血栓调节蛋白在糖尿病微血管病变中的变化

目的探讨血浆血栓调节蛋白（ＴＭ）在糖尿病性肾病患者中的变化以了解其在微血管病变发病中的意义。方法检测５８例２型糖尿病患者血浆ＴＭ与内皮素（ＥＴ）的水平,并与３０例正常人进行比较。结果（１）糖尿病组血浆ＴＭ水平明显高于正常对照组（Ｐ＜０．００１）,其中临床糖尿病肾病组血浆ＴＭ水平明显高于早期糖尿病肾病组（Ｐ＜０．００１）及尿白蛋白正常的糖尿病组（Ｐ＜０．０１）;（２）血浆ＴＭ水平与尿白蛋白排泄率、ＥＴ水平呈显著正相关（ｒ＝０．５３９０和０．５６５０,Ｐ均＜０．００５）。结论血浆ＴＭ水平测定对２型糖尿病性肾病的早期诊断和病情分析有重要的临床价值。     

血栓调节蛋白与糖尿病肾病

血栓调节蛋白(TM)是位于血管内皮细胞表面的糖蛋白，内皮细胞损伤时，血浆可溶性TM(PTM)水平升高，PTM是反映内皮损伤的一个分子标记物。糖尿病并发微血管病变尤其是糖尿病肾病(DN)时，PTM水平显著升高。内皮细胞损伤伴随着DN的整个发展过程，它的出现甚至早于DN微量白蛋白尿的出现。测定PTM水平对早期识别DN时血管内皮损伤程度以便早期治疗DN有重要的临床意义。     

血浆血栓调节蛋白与糖尿病血管病变的关系

目的　研究糖尿病并发症和无并发症血浆血栓调节蛋白 (PTM)水平及其临床意义。方法　用 EL ISA法检测 PTM的水平。结果　糖尿病并发症组 PTM(38.14± 12 .89) μg/ L显著高于无并发症组 (2 2 .11± 6 .5 8) μg/ L,P <0 .0 1,无并发症组与健康对照组 (2 0 .2 3± 7.5 4) μg/ L 几乎处于同一水平。并发症中 ,微血管病变组 PTM水平 (43.5 1± 13.2 8)μg/ L最高 ,明显高于大血管病变组 (31.89± 8.2 5 )μg/ L ,P <0 .0 1,且 PTM水平随 2 4h尿白蛋白排泄量增加而升高。相关分析提示 PTM与血糖 (r=0 .0 36 2 )、胆固醇 (r=- 0 .0 2 2 9)、甘油三酯 (r =0 .0 32 5 )、血浆纤维蛋白原 (r=0 .2 112 )、纤维蛋白降解产物 (r =- 0 .0 2 2 9)和年龄因素 (r=0 .2 34 1)均无相关性。结论　测定 PTM可以评估糖尿病血管内皮细胞的损伤及其程度和判断血管并发症的有无及其类型     

血栓调节蛋白检测在狼疮性肾炎血管病变中的意义

目的：探讨狼疮性肾炎(LN)患者血浆可溶性血栓调节蛋白(sTM)水平和肾组织TM免疫组化染色特点，分析其与系统性红斑狼疮活动度(SLEDAI)、血管病变、肾功能、蛋白尿、肾组织病理类型之间的关系。方法：60例经肾穿刺活检明确诊断的LN患者，采用酶联免疫吸附法(ELISA)检测血浆sTM水平，免疫组化染色检测肾小球和间质血管TM的表达。结果：Ⅱ型LN患者血浆sTM水平与正常对照组相近，Ⅳ型LN患者血浆sTM水平显著高于Ⅱ型LN；而合并有血栓性微血管病变的LN患者血浆sTM水平显著高于Ⅳ型LN，血浆sTM水平与狼疮的病变活动度和血清肌酐水平呈正相关，与蛋白尿多少无关。肾组织TM免疫组化染色示Ⅳ型LN肾小球与血管TM染色强度强于Ⅱ型LN；合并血栓性微血管病变LN患者肾小球与血管TM的染色强度与Ⅳ型LN相似。结论：血浆sTM水平与SLEDAI、血管病变轻重、肾功能损害程度及肾组织病变类型有关。肾小球和肾间质血管的TM表达强度与LN病理类型有关，但不能反映血管病变的轻重。血浆sTM水平不仅反映SLE疾病活动性，而且与LN的血管病变严重程度有关。血浆sTM水平可作为LN血管病变程度的指标，为指导治疗、判断预后提供依据。     

