炎症与糖尿病肾病

近年来,炎症反应在糖尿病及其并发症发病机制中的作用引起了人们的广泛关注,研究报道炎症因子及促炎症因子与糖尿病肾病的发生和发展密切相关,并认为糖尿病肾病是一种炎症性疾病,炎症因子的大量产生参与并促进糖尿病肾病的进展。本文重点就炎症因子与糖尿病肾病的关系以及抗炎治疗对糖尿病肾的保护作用进行综述。     

糖尿病肾病易感基因的研究现状

糖尿病肾病(DN)是Ⅰ型和Ⅱ型糖尿病(DM)常见的微血管并发症之一，大量证据表明遗传因素在DN发生发展中起主要决定作用，其发病与基因多态性、基因突变及异常表达等有关，具有广泛的遗传异质性，了解这些信息对于阐明DN的发生发展、诊断及治疗等有非常重要的意义。     

糖尿病肾病防治新观点--美国第84届内分泌协会年会专题小结

糖尿病肾病是导致糖尿病死亡及终末期肾病透析的主要原因之一。在美国第84届内分泌协会年会上报告了一些糖尿病肾病治疗新观点。内容包括：HOPE研究结果；血管紧张素转换酶抑制剂(ACEI)是糖尿病患者心血管甚至是肾功能不全的保护药；ACEI可能能够预防糖尿病；血管紧张素1(AT1)受体阻滞剂(ARB)肾保护作用的证据；糖尿病中血压控制的重要性；ARB改善这些患者充血性心力衰竭及使用ACEI和ARB的临床建议等。本文对此作一综述。     

金属蛋白酶及其抑制物与糖尿病肾病

基质金属蛋白酶（MMPs)和金属蛋白酶组织抑制剂（TIMPs)是细胞外基质（ECM）合成与降解代谢平衡调节中两个重要的酶系，它们的调节在导致糖尿病肾病的发生发展中起重要作用。检测血清MMPs和TIMPs水平变化能早期诊断糖尿病肾病，应用干预措施有利于糖尿病肾病的早期防治。     

糖尿病肾病大鼠肾脏Tensin表达的变化

目的 观察tensin在糖尿病肾病（DN）大鼠肾脏中的表达，探讨其在DN肾小球纤维化中的作用。方法 链脲佐菌素（STZ）诱导大鼠DN，间接免疫荧光组织化学方法观察DN大鼠肾脏tensin的表达。结果 糖尿病肾病大鼠的肾脏tensin表达明显增加（与正常对照组相比P〈0．01，有统计学意义），阳性表达主要位于系膜细胞胞浆内。结论 tensin在糖尿病肾病大鼠系膜细胞中高表达可能参与了糖尿病肾病过程中肾小球纤维化的形成。     

糖尿病肾病易感基因的研究现状

糖尿病肾病 (DN )是 型和 型糖尿病 (DM)常见的微血管并发症之一 ,大量证据表明遗传因素在 DN发生发展中起主要决定作用 ,其发病与基因多态性、基因突变及异常表达等有关 ,具有广泛的遗传异质性 ,了解这些信息对于阐明 DN的发生发展、诊断及治疗等有非常重要的意义     

循证医学及其医学信息资源分布

循证医学是20世纪80年代在国际上迅速发展起来的一种新的临床医学模式。循证医学强调证据及质量是其基础，提倡用可得到最佳证据指导临床实践。文章就循证医学的概念、起源和发展等方面进行阐述，并介绍了循证医学的信息资源分布。     

糖尿病肾病患者的饮食治疗

糖尿病是一种慢性内分泌代谢性疾病，肾病为糖尿病并发症之一，要防止糖尿病肾病进展，饮食治疗是糖尿病肾病防治中一个重要环节。2000年以来，通过对19例糖尿病肾病的饮食治疗，效果较满意，现报告如下。     

糖尿病患者血清PTH,CT水平的变化

目的：了解糖尿病患者血清甲状旁腺素，降钙素的变化。方法：用ＲＩＡ法测定了７１例糖尿病患者血清甲状旁腺素和降钙素含量，并与３５名健康人作对照。结果：并发糖尿病肾病者血清ＰＴＨ，ＣＴ均升高，并随糖尿病肾病的严重程度而增加，且与肌酐浓度呈正相关。结论：糖尿病患者一旦发生糖尿病肾病，就存在血精ＰＴＨ，ＣＴ含量的异常。     

