肠道菌群与高尿酸血症及痛风的相关性研究

高尿酸血症以及痛风的发病率持续升高,已经成为一个重大的公共卫生问题。肠道菌群的结构改变或失调可引起机体代谢紊乱,肠道微生态尤其与代谢性疾病的发生发展关系密切。目前研究发现高尿酸血症、痛风患者存在肠道菌群失调,降尿酸治疗后肠道菌群可发生相应改变,并且益生菌制剂具有降尿酸作用。本文概述高尿酸血症及痛风患者的肠道菌群特点,从高嘌呤及高果糖饮食对肠道菌群的影响、肠道参与嘌呤和尿酸的代谢、代谢性内毒素血症以及痛风相关炎症因子等方面探讨肠道菌群与高尿酸血症及痛风的关系,并展望肠道菌群可能成为未来诊治高尿酸血症以及痛风的一种新方法。     

基于肠道菌群防治高尿酸血症的研究进展

高尿酸血症是由嘌呤代谢异常引起尿酸生成过多和(或)排泄减少导致血尿酸超出正常范围的代谢性疾病.目前研究已证实,促进尿酸合成的酶在肠道中高表达,人体1/3的尿酸经肠道排泄.随着微生物学研究的快速发展,肠道菌群的研究也逐渐深入,发现高尿酸血症患者肠道菌群的结构和数量均发生变化,肠道菌群可能是高尿酸血症的肠道触发因素.肠道菌...     

痛风与肠道菌群相关性的研究进展

痛风是一种嘌呤代谢紊乱导致的炎症性疾病,表现为尿酸升高、阵发性关节肿痛、痛风结石形成和关节畸形等,严重影响患者的工作及生活质量。随着生活方式的改变,痛风的患病率不断升高。嘌呤代谢障碍和炎症通路异常在痛风的发病机制中起主要作用。研究表明痛风会引起肠道菌群的改变,肠道菌群不仅能够影响嘌呤代谢或调节炎症,还能够影响药物对痛风的治疗效果。因此本综述从肠道菌群调节嘌呤代谢、炎症反应及药物作用等方面,分析肠道菌群在痛风发病及治疗中的作用及功能,有助于阐明痛风与肠道菌群的相关性,为更好地诊治痛风提供新思路。

     

肠道菌群失调与高尿酸血症关系的研究进展

高尿酸血症（hyperuricemia,HUA）是一种涉及肝、肾、肠等多个器官的代谢性疾病,因尿酸代谢异常而引起代谢障碍。尿酸在肝脏和肾脏中的代谢途径目前已经被阐明,但在肠道内的代谢途径尚未完全清晰。肠道菌群在人体肠道中定植,与宿主存在互惠共生的关系,在宿主的代谢和免疫调节中起着至关重要的作用。肠道菌群结构的变化可能引起代谢紊乱,肠道菌群参与嘌呤代谢酶的合成和炎症因子的释放,与HUA的发生发展密切相关。肠道菌群作为探讨HUA发病机制的切入点,已成为新的研究热点。本综述主要阐述HUA与肠道菌群之间的关系,探讨肠道菌群抗HUA的机制,如肠道菌群促进嘌呤和尿酸分解代谢,影响尿酸排泄,以及HUA引起的肠道炎症反应等,以期为通过调节肠道菌群来治疗HUA提供一定的依据。

     

肾脏尿酸转运体的研究进展

尿酸是人体内嘌呤代谢的终产物。在肝脏合成后,正常情况下约70%的尿酸在肾脏分泌,而一小部分则被分泌到肠内。肾脏是血尿酸稳态调节的主要器官,其调控依赖于尿酸转运体的转运。尿酸代谢紊乱或转运异常将导致高尿酸血症、痛风、痛风性肾结石等疾病。本文对肾脏尿酸转运体的研究进展进行综述。     

高尿酸血症与高血压病相关性的研究进展

尿酸是人体内嘌呤代谢的最终产物,当尿酸生成增多和/或排出减少时,均可引起血中尿酸盐浓度增高。当血尿酸水平男性大于7.0 mg/dl,女性大于6.0 mg/dl称为高尿酸血症。作为嘌呤代谢紊乱所致疾病,高尿酸血症以往仅侧重于痛风性关节炎、痛风石沉积和肾尿酸结石形成等的诊断与治疗。目前新近研究表明:高尿酸血症可能是高血压病的独立危险因素之一且尿酸水平增高通常早于高血压的发生与进展,干预尿酸水平有望成为高血压治疗的新靶点,随着高血压研究的全球化深入,对于尿酸及尿酸水平增高的流行病学、基础学与临床方面的研究也日益备受关注。基于此,本文对尿酸的合成与代谢;高尿酸血症成因及其与高血压的流行病学研究;高尿酸血症通过引发一氧化氮合成水平减低、血管平滑肌细胞生物学行为改变、机体炎症与氧化应激反应及肾素-血管紧张素系统激活等方面所致高血压的发病机制;高尿酸血症干预治疗对于高血压病的转归进行简要综述。     