血栓调节蛋白在糖尿病大鼠心肌中的表达及意义

目的探讨STZ诱导的糖尿病大鼠心肌组织中血栓调节蛋白(TM)的表达及意义,为糖尿病心肌病(DCM)的防治提供新的靶向。方法从50只SD大鼠中随机选取32只采用一次性腹腔注射链脲佐菌素(STZ)制备糖尿病大鼠模型,剩余18只作为正常对照。每日观察大鼠进食、饮水等一般状况,每周固定时间测量体重、血糖及尿糖。分别在2、8、12 w末分批处死一定数量两组大鼠。分别检测各批大鼠的心脏指数(HW/BW)、血糖、血脂;采用透射电镜观察心肌组织超微结构的改变;免疫组化方法观察心肌组织中TM的蛋白表达;通过RT-PCR检测TM mRNA的表达水平。结果与正常对照组相比,2 w末模型组心脏指数无明显差异;8、12 w末心脏指数均显著增加,且12 w高于8 w(P<0.01)。模型组各时间段各项生化指标均高于正常对照组(P<0.01),各项指标变化由低到高排列顺序为2、8、12 w末。2 w末模型组大鼠未见明显病理变化;8、12 w末模型组大鼠出现心肌细胞肥大、排列紊乱、细胞外间质增多,线粒体肿胀、嵴断裂、溶解等病理变化;12 w末模型组大鼠上述病理变化较8 w末模型组更加明显。免疫组化显示,模型组TM表达明显高于正常对照组(P<0.01);组间比较阳性表达由低到高顺序依次是2、8、12 w末。与正常对照组相比,模型组大鼠心肌组织中TM mRNA的表达明显增高(P<0.01),其中,12 w末表达最强,其次是8,2 w末表达最弱。结论 TM在糖尿病大鼠心肌组织中呈时间依赖性高表达,并与病程呈正相关,显示其可能在DCM的发生、发展中发挥重要作用,这为该病的防治提供了新的靶向。     

促血管生成素1/促血管生成素2的比值与血管病变的关系

促血管生成素家族中促血管生成素1和促血管生成素2分别都能促进血管内皮细胞存活,但同时出现时,促血管生成素2拮抗促血管生成素1的内皮保护作用.促血管生成素1与促血管生成素2的比值与动脉粥样硬化病变、循环系统胚胎发育疾病、血管炎症病变以及糖尿病的血管并发症都密切相关.维持促血管生成素1与促血管生成素2的稳态平衡,或者使其比值向有利方向倾斜,才能发挥促血管生成素家族最有力的血管维护功能.     

血管生成素样蛋白2在糖尿病肾病中的表达及意义

目的：观察一种新发现的血管生成相关生长因子-血管生成素样蛋白2（ANGPTL2）在糖尿病肾病（diabetic nephropathy，DN）肾小球中的表达特征，并对其在DN发生发展过程中可能的作用机制进行初步探讨：方法：采用肾活检组织肾小球微分离技术结合半定量RT—PCR方法，观察24例2型DN患者肾小球中ANGPTL2 mRNA表达情况，以8例移植供肾活检组织作正常对照：并将其表达水平与DN患者临床病理指标进行相关分析。结果：DN患者肾小球ANGPTL2表达阳性率显著高于对照组（95％vs38％，χ^2=15．9，P〈0．01）。在表达明显上调（〉2倍）的患者中，肾小球做血管瘤、内皮细胞炎性浸润与泡沫化变性的发生率明显少于其他患者（22％vs66％；11％vs3％；11％vs53％；P〈0．05）。结论：ANGPTL2是一种血管生成相关的内皮细胞生长调节因子，参与DN微血管病变的发生机制.该因子在糖尿病肾小球中表达的上调可能是内皮损伤与血管重构过程中的一种应激性反应，具有维持内皮细胞功能与毛细血管正常结构的保护性作用.     

