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。     

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     

混合稀土常乐对Wistar大鼠肾脏影响的实验研究

研究了长期口服混合稀土常乐对肾脏功能的影响.将120只雌、雄各半的Wistar大鼠平均分为对照组和2、5、20 mg/kg 3个剂量的给药组,连续以灌胃方式给药90 d,第91 d取血清,测试肌酐(碱性苦味酸法测试)、尿素氮(尿素酶电导法测试)、尿酸(终点法测试)和钙(离子选择电极法测试),用SPSS10.0软件对肌酐、尿素氮、尿素、钙的含量和尿素氮/肌酐比值进行one-way ANOVA方差分析.研究结果显示:①尿素含量:雌、雄两性大鼠差异均不显著(P>0.05).②尿素氮含量:雄性大鼠,2 mg/kg组的含量比对照组极显著增多,而20 mg/kg组比对照组极显著降低(P<0.01);雌性大鼠,5 mg/kg和20 mg/kg组均比对照组极显著降低(P<0.01),同时,2 mg/kg组雌性大鼠比雄性大鼠的含量显著降低(P<0.05).③肌酐含量:雌性大鼠和雄性大鼠与对照组相比差异均不显著(P>0.05).④钙含量:雄性大鼠各剂量组均比对照组极显著增多(P<0.01),雌性大鼠2 mg/kg组比对照组含量显著性增多(P<0.05).⑤BUN/CRE比值:雌、雄性大鼠在5 mg/kg和20 mg/kg组均比对照组极显著降低(P<0.01),2 mg/kg组的雌性大鼠比同剂量组的雄性大鼠极显著性降低(P<0.01).     

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。     

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.     

Endocytosis mechanism of P2Y2 nucleotide receptor tagged with green fluorescent protein: clathrin and actin cytoskeleton dependence

Extracellular nucleotides exert a large number of physiological effects through activation of P2Y receptors. We expressed rat P2Y₂ (rP2Y₂) receptor, tagged with green fluorescent protein (GFP) in HEK-293 cells and visualized receptor translocation in live cells by confocal microscopy. Functional receptor expression was confirmed by determining [Ca²⁺]_i responses. Agonist stimulation caused a time-dependent translocation of the receptor from the plasma membrane to the cytoplasm. Rearrangement of the actin cytoskeleton was observed during agonist-mediated rP2Y₂-GFP receptor internalization. Colocalization of the internalized receptor with early endosomes, clathrin and lysosomes was detected by confocal microscopy. The inhibition of receptor endocytosis by either high-density medium or chlorpromazine in the presence of UTP indicates that the receptor was internalized by the clathrin-mediated pathway. The caveolin- mediated pathway was not involved. Targeting of the receptor from endosomes to lysosomes seems to involve the proteasome pathway, because proteasomal inhibition increased receptor recycling back to the plasma membrane.Received 8 February 2005; received after revision 18 March 2005; accepted 11 April 2005     

Gamma-aminobutyric acid uptake by rat kidney brush-border membrane vesicles

Summary Brush-border membrane vesicles (BBMV) from rat kidney cortex possessed two uptake systems for -aminobutyric acid (GABA), a high affinity system (Km=10.9 M) and a low affinity system (Km=1203 M). Both uptake systems were inhibited by p-hydroxymercuribenzoic acid and ouabain, and by the action of neuraminidase, whereas the GABA analogs nipecotic acid, -alanine, 2,4-diaminobutyric acid and 4,5,6,7-tetrahydroisoxazolo-[4,5c]-pyridin-3-ol had no effect on the GABA uptake activity. The BBMW uptake systems were clearly different from the GABA transport systems present in brain tissue.     

Ultrastructural and seasonal aspects of the kidney lymphatic system of hibernating animals

Summary The kidney lymphatic system of bat, dormouse and marmot consists of intraparenchymal (interlobar, arcuate, interlobular) and extraparenchymal (capsular) vessels sharing common ultrastructural aspects. We did not observe medullary lymphatics. The qualitative and quantitative seasonal changes in the ultrastructure of the lymphatic endothelium represent not only a species-linked feature but also (and mainly) an evident seasonal fluctuation in lymph formation. Furthermore, these ultrastructural changes emphasize the important role played by the different mechanisms involved in the translymphatic movement of proteins and interstitial fluid with particular regard to the vesicular route and intraendothelial channels.     

肺癌组织学类型的光镜,电镜比较观察

对１８例肺活癌活检标本按照修订后的ＷＨＯ分类方法进行了光镜与电镜的对比观察。结果发现７／１８例肺癌的原光镜诊断得以修正，其中鳞癌为３／１０例，腺癌为２／２例，小细胞癌为２／５例，１８例肺癌中有７例表现出异质性，并在同一细胞内见到肺癌的双向分化特征。     

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.