治疗糖尿病肾病的药物研究现状

随着人们生活水平的提高,人均寿命的延长,糖尿病及其慢性并发症对患者的健康和生命造成严重威胁,其中糖尿病肾病（DN ）是糖尿病主要的慢性并发症之一,是一种较为常见的疾病,也是导致终末期肾病（ESRD）的主要原因。目前中国已有9200万糖尿病患者,1．48亿糖尿病前期患者［1］。随着全球范围内糖尿病患者的不断增加,DN的患病率也随之提高。在西方国家DN是导致 ESRD的首要病因（约占35％）,在我国这一比例也在逐年上升［2］。D N 在1型糖尿病中患病率为33％～40％,在2型糖尿病中的患病率为20％～25％［3］。因此对DN的防治已经成为当前临床医生和医药研究人员共同面临的重要课题。研究已证实DN的发生和发展包括代谢紊乱、炎性反应、肾小球血流动力改变和遗传易感性等在内的多个方面共同作用的结果。现今医学界认为对DN防治的基本措施应包括有效控制血糖、控制血压、抑制肾素‐血管紧张素系统（RAS）和调脂治疗等,且临床已证实上述措施可有效降低蛋白尿水平和延缓DN的进展。近年来,DN的治疗取得了很大的进展,尤其在新药开发和药物配伍方面,这些进步极大地改善了DN患者临床症状和生活质量。本文现将近几年有关DN的药物治疗进展综述如下。     

PARP-1与氧化应激在糖尿病神经病变发病机制中的作用

糖尿病神经病变(diabetic neuropathy,DN)是糖尿病常见的并发症,患病率约为50%[1],其发病机制复杂,涉及激活众多通路神经生长因子[2]、炎性反应介质[3]及活性氧和氮等方面,现已成为糖尿病患者致残、致死的主要原因.     

中性粒细胞与淋巴细胞的比值在2型糖尿病肾病诊断中的初步应用

<正>炎症反应在糖尿病肾病(T2DN)的发病过程中的作用越来越受到人们的重视。中性粒细胞/淋巴细胞比值(neutrophil/lymphocyte ratio,NLR)是近年来提出的一个新的炎性反应指标~([1]),可反映机体炎性反应状态。研究发现,NLR较白细胞计数或淋巴细胞计数具有更高心血管疾病预测价值,且高水平NLR是远期病死率的独立危险因素,可作为心血管疾病的独立的预测指标~([2])。目前临床上主要根据临床症状、     

肠道微生物菌群与慢性肾脏病的研究进展

正肠道微生物群与宿主一直互利共存的,并在宿主的新陈代谢中扮演着重要角色。正常肠道微生物群以营养、代谢、生理和免疫功能等多方面影响着人体健康,而肠道微生物群菌群失调参与多种疾病的发生发展,如肥胖、2型糖尿病、炎症性肠病、心血管疾病等。目前越来越多的证据表明,肠道菌群失调参与了导致慢性肾脏病(chronic kidney disease,CKD)的进展以及并发症的发生,而补充益生菌可能对CKD患者具有潜在的收益,本文就肠道微生物菌群与CKD的关系,综述如下。1肠道微生物群     

维生素D延缓糖尿病肾病的研究进展

近年来,糖尿病肾病(diabetic nephropathy,DN)的发病率逐年上升,是导致终末期肾病的重要原因之一,目前尚无特效的防治手段来阻止其进展。研究发现维生素D(Vitamin D, VD)除调节钙磷代谢外,还具有抗炎、抗氧化、调节细胞凋亡、维持免疫、降低尿蛋白及改善胰岛素抵抗等作用。大量的动物实验和临床研究都证实,VD可能通过多种机制延缓DN发生、发展,为DN的治疗提供了新的思路。本文就VD在延缓DN进展中的作用予以综述。     

NF-κB在类风湿性关节炎中的作用及调控机制

正类风湿性关节炎(RA)是1种慢性、系统性自身免疫性疾病,可累及人体许多组织与器官,对关节的破坏尤为严重。主要病理特征为炎性细胞浸润、滑膜组织增生、血管生成、血管翳形成、软骨的破坏及骨的侵蚀。目前认为炎性反应介质的持续作用是RA病变加重的主要原因。NF-κB是1种影响广泛的转录因子,能促进多种基因转录和表达,与炎性反应、免疫应答     

胎盘生长因子在炎症性肠病血管生成和炎性反应中作用的研究进展

正胎盘生长因子(placental growth factor,PlGF)是一种分泌型的同源二聚体糖蛋白,是血管内皮生长因子(VEGF)家族中的一员。多项研究发现,PlGF在肿瘤和炎性疾病等的病理性血管生成中发挥重要的作用;而遗传学研究显示,内源性的PlGF对健康个体的血管生成和生理性血管维持不发挥作用。基于这些研究,血清PlGF不仅可以作为监测炎性反应和血管生成的一种有效标志物,还为肿瘤和炎性反应提供了新的治疗靶点。本文就PlGF的分子与生物学特点及其在肿瘤及炎性疾病,尤其是炎症性肠病血管生成和炎性反应中的作用作一综述。     