血管生成素样蛋白2在糖尿病大鼠肾脏中的表达及其干预研究

目的观察厄贝沙坦对血管生成素样蛋白2(ANGPTL2)在糖尿病大鼠肾脏中表达的影响及作用机制。方法 50只SD雄性大鼠随机分为正常对照(NC)组10只和实验组40只。实验组给予高糖高脂喂养联合小剂量链脲佐菌素建立T2DM大鼠模型,最终建模成功30只,随机分为糖尿病(DM)组15只和厄贝沙坦(DI)组15只。分别检测8周和12周时体重(BW)、BP、肾重(KW)、血糖、血肌酐(Scr)、BUN、24hUAlb水平。镜下观察肾组织病理改变,免疫组织化学染色法、RT-PCR检测肾组织ANGPTL2mRNA及蛋白表达的变化。结果 DM组24hUAlb水平高于DI组和NC组[8周:(7.43±0.36)vs(5.27±0.22)vs(0.74±0.06)mg/24h;12周:(7.84±0.32)vs(5.11±0.14)vs(0.74±0.08)mg/24h,P<0.05];DM组8周和12周ANGPTL2mRNA的表达水平较NC和DI组升高(P<0.05)。结论 ANGPTL2在糖尿病大鼠肾脏的表达量逐渐升高,而厄贝沙坦可降低其表达。     

促血管生成素1、2及Tie-2受体mRNA在肺腺癌中的表达

促血管生成素 1(Ang 1)、促血管生成素 2 (Ang 2 )及它们的内皮细胞特异性酪氨酸激酶受体 (Tie 2 )为肿瘤血管生成的重要调节因子[1] 。我们采用逆转录 多聚酶链反应 (RT PCR)结合计算机图像分析技术 ,对肺腺癌和癌旁肺组织Ang 1、Ang 2及Tie 2的mRNA的表达进行半定量分析 ,观察Ang 1、Ang 2及Tie 2在肺腺癌中表达水平 ,探讨 3者在肺腺癌肿瘤血管生成中的作用。材料与方法　病例来源及标本收集 :2 0 0 0年 1～ 10月 ,我院收治经手术切除病理证实肺腺癌 4 3例。男 2 8例 ,女 15例。年龄 35～ 70岁 ,平均年龄 5 6岁。临床分期 :Ⅰ期 1…     

促血管生成素-1对糖尿病大鼠肾脏色素上皮衍生因子和血小板反应蛋白-1基因表达的影响

目的 观察色素上皮衍生因子（PEDF）、血小板反应蛋白-1（TSP-1）在糖尿病大鼠肾脏的表达变化,探讨促血管生成素-1（Ang-1）对上述因子的影响. 方法 将雄性SD大鼠分正常对照（NC）组、DN组、空载处理（BV）组、Ang-1处理（AV）组.采用STZ腹腔注射诱导大鼠DN模型.成模8周后尾静脉注射Ang-1腺病毒载体.多时点检测24 hUAlb和肾组织PEDF、TSP-1蛋白及mRNA表达水平.结果 DN、BV、AV组24 hUAlb均升高,其中AV组于20周后降低（P＜0.05）.DN、BV、AV组肾组织PEDF蛋白及mRNA表达下调,TSP-1表达上调（P＜0.05）,其中AV组12周后肾组织PEDF和TSP-1mRNA及蛋白表达变化较DN、BV组改善明显（P＜0.05）. 结论 糖尿病大鼠肾脏PEDF、TSP-1异常表达参与DN发生发展,给予Ang-1可改善糖尿病大鼠肾脏PEDF、TSP-1异常表达.     

