药物动力学房室模型的改进

 运用数学建模的方法,建立了一个改进的药物动力学的房室模型,利用临床数据和剩余浓度法对模型的参数进行估计,并验证了该模型的可行性及应用性．      

32例冷球蛋白血症患者临床、血清学和病理学特点

为提高对冷球蛋白血症(cryoglobulinemia, CG)的识别率和诊治率,通过回顾性分析方法,研究了2011年11月至2016年6月四川大学华西医院确诊的32例CG患者的临床、血清学及病理学资料。结果表明:32例CG患者中,自身免疫相关22例,感染相关14例,肿瘤相关5例,原发性1例。CG最常累及皮肤(25例,占78%),其次为甲状腺受累21例(66%)、肾脏受累20例(63%)、疲乏19例(59%)等。肿瘤、感染相关CG均以补体C3降低显著,自身免疫相关CG以补体C4降低多见。肾脏受累、肢端发绀均与补体降低呈负相关。CG皮肤受累的病理特征为小血管白细胞破碎性血管炎和(或)淋巴细胞性血管炎,肾脏受累可表现为各种病理类型的肾小球肾炎。肿瘤相关CG预后最差。可见CG涉及疾病谱广泛,累及器官系统多样,以皮肤受累最常见,CG的血清免疫学指标中,补体降低、γ球蛋白升高、类风湿因子(rheumatoid factor, RF)升高最常见,CG皮肤及肾脏受累的病理表现异质性高,早识别、早诊治有助于改善CG预后。     

三维可视化在肾脏领域的研究进展

三维可视化(three-dimensional visualization,3DV)是一项将二维转化为三维空间的新兴技术,主要利用影像、组织切片进行三维重建,可直观、立体展现宏观、微观结构.本文综述了3DV在肾脏外科微创、精准治疗中的应用,及在探究组织、细胞微观结构物质转运、生理机制中发挥的意义,为进一步临床应用及基础研究提供了依据.     

5 /6 肾切除小鼠中矿物质与骨代谢紊乱的特征

摘要: 目的通过制备5 /6 肾切除( 5 /6 Nx) 小鼠慢性肾脏病( CKD) 模型,观察小鼠成纤维生长因子23( FGF23) 及钙磷代谢指标,有助于研究矿物质与骨代谢紊乱的发病机制。方法28 只C57 雄性小鼠适应性饲养1 周后,切除模型组约5 /6 左肾,1周后切除右肾, 16 周后处死后收集血尿和肾脏组织标本,常规检测血尿FGF23、甲状旁腺素( PTH) 、活性维生素D、钙、磷等指标,观察肾脏病理。结果与假手术组和正常对照组相比,术后16 周5 /6 Nx 小鼠出现体质量减低,血清FGF23、PTH,血磷等异常升高,活性维生素D 水平显著降低,尿蛋白增加。肾脏病理发现系膜基质增生、胶原沉积及纤维化明显,和肾小球代偿性肥大。结论5 /6 Nx 小鼠可以出现明显的矿物质与骨代谢紊乱特征,是研究CKD 骨病合适的模型。     

Calmodulin-associated post-translational regulation of rat organic cation transporter 2 in the kidney is gender dependent

In this work, regulation of organic cation transporter type 2 from rat (rOCT2) stably transfected in HEK293 cells was investigated by microfluorimetry with 4-(4-(dimethylamino)styryl)-N-methylpyridinium as substrate. The transport mediated by rOCT2 was specifically stimulated by PKA, phosphatidylinositol-3-kinase, p56^lck tyrosine kinase, mitogen-extracellular-signal-regulated-kinase-1/2, calmodulin (CaM), and CaM-kinase-II. The regulatory pattern of rOCT2 differs markedly quantitatively and qualitatively from that of other OCT isoforms. Only CaM-dependent upregulation is conserved throughout the OCT family. For this reason, CaM regulation of rOCT2 was also investigated in isolated S3-segments (known to express only rOCT2) of male and female rat proximal tubules. Inhibition of CaM by calmidazolium significantly decreased rOCT2 activity (−49.0 ± 13.6%, n = 4) in male but not female (9.0 ± 13.0%, n = 4) rats. Real-time PCR and Western blot investigations of CaM expression in rat kidneys showed that male animals have significantly higher CaM expression. This is the first study describing post-translational gender-dependent rOCT2 regulation. Received 26 February 2009; accepted 16 March 2009     

Polycystic kidney diseases: From molecular discoveries to targeted therapeutic strategies

