糖基化终产物与糖尿病肾病

糖尿病肾病 (DiabeticNephropathy ,DN )主要指毛细血管间肾小球硬化症 ,是糖尿病 (DiabetesMellitus ,DM )常见而难治的微血管并发症 ,已成为DM病人的主要死因之一。DN的主要病理变化是肾脏高灌注、高滤过 ,肾小球基底膜(GBM)增厚和以肾小球系膜区为主的细胞外基质 (ECM )积累 ,导致弥漫性或结节性肾小球硬化 ,出现蛋白尿、高血压、肾衰竭等功能紊乱。DN的发生机制目前尚不十分明确 ,现将近年来对DN发病机制的中医认识及糖基化终产物在糖尿病肾病中的作用作一综述。　　 1　中医病因病机认识1.1　湿滞、脾虚论　杨军[1] 认为消渴…     

细胞外基质增殖在糖尿病肾病的作用

糖尿病肾病(DN)是糖尿病(DM)的主要慢性并发症,病理特点是肾脏高灌注,肾小球基底膜(GBM)增厚和以肾小球系膜区为主的细胞外基质(ECM)积聚,导致弥漫性或结节性肾小球硬化,出现蛋白尿、高血压、肾功能衰竭等功能紊乱。DN的发生机制目前尚不清楚,可能是代谢异常,血流动力学障碍或遗传因素。但不论其机制是什么,DN病人均出现了ECM的生化和结构改变。因此对ECM的研究可提高对DN发病机理的认识,对DN防治具有重要意义。近年对ECM的研究已取得了很大进展,我们主要综述DM状态对ECM的影响和ECM与DN发生发展的关系。     

糖尿病肾病时脂蛋白(a)血症和肾损害

糖尿病(DM)及糖尿病肾病(DN)均易伴发高脂血症,是肾脏病的危险因子,可引起肾脏结构及功能损害,可使肾小球、肾小管-间质病变加重,最后导致肾小球硬化及肾衰竭,本文就Lp(a)与DN之间的关系,作一简要复习.     

中西医结合治疗糖尿病肾病近况

糖尿病肾病(DN)是指与糖尿病(DM)代谢异常有关的糖尿病性肾小球硬化症,是糖尿病常见的严重并发症之一,严重影响着患者的预后,据报道糖尿病肾病的发病率约占糖尿病病人的35%～40%,在Ⅰ型糖尿病(IDDM)中约50%患者最终死于肾衰竭,在Ⅱ型糖尿病(NIDDM)中DN也是三大主要死亡原因之一.DN的研究与防治越来越引起有关学者的重视,有关这方面的报道和研究不断出现.笔者就近年来有关中西医结合治疗本病的概况综述如下.     

足细胞与糖尿病肾病

糖尿病(diabetes mellitus,DM)的发生率在世界范围内迅速上升[1],而糖尿病肾病(diabetic nephropathy,DN)是糖尿病最严重的慢性并发症之一.在西方国家,需行肾脏替代治疗的患者中,约35%为DN患者[2].我国目前约有4 000万人面临糖尿病危胁,DN占终末期肾衰竭患者的15%[3].DN的主要病理特征是肾小球细胞外基质(extracellular matrix,ECM)堆积,系膜增宽、基底膜(glomerular basement membrane,GBM)增厚,肾小球硬化及伴肾间质纤维化.DN的发病机制仍未完全明确,近年来,肾小球滤过屏障的结构和功能改变,尤其是作为肾小球滤过屏障结构成分的足细胞在DN发生发展中的作用,成为研究热点.本文拟就这方面的研究进展做一综述.     

P-选择素、内皮细胞-巨噬细胞黏附与糖尿病肾病

糖尿病（DM）是常见病、多发病，患病人数随着人民生活水平提高、人口老化与生活方式的改变而迅速增加。糖尿病肾病（DN）已成为终末期肾衰主要原因之一，目前近40％的透析患者是DN。DN发病机制尚未明确，治疗仍然是一大难题。肾脏是典型的微血管器官，DN是DM微血管并发症与重要死因。DN基本病理改变包括肾小球肥大、细胞外基质堆积、基底膜增厚与肾小球硬化，单核／巨噬细胞在肾组织广泛浸润是DN进展的组织学特点。新近观点认为，DM是一种慢性炎症，P-选择素及其介导的内皮细胞-巨噬细胞黏附在DN机制中有重要意义。     

糖尿病肾病发病机制研究进展

在糖尿病人群中糖尿病肾病(DN)发病率约为20％～40％,是糖尿病的主要并发症和死亡原因.近年来随着糖尿病患者人数的快速增长,DN的发病率逐年上升,在一些国家或地区已经成为终末期肾病(ESRD)的首位原因.DN早期主要的病理改变为肾小球肥大,肾小球和肾小管基底膜的增厚及系膜区细胞外基质(ECM)的进行性聚积;后期是肾小球、肾小管间质纤维化,最终导致蛋白尿和肾衰竭.DN的发病机制复杂,其确切机制尚未明确,目前的研究结果提示代谢紊乱、血流动力学改变、炎性反应机制、细胞因子、氧化应激、遗传因素、激肽系统及自噬等多种因素参与了DN的发病.现将近年来有关DN发病机制的最新研究成果综述如下.     