Rosiglitazone protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression

In this study, the effects of rosiglitazone on renal matrix metalloproteinase-9 (MMP-9) expression and its possible renoprotective mechanisms were investigated in streptozotocin-induced diabetic rats. We examined the urinary excretion rates of albumin (ALB), retinal-binding protein (RBP) and MMP-9 in control healthy rats (group C, n = 8), untreated diabetic rats (group D, n = 8) and diabetic rats treated with rosiglitazone (5mg/kg/day) (group R, n = 8) at eighth week. The renal tissue of diabetic rats was obtained for observing renal pathological changes by electron microscope and examining the expression of renal MMP-9 mRNA by RT-PCR. Our results showed that urinary excretion rates of MMP-9. ALB and RBP were significantly increased concurrently with the expression of renal MMP-9mRNA in group D compared with those of group C. Rosiglitazone significantly reduced urinary excretion rates of ALB, RBP and MMP-9 as well as the expression of renal MMP-9 mRNA. In addition, urinary excretion rate of MMP-9 showed positive relationship with urinary excretion rates of ALB and RBP. In conclusion, rosiglitazone definitely protects diabetic rats against renal injury, which may be partly associated with decreasing expression of renal MMP-9 mRNA and urinary MMP-9 production.     

The timing of dialysis and kidney transplantation in type 1 diabetes

Despite significant improvements in the treatment of diabetic nephropathy over the last 20 years, patients with type 1 diabetes are at high risk of developing end-stage renal disease (ESRD) and high mortality once ESRD develops. The timing of dialysis initiation has occurred earlier over the years, but a recent study has led to a re-evaluation of that approach. People with type 1 diabetes treated with pre-dialysis (pre-emptive) transplantation have a lower death rate than people with type 1 diabetes treated with dialysis. Living donor kidney transplantation is possible before starting dialysis and is associated with better kidney and patient outcomes as compared to transplantation while on dialysis. Multiple barriers remain that prevent people with type 1 diabetes from enjoying the reduced risk of death afforded by a pre-emptive kidney transplant, including lack of knowledge by primary care physicians, endocrinologists and nephrologists, late referral for transplantation, patient and family misconceptions about timing of transplantation and who can be a donor. New data on both the optimal time to initiate dialysis or to pursue transplantation will be reviewed.     

氯沙坦对Nestin在糖尿病大鼠肾组织中表达的影响

目的研究中间丝蛋白Nestin在糖尿病大鼠肾组织中的表达以及血管紧张素Ⅱ受体1拮抗剂(AT1Ra)氯沙坦的影响。方法雄性Wistar大鼠30只,随机分出正常对照组(N组)10只,余20只腹腔注射STZ制备糖尿病大鼠模型。模型制备成功后,再随机分为糖尿病组(DM组)10只和氯沙坦治疗组(DL组)10只。DL组大鼠每日给予氯沙坦20 mg/kg灌胃。干预8 w后,生化方法检测各组大鼠血糖、血尿素氮(BUN)及24 h尿蛋白。电镜观察足细胞超微结构变化;免疫组织化学、流式细胞术、Wertern印迹检测肾组织中Nestin蛋白的表达。结果 DM组大鼠Nestin蛋白表达明显高于N组;氯沙坦治疗后,Nestin表达明显降低。相关性分析显示,Nestin蛋白表达水平与24 h尿蛋白量密切相关(P<0.01)。结论Nestin表达升高可能参与了糖尿病大鼠蛋白尿的发生,氯沙坦对肾脏的保护作用可能部分的是通过降低Nestin的表达而实现的。     

The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney disease

Objective

We have recently shown increased sensitivity to IGF-I induced signal transduction in kidneys of diabetic mice. Accordingly we investigated the effects of PQ401, a novel diarylurea compound that inhibits IGF1R autophosphorylation in type I diabetes.