白细胞介素-18、胱抑素C在2型糖尿病肾病早期诊断的意义

糖尿病肾病（diabetic nephropathy,DN）是糖尿病（diabetes mellitus,DM）微血管病变的主要并发症之一[1],是DM的主要死亡原因。其发病机制十分复杂,越来越多的研究认为,糖尿病是一种自然免疫和低度炎性反应性疾病[2]。近年来,细胞粘附分子-18（interleukin-18,IL-l8）作为一种炎症因子,与糖尿病     

一氧化氮和内皮素在糖尿病肾病患者中的变化

一氧化氮（nitricoxide，NO）是近年来发现的一种舒张血管物质，具有多种生物学特性，内皮素（endothelin，ET）具有强烈收缩血管的活性。糖尿病肾病（DN）是2型糖尿病（DM）微血管并发症之一，其发生机理可能与内皮损伤及血小板功能异常有关，Trachtman等认为肾血流动力学紊乱可能是DN发生发展的直接原因，DN的确切发病机制及影响因素至今尚未完全阐明。     

一氧化氮和内皮素在糖尿病肾病患者中的变化

一氧化氮（nitricoxide，NO）是近年来发现的一种舒张血管物质，具有多种生物学特性，内皮素（endothelin，ET）具有强烈收缩血管的活性。糖尿病肾病（DN）是2型糖尿病（DM）微血管并发症之一，其发生机理可能与内皮损伤及血小板功能异常有关，Trachtman等认为肾血流动力学紊乱可能是DN发生发展的直接原因，DN的确切发病机制及影响因素至今尚未完全阐明。     

Isolation and gut microbiota modulation of antibiotic-resistant probiotics from human feces

Antibiotic-resistant probiotics may be advantageous for antibiotic-induced gut microbiota imbalance. In this article, we aimed to isolate antibiotic-resistant bacteria as potential probiotics. Feces from 3 healthy adults and 2 infants were used to isolate the antibiotic-resistant bacteria. Then we established gut microbiota imbalance mice model by antibiotics treatment and used it to assess the effect of the probiotics. Finally, we identified 8 isolates, and 6 of them were used as probiotics cocktail. Number of anaerobe, lactobacilli, and Bifidobacterium in feces were higher in the probiotic group (9.47 ± 0.35 log₁₀CFU/g, 8.74 ± 0.18 log₁₀CFU/g, 7.24 ± 0.38 log₁₀CFU/g, respectively) compared with model group (P < 0.05). Richness and diversity index of probiotic group (19.79 ± 0.29 and 2.95 ± 0.06, respectively) were larger than model group (P < 0.05). Diarrhea and mucosal edema had been alleviated during probiotic treatment. Our results validated that bacteriotherapy was available to treat gut microbiota imbalance.     

新生儿胆汁淤积性黄疸血清胆红素水平与肠道菌群失调的相关性

目的 探讨新生儿胆汁淤积性黄疸血清胆红素水平与肠道菌群失调的相关性。方法 选取2019年8月至2021年8月南阳市中心医院的新生儿胆汁淤积性黄疸患儿109例,同时选取母乳性黄疸患儿68例,健康新生儿80例。检测3组血清中胆红素水平和粪便标准肠道菌群,对比3组门水平优势菌群和属水平优势菌群的差异,采用Pearson相关系数分析血清胆红素水平与肠道菌群及肠道菌群失调的相关性。结果 胆汁淤积症组丙氨酸氨基转移酶(ALT)、直接胆红素水平和总胆红素比值(DBIL/TBIL)明显高于健康组和母乳性黄疸组(P均<0.05),胆汁淤积症组Ⅱ度菌群失调和Ⅲ度菌群失调占比明显高于健康组和母乳性黄疸组(P<0.05);胆汁淤积症组拟杆菌门和厚壁菌门水平显著高于母乳性黄疸组和健康组(P<0.05),胆汁淤积症组变形菌门水平显著低于母乳性黄疸组(P<0.05),胆汁淤积症组中放线菌门水平明显低于健康组和母乳性黄疸组(P均<0.05);胆汁淤积症组双歧杆菌和乳酸杆菌丰度显著低于健康组和母乳性黄疸组(P<0.05),胆汁淤积症组大肠杆菌和肠球菌丰度明显高于健康组和母乳性黄疸组(P<0.05),胆汁淤积症组双歧杆菌/大肠杆菌(B/E)值低于健康组和母乳性黄疸组(P<0.05);Pearson相关分析发现,ALT、TBIL、DBIL、DBIL/TBIL与拟杆菌门、厚壁菌门呈正相关(均P<0.05),与放线菌门呈负相关(均P<0.05);TBIL与双歧杆菌、B/E值呈负相关(均P<0.05),与大肠杆菌、肠球菌呈正相关(均P<0.05);DBIL与双歧杆菌、B/E值呈负相关(均P<0.05);DBIL/TBIL与双歧杆菌、大肠杆菌、肠球菌、B/E值呈负相关(均P<0.05)。结论 胆汁淤积性黄疸患儿菌群失调,双歧杆菌明显减少,且血清胆红素水平与菌群具有一定的相关性,积极补充益生菌可能成为治疗胆汁淤积性黄疸一种有效方式。     

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota

Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever‐increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota‐metabolized HMs, direct microbial analysis of HM‐targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM‐based drug discovery.     

