糖尿病肾损伤早期诊断的尿液联合检测

目的 通过对糖尿病（DM）患者尿液中微量白蛋白（mAlb）、β2微球蛋白（β2-MG）、N-乙酰-β-D氨基葡萄糖苷酶（NAG）、转铁蛋白（TRF）等进行检测，探讨其联合检测对糖尿病肾损伤早期诊断的临床意义。方法利用免疫比浊法、酶法检测50例健康体检者及204例DM患者尿液中mAlb排泄率、β2-MG、NAG、TRF含量，尿蛋白定性及血BUN、CR测定，并分组比较。结果血BUN、CR及尿蛋白阴性糖尿病患者尿液中mAlb、β2-MG、NAG、TRF均明显高于对照组（P〈0．01），后四项联合检测较单项检测阳性率高。结论尿液联合测定有助于了解DM患者的肾损伤情况，其对糖尿病肾病（DN）的预防和早期诊断有重要意义。     

2型糖尿病肾病与脂代谢紊乱关系的探讨

目的探讨2型糖尿病(T2DM)患者糖尿病肾病(DN)与脂代谢紊乱的关系.方法检测了51例2型DM 并发DN患者的空腹血脂、载脂蛋白水平、空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹C肽、餐后2hC肽,与无DN的T2DM患者及正常人比较.结果 T2DM无DN组和DN组的甘油三脂(TG)、总胆固醇(TC)、载脂蛋白B(ApoB)、HbA1c、FPG显著高于正常对照组,同时DN组的TG、TC、PG 、HbA1c显著高于T2DM无肾病组.C肽测定值与24h尿微量白蛋白排泄水平(UAER)呈显著负相关性.结论脂代谢紊乱是影响2型糖尿病肾病发生发展的一项独立危险因素为防止T2DM患者DN的发生,除应重视控制血糖外,还应该注意血脂的控制.     

尿β_2-MG对2型糖尿病亚临床糖尿病肾病诊断价值的探讨

目的:探讨尿β_2-MG对2型糖尿病(DM)亚临床糖尿病肾病(DN)的诊断价值。方法:对尿常规、血尿素氨 (BUN)、血肌酐(Cr)正常的63例2型DM患者(亚临床DN组)分别进行血、β_2-MG和尿Alb放射免疫测定(RIA)。 结果:剔除3例血β_2-MG>4.5mg/L患者后分析发现,亚临床DN组尿β_2-MG、Alb显著高于正常对照组(P<0. 001);尿Alb阳性率与尿β_2-MG阳性率无显著性差异(P>0.05);尿β_2-MG与尿Alb检测结果显著正相关(r=0. 495,n=60,P<0.001)。结论:DN时肾小球、肾小管均易受损,且存在着密切的正相关关系,尿β_2-MG是诊断早期 DN的一项重要指标,与Alb联合检测,可以提高DN的早期诊断率,并能对DN时肾小球和肾小管受损的部位及程 度作出判断。     

Transgenic overexpression of a dominant negative mutant of FADD that, although counterselected during tumor progression, cooperates in L-myc-induced tumorigenesis

Activation of the so-called death receptors, e.g., CD95/Fas/Apo-1, is a potent stimulus to trigger apoptosis. Overexpression of the C-terminal FADD deletion mutant FADD-DN blocks death receptor-induced apoptosis, but despite this antiapoptotic activity, lck FADD-DN transgenic mice do not develop lymphomas. To analyze whether functional inactivation of FADD cooperates with Myc overexpression in tumorigenesis, lck FADD-DN transgenic mice were crossed with Emicro L-myc transoncogenic animals. While no tumors were detected in single transgenic FADD-DN or L-myc mice within 15 months, 5 of 17 (29%) FADD-DN/L-myc double transgenic animals developed lymphomas with an average latency period of 47 weeks. Protein analysis of FADD-DN/L-myc tumors showed, however, undetectable levels of FADD-DN protein. FADD-DN protein expression was again lost in 16 of 17 FADD-DN/p53 k.o. T-cell lymphomas, though no significant acceleration of tumorigenesis in P53-deficient lck FADD-DN mice compared to p53 k.o. animals was observed. These data suggest a strong counterselection against the FADD-DN protein during tumor progression, which could be explained by the cell cycle inhibitory activity of FADD-DN. Such counterselection would have to be compensated for by other antiapoptotic mutations, and indeed, strong upregulation of the antiapoptotic Bcl-2 family member Bcl-xL was found in one of the tumors. This in vivo mouse model demonstrates that an antiapoptotic protein involved in the onset of tumorigenesis is selected against and consequently lost during tumor progression because of its additional antiproliferative activity.     