细胞外基质,细胞生长因子与糖尿病性肾病

细胞外基质（ＥＣＭ）及多种细胞生长因子参与糖尿病性肾病的发病机制，这些细胞生长因子从不同的作用环节引起系膜细胞增生、系膜增殖、ＥＣＭ增多，从而导致糖尿病肾病的发生。     

糖尿病肾病患者血清腺苷脱氨酶活性的变化及意义

目的探讨腺苷脱氨酶（ADA）在糖尿病肾病患者血清中的变化及其临床意义。方法对98例2型糖尿病患者（无蛋白尿组30例、微量蛋白尿组35例、大量蛋白尿组33例）和30例健康体检者ADA、胱抑素C（CysC）、白介素6（IL-6）以及C反应蛋白（CRP）进行测定,并对比分析。结果各组糖尿病患者与对照组的ADA、CysC、CRP和IL-6含量差异均有统计学意义（P〈0.01）;微量蛋白尿组的ADA、CysC、CRP和IL-6水平明显高于无蛋白尿组（P〈0.05）;大量蛋白尿组的ADA、CysC、CRP和IL-6水平明显高于微量蛋白尿组（P〈0.05）。ADA分别与CysC、CRP、IL-6成正相关。结论早期联合检测血清ADA及CRP、CysC、IL-6水平变化可以作为评估糖尿病肾病病情和预后的参考指标。     

The effects of angiotensin-II receptor blockers on podocyte damage and glomerular apoptosis in a rat model of experimental streptozotocin-induced diabetic nephropathy

The aim of the study was to determine in a rat model of streptozotocin-induced diabetic nephropathy the expression of: WT-1 (for podocyte loss in the glomerulus), TGF-beta 1 (for tissue damage), caspase-3 and bax (for glomerular apoptosis) and the possible protective effects of an angiotensin II type 1 receptor blocker. Three groups of male Wistar albino rats were used. The first group consisted of non-diabetic control rats. The second group was the untreated diabetic rats. The third group consisted of diabetic rats treated with Irbesartan, which is an angiotensin II receptor antagonist, widely used in treatment for hypertension. Immunohistochemical stainings for TGF-beta 1, bax, caspase-3 and WT-1 were performed. The microalbuminuria levels of the Irbesartan-treated diabetic group were lower than those of the untreated diabetic group (P < 0.01). The immunostaining of TGF-beta 1, bax and caspase-3 was decreased in glomeruli of the Irbesartan-treated diabetic group compared to the untreated diabetic group. WT-1 immunopositive podocyte numbers were found to be significantly lower in the untreated diabetic group than in the other groups (P < 0.01). In the Irbesartan-treated diabetic group, the WT-1 immunopositive cell numbers were higher compared to the untreated diabetic group (P < 0.01). We conclude that the decrease in the number of podocytes is an early marker of diabetic nephropathy, AT1 receptor blocker has renoprotective effects on the regulation of renal hemodynamics and on the control of tissue damage by preventing podocyte loss, which leads to decrease of bax and caspase-3 expressions of apoptosis related proteins, and may prevent glomerular cell apoptosis via angiotensin II.     

Renal ACE2 expression in human kidney disease

Angiotensin-converting enzyme 2 (ACE2) is a recently discovered homologue of angiotensin-converting enzyme (ACE) that is thought to counterbalance ACE. ACE2 cleaves angiotensin I and angiotensin II into the inactive angiotensin 1-9, and the vasodilator and anti-proliferative angiotensin 1-7, respectively. ACE2 is known to be present in human kidney, but no data on renal disease are available to date. Renal biopsies from 58 patients with diverse primary and secondary renal diseases were studied (hypertensive nephropathy n = 5, IgA glomerulopathy n = 8, minimal change nephropathy n = 7, diabetic nephropathy n = 8, focal glomerulosclerosis n = 5, vasculitis n = 7, and membranous glomerulopathy n = 18) in addition to 17 renal transplants and 18 samples from normal renal tissue. Immunohistochemical staining for ACE2 was scored semi-quantitatively. In control kidneys, ACE2 was present in tubular and glomerular epithelium and in vascular smooth muscle cells and the endothelium of interlobular arteries. In all primary and secondary renal diseases, and renal transplants, neo-expression of ACE2 was found in glomerular and peritubular capillary endothelium. There were no differences between the various renal disorders, or between acute and chronic rejection and control transplants. ACE inhibitor treatment did not alter ACE2 expression. In primary and secondary renal disease, and in transplanted kidneys, neo-expression of ACE2 occurs in glomerular and peritubular capillary endothelium. Further studies should elucidate the possible protective mechanisms involved in the de novo expression of ACE2 in renal disease.     