Polycystic kidney diseases (PKDs) represent a large group of progressive renal disorders characterized by the development of renal cysts leading to end-stage renal disease. Enormous strides have been made in understanding the pathogenesis of PKDs and the development of new therapies. Studies of autosomal dominant and recessive polycystic kidney diseases converge on molecular mechanisms of cystogenesis, including ciliary abnormalities and intracellular calcium dysregulation, ultimately leading to increased proliferation, apoptosis and dedifferentiation. Here we review the pathobiology of PKD, highlighting recent progress in elucidating common molecular pathways of cystogenesis. We discuss available models and challenges for therapeutic discovery as well as summarize the results from preclinical experimental treatments targeting key disease-specific pathways. Received 8 August 2007; received after revision 19 September 2007; accepted 2 October 2007     

MicroRNA与慢性肾脏病并发动脉粥样硬化相关性与中医药干预研究进展

动脉粥样硬化(As)引起的心血管疾病是慢性肾脏病(CKD)患者主要并发症和主要死亡原因之一。microRNA是一类小的非编码RNA,是参与基因调控网络的重要因子。国内外大量研究表明部分microRNA的异常表达可通过多种机制介导CKD及其心血管并发症如As的病理进程,被确定为CKD As的病理相关因子,应用microRNA作为疾病生物标志物的独特优势和CKD As潜在治疗靶点的作用是现代研究热点。中医认为CKD As病机正虚与邪实夹杂,具有本虚标实的特点,中医药通过调控microRNA干预CKD As符合传统“扶正祛邪”治疗原则与现代中医微观辨证理念,以microRNA为切入点研究中医药防治CKD As的具体机制具有重要意义。本文就国内外microRNA与CKD As病理机制的相关性以及中药复方、中药活性成分调控CKD异常microRNA防治As的作用机制研究进展进行了综述,以期为未来相关研究提供理论参考,以便开发更有效的治疗策略,为临床中医药治疗CKD As提供新的可能途径与干预靶点。     

泰和鸡肾脏的组织学和组织化学研究

本文采用H·E染色,PAS反应,PAS-AB反应及半薄切片甲苯胺蓝染色等方法,对泰和鸡肾脏进行了组织学和组织化学研究。结果表明:泰和鸡肾脏由数个肾小叶构成,每个肾小叶分为皮质和髓质2部分。肾单位包括肾小球、近曲小管、髓袢、远曲小臂和连接小管5部分。集合小管分为小叶周集合小管和髓质集合管2种,还观察到了球旁细胞和致密斑。对中性粘液物质和酸性粘液物质在肾脏内的分布作了初步描述。     

鳜暴发流行病病毒性病原研究

患病鳜肾脏、脾脏、肝脏、心脏、鳃中发现二十面体病毒粒子,肾脏和脾脏是其感染主要器官．成熟病毒粒子直径１５０ｎｍ,核心球状,直径１０５ｎｍ．受感染细胞肿大,直径为正常细胞３～４倍,细胞核萎缩,为正常细胞核直径１／３．病毒粒子部分纯化后,经腹腔人工感染,第７天开始死亡,１０ｄ内死亡率为１００％,表现与池塘养殖状态相同症状,并在人工感染鳜肾和脾中电镜观察发现大量相同病毒粒子,命名为传染性脾肾坏死病毒（ｉｎｆｅｃｔｉｏｕｓｓｐｌｅｅｎａｎｄｋｉｄｎｅｙｎｅｃｒｏｓｉｓｖｉｒｕｓ,ＩＳＫＮＶ）．     

Cleavage of des-Arg9-bradykinin by angiotensin I-converting enzyme from pig kidney cortex

Summary Fast and very slow hydrolyses of des-Arg⁹-bradykinin and angiotensin II by angiotensin I-converting enzyme were detected by high performance liquid chromatography. The Michaelis constants of the enzyme, K_m values, for des-Arg⁹-bradykinin and bradykinin were found to be 0.24 mM and 4.4 M, and the maximum velocities, V_max values (mol·min^–1·mg protein^–1) for these compounds to be 3.24 and 0.34, respectively. The enzyme also hydrolyzed Z-Gly-Pro-Gly-Gly-Pro-Ala to a tripeptide that was identified as dansyl-Gly-Pro-Ala by TLC on polyamide. These observations show that the enzyme hydrolyzes the peptides at the bond before the prolyl residue in the penultimate position.Acknowledgments. We thank Dr Kinzo Nagasawa of Kitasato University for encouragement in this work and Dr Ervin G. Erdös, University of Texas, Health Science Center, Dallas, for valuable discussion and suggestions.Abbreviations used: Z, carbobenzoxy; Bz, benzoyl; ACE, angiotensin I-converting enzyme; BK, bradykinin; HPLC, high performance liquid chromatography.