＞1.5,P＜0.05）,通路分析显示迷迭香酸主要调节Th1/2/17细胞分化等通路。结论 迷迭香酸发挥抗大鼠高尿酸血症的作用机制可能与抑制ADA和XOD的活性,调节肠道GLUT9 mRNA表达和Th1/2/17细胞分化通路有关。