血清尿酸对心血管系统及神经退行性病变的影响

尿酸是人体嘌呤代谢的最终产物。高尿酸血症,即血清尿酸水平过高,是引发痛风的主要病因。越来越多的流行病学研究将高尿酸血症与心血管系统疾病和神经退行性病变紧密联系在一起。这些研究表明,炎性反应极有可能是高尿酸水平引发痛风的致病机制。同时,炎性反应与尿酸引起的心血管系统改变息息相关。尿酸钠晶体被认为通过Toll样受体家族诱发炎症反应诱导炎症的发生。此外,可溶性尿酸可以促进自由基的生成,起到促进氧化的作用。本综述总结了近期关于高尿酸血症和心血管系统疾病的流行病学研究,简要回顾了高尿酸血症在神经退行性病变中的作用,并描述了尿酸诱导的炎症产生机制。     

微生物参与人体尿酸的合成、分解和转运

由于人类在进化过程中缺失了尿酸酶,因此尿酸成为人类嘌呤代谢的不溶性终产物,其生成过多或排泄减少,均可导致高尿酸血症和痛风。人体中70%的尿酸经肾脏排泄,其余的30%经肠道排泄。微生物与人体尿酸的合成、分解和转运息息相关。某些微生物在调控人体微生物组、降解食物中的嘌呤类物质、参与尿酸合成与分解及调控肾－肠轴的尿酸转运中起重要作用,有望为治疗高尿酸血症和痛风提供有别于使用传统化学药物和植物药物的新方法。本文主要就人体尿酸的合成、分解与转运机制及微生物在人体尿酸的合成、分解和转运中的作用作一综述。

     

肠道菌群与非编码RNA互作对疾病影响的研究进展

肠道菌群数量庞大,种类繁多,被认为是一个独立的器官系统,是人体生理和代谢稳态的重要组成部分,肠道菌群的稳态失调以及某些代谢产物的分泌已被证实可以参与人体多种疾病的发生发展。同样,非编码RNA（ncRNA)数量庞大,种类较多,主要包括微小RNA（miRNA)、长链RNA(lncRNA)、环状RNA(circRNA)。ncRNA早期因无蛋白质编码能力未引起重视,随着研究的深入,认识到了其对多种疾病都具有重要的调控作用,近些年获得了更多的关注。目前,多项研究揭示了肠道菌群-ncRNA互作对多种疾病的发生、发展、诊断、治疗等方面的影响,二者互作可能是未来疾病防治的重要突破口。本文就肠道菌群与ncRNA的互作对不同疾病的作用进行综述,以期为疾病的防治提供参考。     

microRNA 对宿主和肠道微生物互作的调控

摘要:肠道内环境是宿主和肠道微生物菌群互作的结果,肠道菌群一方面通过抗原物质调节肠道组织的免疫稳定,另一方面,肠道菌群参与糖、脂、蛋白质代谢,产生的代谢产物能够调控细菌营养代谢、群体结构和肠道组织的营养吸收等。microRNA是宿主细胞内调控基因表达的重要因子,肠道微生物菌群不仅调控宿主mRNA的转录,同时也影响某些基因的转录后修饰。研究表明,肠道菌群通过与宿主肠道组织互作,调节肠上皮组织内某些参与炎症应答和屏障功能的microRNA 的表达。本文介绍了肠道微生物与宿主互作的基本内容,对microRNA在肠道微生物与宿主互作和肠道健康中的调节进行综述。     

Comorbidities in patients with gout

Gout is one of the most important diseases associated with hyperuricemia. Gout is characterized by acute monoarthritis with frequent flares. Some patients with gout have gouty tophi that are composed of monosodium urate crystals and inflammatory cells. In addition to tophi, gout is associated with various comorbidities such as obesity, hypertension, abnormal lipid metabolism, renal dysfunction, and urolithiasis. We examined the associations of the presence of tophi and comorbidities with demographic and disease characteristic data of gout patients. Subjects were 422 male patients with gout who visited our outpatient clinic. The patients' background data and laboratory data at the first visit were collected from patient records. We investigated the relationship between comorbidities and characteristics of patients using multiple regression models. The age of gout onset was 44 ± 13 years. The duration of gout at the first visit was 6 ± 8 years. Five percent of subjects had tophi. The presence of tophi was significantly associated with the duration of gout and maximum serum uric acid (SUA), indicating a close association of tophi with urate deposition. Reduced estimated glomerular filtration rate was associated with older age of onset, longer duration of gout, and higher levels of maximum SUA, indicating that sustained hyperuricemia relates with renal impairment of gout. Urolithiasis did not associate with gout duration and maximum SUA. The increased frequency of hypertension was associated with the duration of gout, suggesting that poor control of gout is one of the causes of hypertension. This study provides useful information for gout management and patient education.     