Adenosine deaminase activity in the serum of type 2 diabetic patients

Adenosine deaminase (ADA) is suggested to be an important enzyme for modulating the bioactivity of insulin, but its clinical significance in diabetes mellitus (DM) is not yet characterized. We measured the serum level of ADA in healthy controls (C, n=29) and type 2 diabetic patients (n=42). The mean serum level of ADA in C, and type 2 diabetic patients was 13.04 +/- 3.3 and was 22.2 +/- 4.3 U/L, respectively (P<0.01[corrected] vs. C). ADA levels of patients were significantly correlated with HbA1c (r=0.45, p<0.01). Our findings suggest that ADA may play a role in insulin effect and glycamic control. On the other hand, increased activity of ADA in type 2 DM might be a marker for insulin indication. However, further studies are required for the pathogenic role of elevated ADA activity in type 2 DM.     

血清补体C1q与狼疮肾炎及糖尿病肾病的相关性分析

目的 探讨血清补体C1q在狼疮肾炎与糖尿病肾病中的变化,为临床狼疮肾炎与糖尿病肾病的诊断与鉴别诊断提供理论依据.方法 选取2015年10月至2016年10月我院住院治疗狼疮肾炎患者33例,糖尿病肾病患者57例,同期体检健康人104例作为对照组,分别测定其血清补体C1q水平.结果 狼疮肾炎组血清补体C1q水平明显低于糖尿病肾病组(P=0.00)和对照组(P=0.001);糖尿病肾病组与对照组比较差异无统计学意义.结论 血清补体C1q水平在各组受试者中不同,检测血清补体C1q水平可用于狼疮肾炎与糖尿病肾病的诊断与鉴别诊断.     

胱抑素C、尿微量白蛋白/肌酐比值对早期糖尿病肾病的诊断价值

目的 探讨测定血清胱抑素C（CysC）、尿微量白蛋白/肌酐比值在早期2型糖尿病肾病（DN）中的诊断价值。方法 选取2017年1月~2018年11月北京市门头沟区医院糖尿病患者276例,其中非糖尿病肾病组122例,早期糖尿病肾病组86例,临床糖尿病肾病组68例,同时选择同期健康体检60例设为对照组,应用日立7600全自动生化分析仪测定血清CysC,尿素氮,血肌酐,尿微量白蛋白,尿肌酐数值。结果 临床糖尿病肾病组CysC、尿微量白蛋白/肌酐比值、尿素氮、肌酐比高于其他三组（P＜0.01）;早期糖尿病肾病组CysC、尿微量白蛋白/肌酐比值分别高于非糖尿病肾病组和对照组（P＜0.01）,其尿素氮、肌酐与非糖尿病肾病组和对照组比较,差异无统计学意义（P＞0.05）;非糖尿病肾病组CysC、尿微量白蛋白/肌酐比值、尿素氮、肌酐与对照组比较,差异无统计学意义（P＞0.05）。结论 CysC、尿微量白蛋白/肌酐比值的测定对早期发现糖尿病肾病有明显的临床价值,而且病情越重,高的越明显;随着病情加重,CysC、尿微量白蛋白/肌酐比值与传统的肾功能指标尿素氮、肌酐相关性明显,而且在糖尿病肾病早期价值明显优于尿素氮、肌酐。     