肺-肠轴：儿童呼吸道感染与肠道微生态的相关性

肠道菌群是作为维持器官微环境的重要调节剂,由肠道-重要器官轴发挥作用。多项研究表明,肠道菌群及其代谢产物可有效预防和治疗呼吸系统疾病。然而,由于儿童肠道菌群的组成与成年人不同,并且其免疫系统正处于发育过程中,因此关于儿童肠道菌群与呼吸道感染之间相互作用的研究仍然很少。该文从“肺-肠轴”角度介绍了呼吸道感染儿童肠道菌群的变化,并分析了儿童肠道菌群与免疫功能和呼吸道感染之间的相关性,期望能为临床从肠道菌群入手治疗儿童呼吸道感染提供参考。     

Role of in vitamin D in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder affecting 10%-22% of adults. Its development is closely related to the gut microbiota, and the inflammatory and immune responses triggered by the gut microbiota can lead to IBS. Vitamin D (VD) effectively treats IBS with fewer side effects by improving gut microbiota, immune regulation, and anti-inflammatory effects. In the future, it is necessary to carry out epidemiological studies on the relationship between VD and IBS, clinical studies on the efficacy of supplementing VD to improve IBS, and animal studies on the mechanism of VD improving IBS. Therefore, this paper discussed the relationship between VD and IBS.     

The honey bee gut microbiota: strategies for study and characterization

Gut microbiota research is an emerging field that improves our understanding of the ecological and functional dynamics of gut environments. The honey bee gut microbiota is a highly rewarding community to study, as honey bees are critical pollinators of many crops for human consumption and produce valuable commodities such as honey and wax. Most significantly, unique characteristics of the Apis mellifera gut habitat make it a valuable model system. This review discusses methods and pipelines used in the study of the gut microbiota of Ap. mellifera and closely related species for four main purposes: identifying microbiota taxonomy, characterizing microbiota genomes (microbiome), characterizing microbiota–microbiota interactions and identifying functions of the microbial community in the gut. The purpose of this contribution is to increase understanding of honey bee gut microbiota, to facilitate bee microbiota and microbiome research in general and to aid design of future experiments in this growing field.     

Update on gut microbiota in gastrointestinal diseases

The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the “gut microbiota”. At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed “dysbiosis”, the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.     

Intestinal microecology-based treatment for inflammatory bowel disease: Progress and prospects

Inflammatory bowel disease (IBD) is a chronic, recurrent, and debilitating disorder, and includes Crohn’s disease and ulcerative colitis. The pathogenesis of IBD is closely associated with intestinal dysbiosis, but has not yet been fully clarified. Genetic and environmental factors can influence IBD patients’ gut microbiota and metabolism, disrupt intestinal barriers, and trigger abnormal immune responses. Studies have reported the alteration of gut microbiota and metabolites in IBD, providing the basis for potential therapeutic options. Intestinal microbiota-based treatments such as pre/probiotics, metabolite supplementation, and fecal microbiota transplantation have been extensively studied, but their clinical efficacy remains controversial. Repairing the intestinal barrier and promoting mucosal healing have also been proposed. We here review the current clinical trials on intestinal microecology and discuss the prospect of research and practice in this field.     

缺血性卒中与肠道菌群研究进展

缺血性卒中是最常见的脑血管病类型,是我国国民死亡的第一位原因。近年来的研究表明肠道菌群及其代谢产物在卒中相关危险因素如高血压、糖尿病、动脉粥样硬化等病理生理过程中有重要作用。肠道菌群可通过调节肠道白细胞介素（IL） 17+γδT细胞向脑膜区的迁移影响卒中结局。还有研究发现卒中相关性肺炎的细菌来源于肠道等。总之,目前相关研究表明肠道菌群影响卒中的发生发展。本文对肠道菌群与卒中相关危险因素、卒中事件及卒中相关并发症做一综述。     

Fecal transplantation for ulcerative colitis: current evidence and future applications

ABSTRACT

Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment for patients with recurrent Clostridium difficile infection and has been investigated also in patients with UC, with promising results.

Areas covered: Literature review was performed to select publications concerning current evidence on the role of gut microbiota in the pathogenesis of UC, and on the effectiveness of FMT in this disorder.

Expert opinion: The randomized controlled trials published investigating the use of FMT suggested a potential role for FMT in the treatment of mild to moderate UC. However, given several unanswered questions regarding donor selection, dose, route of administration and duration of therapy, this is not yet recommended as a viable therapy option. FMT has allowed for more in depth investigation with regards to the role the gut microbiota may be playing in UC. This knowledge is critical to identifying where FMT may appropriately fit in the UC treatment paradigm. As our understanding of the role the microbiome plays in this chronic disease, FMT, and then eventually defined microbes, will hopefully serve in a complementary role to conventional IBD therapies.