Development of novel NLRP3-XOD dual inhibitors for the treatment of gout

Gout is a crystalline-related arthropathy caused by the deposition of monosodium urate (MSU). Acute gouty arthritis is the most common first symptom of gout. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome as pattern recognition receptors can be activated by uric acid crystallization, triggering immune inflammation and causing acute gouty arthritis symptoms. Currently, the treatment of gout mainly includes two basic methods: reducing uric acid and alleviating inflammation. In this paper, 22 novel benzoxazole and benzimidazole derivatives were synthesized from deoxybenzoin oxime derivatives. These compounds have good inhibitory effects on NLRP3 and XOD screened by our research group in the early stage. The inhibitory activities of XOD and NLRP3 and their derivatives were also screened. Notably, compound 9b is a multi-targeting inhibitor of NLRP3 and XOD with excellent potency in treating hyperuricemia and acute gouty arthritis.     

Focus: Rare Disease: A Case of Spinal Infectious Osteomyelitis Versus Gout: Advanced Imaging with Dual Energy CT

A 67-year-old male presented to the hospital for lower back pain and left lower extremity radiculopathy. Although the patient was afebrile and white blood cell count was normal, MRI was concerning for discitis/osteomyelitis at L4-L5. Subsequently, the patient developed a right knee joint effusion and underwent an arthrocentesis that was notable for the presence of urate crystals. A systemic urate crystal arthropathy was proposed as a potential etiology for the patient’s back pain and radiculopathy. Dual energy CT of the lumbar spine was performed, a technique which determines material composition by comparing the photon attenuation of the substance from two different x-ray energy levels. Results revealed the presence of monosodium urate crystals in the intervertebral discs. This technique is proposed as a noninvasive way to evaluate for gout in atypical locations or those difficult to sample and may replace an invasive intervertebral disc/endplate aspiration and/or biopsy. Dual energy CT should be considered in patients with elevated serum uric acid and concern for spinal involvement of gout.     

双歧杆菌四联活菌联合常规用药治疗痛风的效果

探究双歧杆菌四联活菌联合常规用药治疗痛风的效果,为该类患者的治疗提供参考。

选取2018年12月至2020年12月我院300例痛风患者作为研究对象进行前瞻性研究,按照随机数字表法按1∶1比例分为联合组和常规组,各150例。常规组患者采用常规治疗,联合组在常规组基础上加用双歧杆菌四联活菌。比较2组患者疗效,治疗前后血尿酸、粪便中尿酸、粪便中细菌分解的尿酸、肠道菌群（双歧杆菌、乳杆菌、拟杆菌、大肠埃希菌）、炎症因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、环氧化酶-2（COX-2）、白细胞介素-6（IL-6）]水平、血管内皮功能[可溶性细胞间黏附分子-1（sICAM-1）、一氧化氮（NO）、内皮素-1（ET-1）]及不良反应发生率。

联合组患者总有效率（91.33%）高于常规组（83.33%）,差异有统计学意义（P＜0.05）。治疗后联合组患者血尿酸、粪便中尿酸水平低于常规组,粪便中细菌分解的尿酸水平高于常规组（均P＜0.05）。治疗后联合组患者肠道双歧杆菌、乳杆菌数量高于常规组,拟杆菌、大肠埃希菌数量低于常规组（均P＜0.05）。治疗后联合组患者血清IL-1β、TNF-α、COX-2、IL-6、sICAM-1、ET-1水平低于常规组,而NO水平高于常规组（均P＜0.05）。2组患者不良反应发生率差异无统计学意义（P＞0.05）。

双歧杆菌四联活菌辅助治疗痛风的效果显著,可有效降低尿酸水平,调节肠道菌群稳定,缓解机体炎症,改善血管内皮功能,安全性较高。

     

Fine needle aspiration of tophi for crystal identification in problematic cases of gout. A report of two cases

BACKGROUND: The definitive diagnosis of gout is best established by demonstration of monosodium urate (MSU) crystals in the synovial fluid or biopsy. Fine needle aspiration cytology (FNAC) of tophi can play a crucial role in diagnosis. CASES: A 36-year-old chronic alcoholic male developed subcutaneous nodules on both malleoli without a history of arthropathy and with normal serum uric acid levels. FNAC of the nodules demonstrated stacks and sheaves of needle-shaped crystals of MSU. A 50-year-old diabetic male developed multiple nodules on the feet. He gave a past history of painful athropathy. A roentgenogram of the feet was suspicious for gout; however, joint aspiration failed, and the serum uric acid levels were normal. At this juncture FNAC of the feet tophi clinched the diagnosis of gout. In both cases, polarization of needle washings (wet mount) and the fixed, Papanicolaoustained smears showed negatively birefringent, needle-shaped crystals of MSU, thus confirming the diagnosis of gout. CONCLUSION: FNAC of gouty tophi is an easy alternative to synovial biopsy and joint fluid analysis. It is simpler, easier and less painful. As crystals are preserved in stained smears, they can be employed for polarization and confirmation of gout.     

齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响

采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。