Methods

Control (C) and Diabetic (D) mice were administered PQ401 (CP, DP) or vehicle (C, D) for 3 weeks.

Results

CP animals showed a decrease in renal phosphorylated (p-)AKT and p-IGF1R. However, PQ401 had no effect on diabetic state (hyperglycemia, weight loss) or renal disease parameters (hypertrophy, hyperfiltration and albuminuria). Type IV collagen as well as TGF-β mRNA increased in DP and D compared to C. In the CP group renal hypertrophy with fat accumulation in proximal tubuli and increased renal IGF-I, collagen IV and TGF-β mRNA were seen.

Conclusions

IGF1R inhibition by PQ401 exerted no significant effects on diabetic kidney disease parameters, arguing against a role for IGF-I in the pathogenesis of diabetic kidney disease. However, PQ401 affects normal kidneys, inducing renal hypertrophy as well as collagen and fat accumulation, with increased renal IGF-I mRNA, suggestive of a damage-regeneration process. Therefore, this diarylurea compound is not beneficial in early diabetic kidney disease. Its potential deleterious effects on kidney tissue need to be further investigated.     

Skeletal myoblast based delivery of angiogenic growth factors: a comparison between angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

Introduction Extensive cell death and an associated myocardial dys- function are the common features of chronic heart disease. Given the inadequate ability of the human heart to regenerate, a more recent approach to counter the remodel- ing process is to compensate for the loss of functioning cardiomyocyte number through stem cell transplantation with angiomyogenic potential.1,2 The novel approach of heart cell therapy is to repopulate the scar tissue with myogenic cells that may be functional…     

Effects of indomethacin on kidney function in Type 1 (insulin-dependent) diabetic patients with nephropathy

Summary We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albumimiria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E₂ (253pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95pg/min) and 11 non-diabetic women (132 pg/min), respectively (p<0.01). Glomerular filtration rate (single bolus ⁵¹Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized doubleblind trial, with the patients receiving either indomethacin (150mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E₂ excretion (73%, p<0.01), glomerular filtration rate diminished from 120±18 to 106±17ml/min/1.73m² (p<0.05), albuminuria declined from 148 to 69 g/min (median and range) (p<0.05) and fractional clearance of albumin diminished 42% (p<0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4±4 versus 14.2±3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.     

糖尿病大鼠肾脏细胞凋亡与Bax和Bcl-2基因表达

目的　观察糖尿病大鼠肾脏细胞凋亡、Bax和 Bcl- 2表达及二者的相关性。　方法　单侧肾切除大鼠腹腔注射链脲佐菌素诱发糖尿病 ,采用原位末端标记法检测肾脏细胞凋亡 ;流式细胞术和免疫组化检测肾皮质 Bax和 Bcl- 2表达水平 ;原位杂交检测 Bax和 Bcl- 2 m RNA表达 ,并观察尿蛋白、BU N、尿肌酐等反映肾功能的有关指标。　结果　在制模后 2、4、8、12周时 ,糖尿病组大鼠较对照组肾小球、肾小管凋亡细胞数明显增多 ,Bax、Bcl- 2蛋白和 m RNA的表达显著增强 (P<0 .0 5 )。随着大鼠糖尿病病程延长 ,肾功能恶化 ,肾脏凋亡细胞数逐渐增多 ,Bax表达亦逐渐增强 ,Bax/Bcl- 2比增加 ,且肾脏凋亡细胞数与 Bax及 Bax/Bcl- 2比具有相关性 (P<0 .0 5 )。　结论　肾脏凋亡细胞的不断增加可能是糖尿病肾病发生、发展的原因之一 ,Bax和 Bcl- 2可能参与肾脏细胞凋亡的调控。