糖尿病肾病发病机制的研究进展

糖尿病肾病(DN)是糖尿病(DM)的严重微血管并发症之一。以基底膜(GBM)增厚、系膜区扩张、胞外基质堆积为病理特征,是引起终末期肾衰的重要原因,也是DM病人的主要死亡原因之一。DN的发生与肾小球的血流动力学改变、多元醇代谢途径异常、蛋白非酶糖化和大分子糖化终末产物(AGEs)的生成、细胞因子的异常表达及脂代谢紊乱等因素密切相关。     

2型糖尿病肾病患者肾小球基底膜厚度与肾功能的相关性分析

<正>我国成人糖尿病患病率已达11. 6%,城市患病率高达14. 3%[1,2],而近几年我国糖尿病肾病(diabetic nephropathy,DN)的患病率显著增加,社区2型糖尿病患者DN患病率约30%～50%,1型糖尿病患者DN患病率约为30%[3,4]。在慢性肾脏病(chronickidneydisease,CKD)肾活检结果中DN诊断占第二位(20. 76%),而我国50岁～60岁中老年人群中DN是导致终末期肾病(end-stage renal disease,ESRD)首因[5,6]。一些生物标志物如血清脂蛋白、β-跟踪蛋白(βTP)[7]等都有助于临床医生早期评定T2DM肾损害患者发生DN的可能性,但典型的临床症状和肾活检仍是DN的主要诊断依据。在T1DM和T2DM患者中肾小球基底膜(glomerular basement membrane,     

糖肾冲剂配合厄贝沙坦治疗糖尿病肾病的临床观察

糖尿病肾病(DN)是糖尿病(DM)严重的并发症之一,病变可累及肾血管、肾小球、肾小管和肾间质,约30%糖尿病发展为糖尿病肾病,已成为目前糖尿病病人死亡的主要原因.糖尿病肾病为难治病之一,已为国内外学者所公认.2000年6月～2003年12月,我们采用中西医结合治疗糖尿病肾病取得了较好疗效,现将结果报告如下.     

Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency

The protein and molecular characteristics of variants of the alpha1-antitrypsin (AAT) gene are described, and available data on the genetic epidemiology of AAT deficiency are presented.     

Deficiency of TBL1XR1 causes asthenozoospermia

Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is an evolutionarily conserved protein related to spermatozoa. To clarify its role and mechanism of action in spermatozoa, qRT-PCR was used to analyse the expression of TBL1XR1 in human spermatozoa and mouse testes. The mice were established as an animal model by injecting the mice testes with small interfering RNA against TBL1XR1 or control siRNA. Our results indicated that deficiency of TBL1XR1 in mice reduced the motility of spermatozoa and disrupted the histone-to-protamine transition. We also found the decreased expression of TBL1XR1 in the spermatozoa of human patients with asthenozoospermia (AZ) compared with that in the spermatozoa of healthy males. Moreover, we carried out chromatin immunoprecipitation analyses and found that genes downstream of TBL1XR1 were related to sperm motility. Thus, TBL1XR1 might be related to sperm motility and might function through its downstream genes. Our data highlight the role of TBL1XR1 involved in spermatozoa and provide new molecular insights into the intricate systems required for male fertility.     

手术创伤中腹膜组织Sp1、COL1A1和TIMP-1的表达

目的　探讨人手术创伤腹膜组织中核转录因子Sp1激活 ,COL1A1和TIMP 1表达变化与腹膜纤维化之间的关系。方法　采用凝胶电泳迁移率改变分析法 (EMSA)检测手术创伤后不同时间的腹膜组织核转录因子Sp1的表达水平 ,WesternBlot检测COL1A1和TIMP 1蛋白表达 ,Masson染色观察腹膜组织中胶原纤维的变化。结果　Sp1在手术创伤后 0 .5h被活化 ,随着手术时间延长Sp1活性逐渐增强 ,至创伤后 4h时达高峰 ,同时创伤腹膜组织中的COL1A1和TIMP 1蛋白表达水平逐渐升高 ,存在差异显著性 (P <0 .0 1)。在手术创伤期内随手术时间的延长腹膜组织中胶原纤维增加。结论　核转录因子Sp1活化导致Ⅰ型胶原合成增加 ,细胞外基质降解减少 ,从而启动腹膜纤维化进程。     

