体外培养小鼠足细胞表达COX-2的实验研究

目的: 研究环氧合酶-2(COX-2)在小鼠足细胞中的表达情况,为进一步研究嘌呤霉素氨基核苷(PA)诱导足细胞凋亡过程中特异性COX-2的表达,以及特异性COX-2抑制剂对足细胞的保护作用建立实验基础.方法: 将体外培养的条件永恒的足细胞复苏并传代培养,采用Western blot法分析COX-2在足细胞中的表达.结果: 在33℃增殖状态下,足细胞呈鹅卵石状,在37℃分化状态下的足细胞呈分叉状.正常足细胞在37 ℃分化14 d后,用低血清培养液培养后,随着时间延长,COX-2表达逐渐增多,24 h达最高,以后逐渐减少.结论: COX-2在足细胞上的表达呈时间依赖性.     

免疫荧光细胞化学和免疫酶细胞化学染色方法检测IgA肾病患者尿足细胞的效果比较

目的: 比较免疫荧光细胞化学和免疫酶细胞化学染色2种方法检测IgA肾病（IgAN）
患者尿足细胞的效果,为尿足细胞检测方法的选择提供依据。方法：收集43 例确诊为IgAN
患者（实验组）和10例正常对照研究对象（对照组）活检前连续3 d的晨尿各200 mL,离心上
清制成涂片。IgAN患者按Lee分级分成LeeⅠ～LeeⅤ组。采用抗人足细胞表面标记蛋白Podo
calyxin(PCX)单克隆抗体对尿沉渣涂片分别行免疫荧光细胞化学和免疫酶细胞化学染色,
荧光显微镜和普通光学显微镜下计数2组研究对象尿足细胞数;采用Spearman相关分析法分析2种方法检测IgAN患者尿足细胞数的相关性。结果：2种方法检测的对照组研究对象尿中未见足细胞,2种方法检测实验组研究对象尿中均可见足细胞;免疫荧光细胞化学法检测足
细胞阳性率和检出中位数低于免疫酶细胞化学法,2种方法检测尿足细胞阳性率和中位数比较差异均有统
计学意义(P<0.05);2种方法检查患者尿足细胞数呈明显的正相关关系（r=0.842,P<0.01）。结论：采用免疫酶细胞化学法检测同一份尿标本的效果优于免疫荧光细胞化学法。
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TNF-α-mediated podocyte injury via the apoptotic death receptor pathway in a mouse model of IgA nephropathy

BackgroundIgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis.MethodsForty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks.ResultsBSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice.ConclusionTNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway.     

TRPC6与肾脏疾病

瞬时受体电位阳离子通道（transient receptor potential channel, TRPC）作为瞬时受体电位（transient receptor potential, TRP）超家族中的一员,是一种非选择性的离子通道,在人体的各种组织、器官和细胞中均有表达。TRPC6基因突变致局灶节段性肾小球硬化(focal segmental glomerulosclerosis, FSGS),从而揭示了TRPC通道,尤其TRPC6与肾脏疾病的密切关系。TRPC6突变可引起细胞内钙离子浓度升高,也可直接影响肌动蛋白细胞支架组织,这些都是导致肾脏疾病的机制。     

基于多项理论认识下的中医药干预IgA肾病足细胞损伤研究进展

免疫球蛋白A（IgA）肾病是我国最常见的原发性肾小球疾病，临床主要表现为蛋白尿、血尿、高血压、水肿、高尿酸血症等，大部分患者起病隐匿，30%~40%患者在确诊10~20年后发展为终末期肾脏病，依赖透析或肾移植维持生命，危害巨大。蛋白尿是该病常见临床表现，多数患者表现为少量至中等量蛋白尿，10%~24%患者表现为大量蛋白尿，蛋白尿是影响IgA肾病肾功能进展的主要危险因素。足细胞是肾小球滤过屏障的末端部分，多种因素影响导致足细胞损伤后出现的足细胞足突融合、脱落等是IgA肾病常见组织学病变，且是导致蛋白尿及病程持续进展的关键因素。目前西医针对足细胞损伤的治疗缺乏针对性，干预手段有限，常使用糖皮质激素等药物治疗，不良反应较多。根据足细胞生理功能、损伤后的病理生理学改变及组织形态学改变等，认为其与中医“玄府理论”“肾络癥瘕”“络病理论”和“干血理论”等密切相关。越来越多研究显示，具有多环节、多途径、多靶点等作用特点的中医药干预IgA肾病足细胞损伤疗效明显，能起到保护足细胞、减少蛋白尿的作用，具有较好的应用与研究前景。该文系统总结了IgA肾病足细胞损伤机制与形态学改变、中医理论对足细胞损伤的认识以及中医药治疗IgA肾病足细胞损伤研究进展，以期为中医药干预IgA肾病足细胞损伤的进一步研究与应用提供参考。     

Podocyte expression of human phospholipase A2 receptor 1 causes immune-mediated membranous nephropathy in mice

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加味升降散对膜性肾病大鼠Notch信号通路及足细胞凋亡的影响

目的:通过研究加味升降散对膜性肾病(MN)模型大鼠Notch通路信号分子及下游凋亡相关基因的影响,探讨其抑制足细胞凋亡的分子机制.方法:将大鼠随机分为正常组,模型组,加味升降散组和贝那普利组,每组10 只.采用尾静脉注射阳离子化牛血清白蛋白(C-BSA)建立MN大鼠模型,加味升降散组和贝那普利组分别以27.3,0.00...     

The role of cell plasticity in progression and reversal of renal fibrosis

The need for novel insights into the mechanisms of progression of renal disease has become urgent during the last several years because of the increasing incidence of chronic renal disease worldwide. Independent of the underlying disease, the subsequent progression of renal fibrosis is characterized mainly by both an exaggerated synthesis and abnormal accumulation of extracellular matrix proteins produced by mesenchymal cells within the kidney. These cells are mainly myofibroblasts deriving from a variety of renal cells such as vascular smooth muscle, mesangial, resident stem, tubular epithelial, vascular endothelial cells or pericytes. The appearance of myofibroblasts is a reversible process, as suggested by studies in experimental models showing regression of renal fibrosis during therapy with antagonists and/or blockers of the renin-angiotensin system. An additional factor that can also affect the mechanisms of progression/regression of fibrosis is the plasticity of podocytes controlling glomerular filtration.