天然黄酮类化合物防治糖尿病肾病的研究进展

糖尿病肾病（DN）是一种严重的糖尿病并发症,其发病机制复杂而多样。现代药理研究表明,天然黄酮类化合物具有多种潜在药用价值,对糖尿病肾病的防治作用就是其中之一。黄酮类化合物抗糖尿病肾病的作用机制是多方面药理活性的综合结果,包括通过抗氧化应激与清除自由基、抗炎、改善血糖血脂紊乱、抗凋亡、调节血管舒张及改善血流动力学异常等途径来实现。在查阅近年来国内外发表的相关文献后,对黄酮类化合物在糖尿病肾病防治中的多种作用及相关机制进行综述,以期为糖尿病肾病防治药物的研发提供参考。     

中医药对糖尿病肾病的治疗研究进展

糖尿病肾病(DN)又称糖尿病肾小球硬化症,为糖尿病常见的严重肾脏并发症,属中医"消渴"、"水肿"等范畴。西医目前尚无较为理想的治疗方法,而中医药在西医常规治疗基础上对糖尿病肾病的治疗已取得了较好的疗效,本文查阅总结了近几年有关中医药治疗糖尿病肾病的相关研究文献,从糖尿病肾病的病因、病理机制,中医药治疗的实验及临床研究等方面进行综述,探讨中医药对糖尿病肾病的防治方法及其优势。     

黄芪治疗肾脏疾病的研究进展

近年来,大量的医学研究证明中药黄芪具有抗炎抗氧化、改善肾小球滤过屏障、调节免疫系统、改善水钠代谢、抑制炎症因子、抗癌、抗菌等作用。目前中药黄芪在肾脏疾病中应用广泛,对糖尿病肾病、肾病综合征及IgA肾病等多种慢性肾脏病具有良好的治疗效果。为使黄芪治疗肾脏疾病的研究取得更大的突破和进展,本文将对黄芪在肾脏疾病中的临床应用及相关机制研究进行全面阐述。     

基于病证结合肠易激综合征动物模型构建方法及研究思路

构建病证结合动物模型是进行中医药研究比较理想的技术平台。目前,诸多学者在现代医学疾病动物模型基础上结合病因制作病证动物模型,制备了适宜的相应的肠易激综合征病证结合模型,体现中医对肠易激综合征辩证优势,促进了病证结合动物模型研究的发展,但仍存在着对证候评价主观性、重病轻证等问题。因此在病证结合模型复制、筛选、评价方面,在不断深入疾病发病机制及中医证候研究基础上,通过方证相关结合系统生物学研究方法,进行深入中医证候内涵相关研究,改进病证模型的研究、构建方法,病证结合动物模型制备思路更成熟,以阐明中医药的科学内涵。     

四氧嘧啶诱导小鼠糖尿病模型影响因素的研究进展分析

随着糖尿病发病率的不断提高以及糖尿病并发症对患者造成的危害越来越严重,对其进行积极有效的防治已经成为世界各国医学科学工作者的重要课题和研究热点。通过建立理想的糖尿病模型对糖尿病的发病机制、药物治疗效果、并发症预防、预后与转归等进行研究具有十分重要的意义。四氧嘧啶诱导小鼠糖尿病模型是临床常用的动物实验性模型,旨在通过动物模型的复制模拟人体的糖尿病变化规律,但是,在造模过程中不同的实验条件对于造模成功率有较大的影响。本文以相关文献的研究为基础,对四氧嘧啶诱导小鼠糖尿病模型的影响因素等进行分析,并探讨最佳实验条件,以提高造模的成功率和模拟糖尿病的准确性。     

四氧嘧啶诱导小鼠糖尿病模型影响因素的研究进展

糖尿病是严重危害人类健康的常见病、多发病,为探讨其发病机制、筛选有效的防治措施,采用动物模型开展实验研究已成为科技攻关的有效手段.现就影响四氧嘧啶诱导小鼠糖尿病模型的因素进行综述.     