IgA肾病患者C1GALT1C1基因的体细胞突变筛查

目的 探讨IgA肾病（IgAN）患者β1,3半乳糖转移酶的分子伴侣Cosme编码基因C1GALT1C1基因体细胞突变情况。方法 27例IgA肾病患者及19例正常健康对照作为研究对象。提取研究对象外周血基因组DNA,扩增C1GALT1C1基因的编码区,采用PCR产物直接测序的方法进行突变筛查。然后,分离其中15例IgA肾病患者及7例健康男性对照的外周血B淋巴细胞,提取DNA。对C1GALT1C1基因编码区进行扩增,PCR产物进行克隆,各挑选平均8～10个克隆进行体细胞突变筛查。结果 46例个体全血基因组DNA的PCR扩增产物测序发现,2例患者及1例健康对照存在外显子T393A变异,次等位基因频率（MAF）为6．9%[SNP数据库（dbSNP）报告为9．5%]。B淋巴细胞DNA序列分析显示,在22例个体（15例IgA肾病患者,7例健康对照）送检的总共202个克隆中,未发现新的突变和多态性位点。结论 C1GALT1C1基因编码区T393A多态位点在本研究人群中为唯一发现的多态性位点,其次等位基因频率（MAF）较既往报道略低。本研究尚未发现IgA肾病患者B淋巴细胞存在体细胞突变。     

Evaluation of the influence of polymorphic variants CYP1A1 2B, CYP1B1 2, CYP3A4 1B, GSTM1 0, and GSTT1 0 in prostate cancer

Background/objectiveGenetic polymorphisms in cytochrome P-450 (CYPs) and glutathione S-transferase (GSTs) genes can influence the appearance of tumors by the formation of new enzymes with altered activities. In the present study, 5 polymorphic variants were examined in 154 patients with prostate carcinoma and in 154 controls.Materials and methodsDNA analysis was carried out through PCR-based methods. The statistical methods used were odds ratio and confidence interval (95% CI), χ², Fisher, and Mann-Whitney.ResultsThe study showed absence of association for CYP1A1*2B, CYP1B1*2, GSTM1*0, and GSTT1*0. The statistical analysis implied a positive association of variant CYP3A4*1B for prostate cancer. The combined analysis of CYP1A1*2B, CYP1B1*2, and CYP3A4*1B genotypes showed positive association. The analysis of histopathologic parameters detected statistically significant differences for Gleason score and biochemistry recurrence risk. The presence of the GSTT1*0 genotype in red meat consumers increased the risk for this disease.ConclusionSome polymorphic variants analyzed can influence the development and the progression of prostate cancer.     

The HLA-DPB1--associated component of the IDDM1 and its relationship to the major loci HLA-DQB1, -DQA1, and -DRB1

The major histocompatibility complex (MHC) HLA region on chromosome 6p21 contains the major locus of type 1 diabetes (IDDM1). Common allelic variants at the class II HLA-DRB1, -DQA1, and -DQB1 loci account for the major part of IDDM1. Previous studies suggested that other MHC loci are likely to contribute to IDDM1, but determination of their relative contributions and identities is difficult because of strong linkage disequilibrium between MHC loci. One prime candidate is the polymorphic HLA-DPB1 locus, which (with the DPA1 locus) encodes the third class II antigen-presenting molecule. However, the results obtained in previous studies appear to be contradictory. Therefore, we have analyzed 408 white European families (200 from Sardinia and 208 from the U.K.) using a combination of association tests designed to directly compare the effect of DPB1 variation on the relative predisposition of DR-DQ haplotypes, taking into account linkage disequilibrium between DPB1 and the DRB1, DQA1, and DQB1 loci. In these populations, the overall contribution of DPB1 to IDDM1 is small. The main component of the DPB1 contribution to IDDM1 in these populations appears to be the protection associated with DPB1*0402 on DR4-negative haplotypes. We suggest that the HLA-DP molecule itself contributes to IDDM1.     

Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer

BACKGROUND: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study. METHODS: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10). CONCLUSIONS: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.     

压力-流率测定中尿道内置测压导管对尿流率的影响

目的　探讨尿道内置测压管在压力 流率测定中对尿流率的影响。　方法　对 4 4例良性前列腺增生 (BPH)患者进行自由尿流率和压力 流率测定。压力 流率测定中尿道内放置 7F测压导管。统计学分析比较自由尿流率和置管后尿流率的变化。　结果　 4 4例患者自由尿流率和带管尿流率的排尿量分别为 (174 .72± 74 .6 2 )ml和 (186 .4 8± 6 9.71)ml(P >0 .0 5 )。最大自由尿流率(9 .5 5± 4 .10 )ml/s ,最大带管尿流率 (7.32± 3.2 8)ml/s(P =0 .0 0 0 )。最大尿流率下降值为 (2 .2 2± 3.0 7)ml/s。膀胱出口梗阻 (BOO) 0～Ⅰ级、Ⅲ级和Ⅳ级时自由尿流率和带管尿流率两者差异有显著性意义 (P <0 .0 5 ) ,BOOⅡ级、Ⅴ～Ⅵ级时自由尿流率和带管尿流率差异无显著性意义 (P >0 .0 5 )。　结论　尿道内置 7F测压导管可影响最大尿流率测定值。