糖尿病肾病中医分型肾脏叶间动脉彩色多普勒超声分析

借助彩色多普勒频谱图,对糖尿病肾病患者肾脏叶间动脉血流参数进行分析,探讨该病中医分型的客观指标。方法：选择糖尿病肾病３５例,将其分为气阴两虚及阴阳两虚组,于每位患者双肾叶间动脉测量：收缩期峰值血流速度（ＶＳ）、舒张期末血流速度（ＶＤ）、平均血流速度（ＭＳ）、搏动指数（ＰＩ）、阻力指数（ＲＩ）。结果：气阴两虚组ＰＩ、ＲＩ值明显高于正常组（Ｐ＜０．０１）,阴阳两虚组ＰＩ、ＲＩ明显高于气阴两虚组（Ｐ＜０．０５）;阴阳两虚组ＶＤ值高于气阴两虚组及正常组（Ｐ＜０．０１）;气阴两虚组与正常组比较无统计学差异。结论：糖尿病肾病气阴两虚及阴阳两虚组中ＰＩ及ＲＩ,可以作为糖尿病肾病中医分型的客观指标。     

In-situ hybridization studies of protein kinase C α and β I isoforms in human diabetic nephropathy

Background. Hyperglycemia is the most important contributor to the development of diabetic nephropathy (DN). The activation of protein kinase C (PKC) caused by hyperglycemia is implicated in the pathogenesis of DN. PKC, which comprises a family of enzymes, plays a role in many signal transduction pathways and is involved in the regulation of cell growth and differentiation. However, the precise role of PKC in the progression of human DN is not fully understood. Methods. To evaluate the pathological role of PKC in DN, we examined the mRNA expression levels of PKC α and PKC β I isoforms in normal renal tissues and in renal tissues affected by DN. Tissues from open renal biopsies were obtained from 20 type 2 diabetic patients with DN. The expression levels of PKC α and PKC β I mRNA in kidneys with DN and in normal human kidney (NHK) were evaluated by in-situ hybridization, using digoxigenin-labeled oligonucleotide probes. Results. Cells positive for PKC α and β I mRNA were mainly observed in glomeruli, and some mRNA was also detected in the tubulointerstitium. The percentages of glomerular cells positive for PKC α and β I mRNA were higher in kidneys with DN than in NHK. In the glomeruli of kidneys with DN, the percentage of cells positive for PKC β I mRNA, but not the percentage of cells positive for PKC α mRNA, tended to be decreased with the degree of mesangial expansion. Conclusions. Our results suggest that the expression of mRNA for PKC α and/or β I may be associated with the progression of DN. Received: March 26, 2001 / Accepted: September 17, 2001     

The biochemical pharmacology of renin inhibitors: Implications for translational medicine in hypertension, diabetic nephropathy and heart failure: Expectations and reality

The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, Diabetes mellitus (DM), chronic kidney disease (CKD) and chronic heart failure (CHF). Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEi or ARBs remain high. Small molecules that directly inhibit renin (DRI) and are orally active have also been developed and one such drug, aliskiren, was introduced into clinical use for treatment of hypertension in 2007. Further clinical trials aimed to expand the therapeutic use of aliskiren are in progress for CKD-DM and CHF. In this review we analyze and review the translational medicine prospects of aliskiren in respect to the biochemical pharmacology of the RAAS, the marketed RAAS modulators and the new emerging science regarding the role of prorenin, renin and renin receptors in cardiovascular biology and disease. The information already gained with aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEis and ARBs, their potential added value in combination with other RAAS modulators and other unproven benefits in relation to prorenin and renin receptor biology. This review will also indicate basic and clinical research needs that are critical to determine whether DRIs can provide meaningful added medical benefits over contemporary medicines that regulate the RAAS, and the need to identify patients that are more likely to benefit from DRIs and any possible long term adverse effects.     

从脏腑气血阴阳辨治糖尿病性肾病

糖尿病性肾病其病机为虚实夹杂,本虚为肝、脾、肾气血阴阳失调;标实多为燥热、湿浊、瘀血、水毒。根据疾病所处的病理阶段及临床表现,可分为阴虚燥热证、肝肾阴虚证、气阴两虚证、阴阳两虚证、脾肾阳虚证及肾阳衰微证等6型,治疗上强调早期治疗,辨证施治,兼顾标本虚实,发挥中医药治疗本病的优势,使病情长期稳定,延缓疾病进程。