植物多糖对糖尿病肾病肾脏转化生长因子β及蛋白表达影响的研究进展

目的:糖尿病肾病是糖尿病引起的危害性最大的一种严重慢性并发症,是糖尿病全身性微血管病变表现之一,晚期会导致严重肾功能衰竭,是糖尿病患者的主要死亡原因之一。糖尿病肾病病理机制复杂,其中转化生长因子β在糖尿病肾病的发病机制中占有重要地位[1],迄今尚无疗效确切的西药能延缓其进程。近20年来中医领域有关糖尿病肾病的研究取得了一定的进展[2],中医药治疗糖尿病肾病能减少西药的应用剂量和不良反应在降糖的同时具有改善肾功能的作用[3]。本文就植物多糖对糖尿病肾病肾脏转化生长因子β及基因表达的影响和多糖类成分对于糖尿病肾病防治的作用做相关综述,为今后糖尿病肾病的药物筛选提供一个指导性的方向。     

2型糖尿病小鼠模型的研究进展

2型糖尿病是一种受遗传因素和环境因素共同影响的疾病,动物模型在糖尿病及其并发症的发病机制、预防和治疗方法的研究中发挥重要作用,当前应用广泛的糖尿病小鼠模型主要有自发性糖尿病小鼠模型、实验性糖尿病小鼠模型和基因工程糖尿病小鼠模型。不同实验方法制备的糖尿病小鼠具有模拟临床糖尿病不同方面的特点,该文对各个模型的发病机制和生理特点等方面进行了阐述,以利于研究者根据各自不同的实验需求和目的选择合适的糖尿病小鼠模型来验证或实现科研设想。     

活性维生素D3与糖尿病肾病的关系研究进展

糖尿病肾病是糖尿病的主要并发症和终末期肾脏疾病的主要死亡原因之一,目前尚无有效地预防及治疗手段.研究显示活性维生素D3对肾脏具有保护作用,其作用机制可能是通过抗炎及抗纤维化实现的.该文对近年来国内外关于活性维生素D3对糖尿病肾病的保护机制及临床治疗进行了综合分析,这对于预防和寻找新的治疗糖尿病肾病方法具有重要意义.     

染料木素对肾脏疾病的防治作用及机制研究进展

目的:追踪染料木素(Gen)对肾脏疾病的防治作用及其作用机制的研究进展。方法:查阅近年来国内外相关文献,对Gen的肾脏疾病的防治作用及其作用机制的最新研究进展进行归纳、总结。结果:Gen主要通过调脂、抗氧化作用改善肾病综合征的肾脏病变;通过干扰多种促进肾小球系膜细胞增殖、细胞外基质积聚、炎症等生长因子的活性而发挥对肾小球的保护作用;通过抑制酪氨酸蛋白激酶(PTK)、修饰转化生长因子(TGF)-β1信号途径等发挥对肾小管间质疾病的防治作用;通过降低炎症细胞因子的表达、提高超氧化物歧化酶活力和总抗氧化能力、抑制糖基化产物等发挥对糖尿病肾病的防治作用。结论:Gen对几种肾脏疾病均显示较好防治效果。但目前对其机制的探讨主要为体外实验,尚需更多体内实验深入探讨。     

Criteria for creating and assessing mouse models of diabetic neuropathy

Diabetic neuropathy (DN) is a serious and debilitating complication of both type 1 and type 2 diabetes. Despite intense research efforts into multiple aspects of this complication, including both vascular and neuronal metabolic derangements, the only treatment remains maintenance of euglycemia. Basic research into the mechanisms responsible for DN relies on using the most appropriate animal model. The advent of genetic manipulation has moved mouse models of human disease to the forefront. The ability to insert or delete genes affected in human patients offers unique insight into disease processes; however, mice are still not humans and difficulties remain in interpreting data derived from these animals. A number of studies have investigated and described DN in mice but it is difficult to compare these studies with each other or with human DN due to experimental differences including background strain, type of diabetes, method of induction and duration of diabetes, animal age and gender. This review describes currently used DN animal models. We followed a standardized diabetes induction protocol and designed and implemented a set of phenotyping parameters to classify the development and severity of DN. By applying standard protocols, we hope to facilitate the comparison and characterization of DN across different background strains in the hope of discovering the most human like model in which to test potential therapies.     

Animal models and biomarkers of neuropathy in diabetic rodents

Diabetic neuropathy (DN) is a multifactor complication of diabetes. It is a late finding in type 1 diabetes, but can be an early finding in type 2 diabetes. The cause of DN is still unclear and, like other complications of diabetes, it may be the result of various pathological conditions. Animal models and biomarkers of DN have been extensively used in neuropathic research. The most useful model of DN should exhibit the key feature present in human pathology. Diabetic rodents show behavioral, functional, structural and molecular biomarkers and they are widely used as models to investigate the etiology of DN as well as to screen the efficacy of the potential therapeutic interventions. We have reviewed the different animal models and biomarkers of neuropathy in diabetic rodents of either type 1 or type 2 diabetes.     