维持性血液透析患者的动脉粥样硬化

背景：动脉粥样硬化是糖尿病肾病及血液透析患者常见的并发症,维持性血液透析时间长短和其他相关因素对糖尿病肾病患者动脉粥样硬化的影响有待于进一步观察及研究。 目的：观察不同时间维持性血液透析患者的动脉粥样硬化情况,评价血液透析时间及其他相关因素对糖尿病肾病动脉粥样硬化的影响。 方法：利用高频超声检测糖尿病肾病血液透析组、非糖尿病肾病血液透析组、终末期肾病未透析组患者的颈动脉内中膜厚度变化,以健康志愿者作为正常对照组。分析血液透析患者颈动脉内中膜厚度与透析时间的关系,比较各组胰岛素抵抗的变化。 结果与结论：与正常对照组相比,糖尿病肾病血液透析组和非糖尿病肾病血液透析组颈动脉内中膜厚度值增大(P < 0.01);非糖尿病肾病血液透析24个月组颈动脉内中膜厚度值与非糖尿病肾病未透析组差异无显著性意义(P > 0.05);非糖尿病肾病血液透析60个月组颈动脉内中膜厚度值较非糖尿病肾病血液透析24个月组增大(P < 0.05);非糖尿病肾病血液透析60个月组颈动脉内中膜厚度值较终末期肾病未透析组明显增大(P < 0.01)。糖尿病肾病血液透析60个月组与终末期肾病未透析组及糖尿病肾病血液透析24个月组相比,3组间差异无显著性意义(P > 0.05)。糖尿病肾病24个月组HOMA-IR值较糖尿病肾病未透析组稍微降低(P < 0.05),糖尿病肾病60个月组HOMA-IR值较糖尿病肾病未透析组显著降低(P < 0.01)。提示血液透析在一定程度上可以影响糖尿病肾病维持性血液透析患者动脉粥样硬化的进展,且这种作用与透析时间长短有关。     

骨髓间充质干细胞移植改善糖尿病肾病大鼠血糖及尿总蛋白

BACKGROUND: Common strategies for preventing diabetic nephropathy include effective control of blood sugar and blood pressure, inhibition of the rennin-angiotensin system and lipid-lowering therapy, but it is often difficult to get the desired results. OBJECTIVE: To investigate the effect of transplantation of bone marrow mesenchymal stem cells on levels of blood glucose and urinary total protein in diabetic nephropathy rats. METHODS: Forty-five Sprague-Dawley rats were randomly divided into three groups (n=15 per group): normal control group, diabetic nephropathy group and stem cell transplantation group. Rats in the diabetic nephropathy and stem cell transplantation groups were given single use of 60 mg/kg streptozotocin to make diabetic nephropathy models. The same dose of citric acid-sodium citrate buffer was injected in the normal control group. After modeling, 200 μL of bone marrow mesenchymal stem cell solution (2×106) was injected into the left ventricle of rats in the stem cell transplantation group, and then at 7 days after the first transplantation, the cell transplantation was conducted again. The same dose of serum-free L-DMEM was injected intracardially into the rats in the normal control and diabetic nephropathy groups. Levels of urinary total protein and blood glucose were detected.  RESULTS AND CONCLUSION: At 1, 4, 8 weeks after treatment, the urinary total protein and blood glucose levels were significantly higher in the stem cell transplantation group and diabetic nephropathy group than the normal control group (P < 0.05). At 1 week after treatment, the urinary total protein and blood glucose levels were significantly lower in the stem cell transplantation group than the diabetic nephropathy group (P < 0.05). At 4 and 8 weeks after treatment, the total urinary protein and blood glucose levels were slightly higher in the diabetic nephropathy group than the stem cell transplantation group, but there was no significant difference (P > 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation in diabetic nephropathy rats can get good results in a short period, significantly improve the blood glucose and urinary total protein levels, but the long-term treatment effect is poor.      

Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy

Diabetic nephropathy develops in less than half of all patients with diabetes. To study heredity as a possible risk factor for diabetic kidney disease, we examined the concordance rates for diabetic nephropathy in two sets of families in which both probands and siblings had diabetes mellitus. In one set, the probands (n = 11) had no evidence of diabetic nephropathy, with normal creatinine clearance and a urinary albumin excretion rate below 45 mg per day. In the other set, the probands (n = 26) had undergone kidney transplantation because of diabetic nephropathy. Evidence of nephropathy was found in 2 of the 12 diabetic siblings of the probands without nephropathy (17 percent). Of the 29 diabetic siblings of probands with diabetic nephropathy, 24 (83 percent) had evidence of nephropathy (P less than 0.001), including 12 with end-stage renal disease. No significant differences were noted between the sibling groups with respect to the duration of diabetes, blood pressure, glycemic control, or glycosylated hemoglobin levels. Logistic regression analysis found nephropathy in the proband to be the only factor significantly predictive of the renal status of the diabetic sibling. We conclude that diabetic nephropathy occurs in familial clusters. This is consistent with the hypothesis that heredity helps to determine susceptibility to diabetic nephropathy. However, this study cannot rule out the possible influences of environmental factors shared by siblings.