Rodent animal models: from mild to advanced stages of diabetic nephropathy

Diabetic nephropathy (DN) is a secondary complication of both type 1 and type 2 diabetes, resulting from uncontrolled high blood sugar. 30–40 % of diabetic patients develop DN associated with a poor life expectancy and end-stage renal disease, causing serious socioeconomic problems. Although an exact pathogenesis of DN is still unknown, several factors such as hyperglycemia, hyperlipidemia, hypertension and proteinuria may contribute to the progression of renal damage in diabetic nephropathy. DN is confirmed by measuring blood urea nitrogen, serum creatinine, creatinine clearance and proteinuria. Clinical studies show that intensive control of hyperglycemia and blood pressure could successfully reduce proteinuria, which is the main sign of glomerular lesions in DN, and improve the renal prognosis in patients with DN. Diabetic rodent models have traditionally been used for doing research on pathogenesis and developing novel therapeutic strategies, but have limitations for translational research. Diabetes in animal models such as rodents are induced either spontaneously or by using chemical, surgical, genetic, or other techniques and depicts many clinical features or related phenotypes of the disease. This review discusses the merits and demerits of the models, which are used for many reasons in the research of diabetes and diabetic complications.     

温敏水凝胶Dex-PCL-HEMA/PNIPAAm的生物学性能

目的:对温度敏感水凝胶葡聚糖接枝聚己内酯-甲基丙烯酸羟乙酯共聚N-异丙基丙烯酰胺(Dex-PCL-HEMA/PNIPAAm)合成及体外降解进行研究,了解水凝胶的体外生物学性能.方法:利用自由基聚合法合成Dex-PCL-HEMA/PNIPAAm,并对其作LCST的测定、内部形貌观察、体外降解、体外控制释放胎牛血清蛋白(BSA).结果:水凝胶的较低临界溶解温度(LCST)为33.2～34.2℃;内部形貌观察到水凝胶的孔径随着Dex-PCL-HEMA的含量的增大而缩小;体外酶降解显示DN水凝胶在前3天降解比较快,在第4～16天间,DN1、DN2、DN3、DN4四种水凝胶的降解率依次增大,16天后基本上不再降解;DN Dex-PCL-HEMA/PNIPAAm凝胶体外释放BSA曲线显示前5小时内释放最快,此后逐渐减慢.结论:Dex-PCL-HEMA/PNIPAAm水凝胶保持了其良好的温度敏感性,体外实验显示生物相容性良好,因此可以作为动物实验的材料.     

罗格列酮联合洛沙坦对糖尿病肾病大鼠足细胞的协同保护作用

目的探讨罗格列酮联合洛沙坦对糖尿肾病(DN)大鼠足细胞的协同保护作用。方法制备DN大鼠模型,将动物随机分为DN模型组、罗格列酮干预组、洛少坦干预组及罗格列酮联合洛沙坦干预组,另设正常对照组。8周后观察尿蛋白排泄量,采用免疫组化、RT-PCR方法检测肾皮质nephrin、podocin蛋白及mRNA表达,采用透射电镜检测足细胞超微结构变化。结果(1)各干预组DN鼠尿蛋白排泄均减少。(2)联合干预组对足细胞超微结构及nephrin、podocin下调的改善作用优于单药干预组。结论罗格列酮与洛沙坦联合用药对DN大鼠肾脏保护作用优于单种药物治疗,其机制部分与改善足细胞超微结构及上调nephrin、podocin表达有关。     

The promise and pitfalls of animal and human models of relapse: comment on Leri and Stewart (2002)

F. Leri and J. Stewart (2002) recently presented results from an animal study of lapse and relapse in an attempt to model the human situation. The authors of this comment consider two criteria for evaluating the usefulness of animal models for studies of human relapse: (a) the extent to which the animal model captures the essential components of human lapse and relapse phenomena and (b) the extent to which the conceptualization guiding the animal model is congruent with modern research and theory on animal behavior in related preparations. The authors argue that F. Leri and J. Stewart's (2002) model, as of yet, does not meet the standards suggested by these criteria. However, features of this work may prove valuable for informing efforts to develop relapse paradigms in both human and animal research.     

自噬调节与特发性肺纤维化药物治疗研究进展

特发性肺纤维化（idiopathic pulmonary fibrosis,IPF）是一种病因复杂、与年龄相关的肺纤维化疾病,其发病过程表现出进行性与不可逆性,最终导致患者呼吸系统衰竭而死亡。近些年的研究证实自噬参与了IPF的发生发展。本文回顾总结了自噬和IPF相关的临床研究、动物和细胞模型研究以及基于自噬的药物治疗研究,希望对阐明IPF的病理机制和药物研发有所帮助。     

Metabolic activation capacity of neonatal mice in relation to the neonatal mouse tumorigenicity bioassay

The neonatal mouse tumorigenicity bioassay is a well-developed animal model that has recently been recommended as an alternative tumorigenicity bioassay by the International Conference on Harmonization (ICH) for Technical Requirements for the Registration of Pharmaceuticals for Human Use. There are sufficient data to conclude that this animal model is highly sensitive to genotoxic chemical carcinogens that exert their tumorigenicity through mechanisms involving the formation of covalently bound exogenous DNA adducts that lead to mutation. On the other hand, it is not sensitive to chemical carcinogens that exert tumorigenicity through a secondary mechanism. The metabolizing enzymes present in the neonatal mouse, particularly the cytochromes P450, are critical factors in determining the tumorigenic potency of a chemical tested in this bioassay. However, compared to the metabolizing enzymes of the adult mouse and rat, the study of the metabolizing enzymes in neonatal mouse tissues has been relatively limited.     

MiR-325-3p inhibits renal inflammation and fibrosis by targeting CCL19 in diabetic nephropathy

Diabetic nephropathy (DN), a common cardiovascular disease, has been a global health threat. MicroRNAs (miRNAs) have been proposed to frequently participate in the occurrence and development of DN, however, the role of miR-325-3p in DN remains uncharacterized. Our research aimed to explore the function and mechanism of miR-325-3p in DN. Bioinformatics analysis (Targetscan, http://www.targetscan.org ) and a wide range of experiments including RT-qPCR, CCK-8 assay, western blot, luciferase reporter assay, RNA immunoprecipitation (RIP) assays, urine protein and blood glucose assays, histology analysis and morphometric analysis were used to explore the function and mechanism of miR-325-3p and C-C motif chemokine ligand 19 (CCL19). CCL19 could facilitate the progression of DN by inhibiting cell viability and promoting inflammation and fibrosis in HK-2 and HMC cells. In addition, CCL19 was confirmed to be targeted and negatively regulated by miR-325-3p. Rescue assays validated that the impacts of miR-325-3p mimics on the viability, inflammation and fibrosis of HK-2 and HMC cells were recovered by CCL19 overexpression. To sum up, miR-325-3p inhibits renal inflammation and fibrosis by targeting CCL19 in a DN cell model and mice model, implying miR-325-3p as a possible therapeutic target for DN treatment.     

Reduction of Animal Sacrifice in Biomedical Science & Research through Alternative Design of Animal Experiments

Various upcoming techniques can be used in replacement of experiments requiring animal sacrifice or products of animal sacrifice. In many instances these techniques provide more reproducibility and control of parameter, compared to experiments involving animal or animal products. Use of these techniques can avoid the question of the animal sacrifice during experiment and subsequently permission of ethical approval. In silico simulation, informatics, 3D cell culture models, organ-on-chips are some innovative technology which can reduce the number of animals sacrifice. Scientist evolved some innovative culture procedures and production of animal friendly affinity reagents which are free from the product of animal sacrifice. Direct investigation on human body for treatment as well as further research, electronic health record is also helpful in the reduction of animals sacrifice in biomedical investigations. These techniques and strategies of research can be more cost effective as well as more relevant to various issues related to the human health. Some medical blunder has also been reported after the successful testing of drugs on animal’s model. Hence, the reliability of animal experiment in context with human health is questionable.Alternative to animal experiments help to reduce the number of animals required for research up to certain extent but is not able to eliminate the need for animals in research completely. Wisely use of animals in teaching & research is expected and the importance of animal experimentation in futuristic development in life science cannot be ignored.