糖尿病肾病的病理表现

糖尿病肾病 ,又称糖尿病肾小球硬化症 ,为糖尿病的常见微血管并发症 ,1型及 2型糖尿病均可发生。该病主要病变在肾小球及肾脏微动脉 ,肾小球出现以细胞外基质增多为主要特征的的病理表现 ,下面作一详述。1　肉眼大体观察从肾小球高滤过期 (Ｍｏｇｅｎｓｅｎ糖尿病肾损害分期的Ⅰ期 )直至临床糖尿病肾病期 (糖尿病肾损害Ⅳ期) ,糖尿病患者肾脏体积常逐渐增大 ,可增大 >2 0 % ,肾脏体重也随之增加。即使糖尿病肾损害已进展至慢性肾功能不全早期 ,部分患者肾脏体积仍大于正常。2　光学显微镜检查2 .1肾小球病变　糖尿病肾损害Ⅰ期时做病理检查 …     

胰岛素对初发糖尿病大鼠肾小球山梨醇代谢变化的影响

探讨胰岛素对肾小球内山梨醇代谢变化的影响，以进一步证实山梨醇代谢变化的发生机理，采用高压气相色谱－质量分析的方法，对链脲菌素诱发的４周糖尿病大鼠组，糖尿病大鼠胰岛素组肾小球内葡萄糖，山梨醇，果糖含量进行了检测。     

重视糖尿病肾脏病变的诊断与治疗

林善锬　　糖尿病发病率在我国从７０年代中期的１％上升至近来的近３％。糖尿病肾脏病变在胰岛素依赖性及非胰岛素依赖性糖尿病发病中分别为３０～４０％与１５～２０％左右。在许多国家，糖尿病所致的肾病已是导致慢性肾衰的首因，在我国此趋势在一些血透中心也渐显见。糖尿病肾病（ＤＮ）的过程在早期为肾脏体积过大，肾小球容积过多，以及肾小球滤过率过高；之后肾小球系膜细胞增生，肾小球基质积聚，尿白蛋白排泄增加；最后肾小球硬化，临床上表现为肾功能衰竭。由于早期肾脏病有关症状不多，在少量蛋白尿时也不容易被注意，因此大多数…     

糖尿病患者的肾脏SPECT改变

以＾９９ｍＴｃ－ＤＴＰＡ作示踪剂，应用ＳＰＥＣＴ计算机系统对８７例糖尿病患者进行肾动态显像及肾小球滤过率测定，其异常率为６１％。其中半排泄率≥５０％是较敏感的异常指标。肾小球滤过率改变与传统的肾损害分期法基本一致，但有较大交叉，说明此种检查仍然是糖尿病肾病最可靠的判断方法。     

胰腺移植后糖尿病肾病性损害的逆转

糖尿病肾病是晚期肾病的最重要原因。糖尿病肾病的发生是由于细胞外基质逐渐蓄积在肾小球和肾小管基底膜、肾小球膜及间质组织，以及出现肾小球小动脉透明变性和肾小球整体硬化所致，高血糖是其先决条件。研究发现，未接受肾移植的无尿毒症Ⅰ型糖尿病病人在胰腺移植后5年的期间内并未能使已形成的糖尿病肾病损害改变。但胰腺移植后血糖长期恢复正常对糖尿病肾病损害是否有影响尚不清楚，为此作者研究了一组胰腺移植后血糖保持正常达10年的病人的肾功能及肾组织学。方法研究对象为8例接受胰腺移植的Ⅰ型糖尿病病人，均有糖尿病肾病性损害，但…     

大黄抑制糖尿病鼠肾肥大和肾小球多肽生长因子表达的关系

本文观察了中药大黄醇提物对糖尿病大鼠肾小球内多肽长生因子的影响。结果表明，糖尿病初期虽还未见肾重量的明显增加，但肾小球内生长用于的表达已显著“上调”，以链脲菌素注射后２４ｈ最明显，大黄治疗后，其多肽生长因子表达显著“下调”，并且在治疗９６ｈ后肾脏重量亦明显低于非治疗组。因此，说明大黄抑制糖尿病大鼠肾脏肥大的作用与其“下调”肾小球内多肽生长因子的表达有关。     

糖尿病肾病患者足细胞病变的临床病理特征

目的：研究2型糖尿病肾病患者肾小球足细胞病变，分析其与血糖控制、蛋白尿、肾功能及肾组织病理形态学改变之间的关系。方法：27例经肾穿刺活检明确诊断的2型糖尿病肾病。肾组织病理定量计数肾小球足细胞数。借助足细胞特定标志物WTl与肾小球基膜Ⅳ型胶原α3链(C—Ⅳα3)双套色荧光染色，用激光共聚焦荧光显微镜对肾小球足细胞进行准确的密度定量分析。结果：糖尿病肾病患者无论临床表现为微量白蛋白尿、蛋白尿(尿蛋白＜3．5g/24h)，还是大量蛋白尿(尿蛋白＞3．5g/24h)，均伴肾小球足细胞数目及密度的减少，其中以大量蛋白尿组最为显著，蛋白尿组次之，微量白蛋白尿组最轻。足细胞数目及其密度与尿蛋白量呈显著负相关(P＜0．01)。足细胞数目的减少还与肾小球病理改变相关，表现为肾小球K—W结节病变者其足细胞数明显少于肾小球弥漫系膜增生性病变者(P＜0．01)。此外，足细胞数减少严重者肾小球硬化以及血清肌酐水平升高的发生率均明显增高。结论：糖尿病肾病患者早期就表现出肾小球足细胞数目及其密度的减少，随着病变加重，这种变化愈发明显。足细胞病变不仅导致大量蛋白尿的发生，而且还与肾小球硬化和肾功能损伤的发生有关。     

Ⅳ型胶原与糖尿病肾病

糖尿病肾病（ＤＮ）是糖尿病（ＤＭ）最常见和最严重的慢性并发症之一，其病理特点是肾基底膜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、肾功能衰竭等。而基底膜和ＥＣＭ由胶原、非胶原糖蛋白和蛋白多糖构成，在胶...     

PDGF与糖尿病肾病

血小板源性生长因子(PDGF)主要通过自分泌、旁分泌及内分泌作用参与糖尿病肾病(DN)的发生、发展。PDGF-BB在糖尿病肾脏局部高表达，与转化生长因子协同促进肾小球系膜细胞增生及细胞外基质的合成，导致糖尿病肾小球硬化的发生，而应用阻止PDGF-BB表达的方法则可有效防止DN的发生。     

肾小球血流动力学改变和糖尿病肾病

本文介绍肾小球血流动力学改变对糖尿病性肾病发生和发展的影响，并较详细地阐述糖尿病时肾小球血流动力学改变的产生机制及有关对策。     

Thickening of glomerular basement membrane in spontaneously diabetic rats

Summary The glomerular basement membrane of spontaneously diabetic rats was investigated by quantitative analysis using electron microscopy, with special reference to the effect of ageing. Constant agerelated increase in the width of basement membrane was ascertained both in diabetic and control rats, and the mean values of basement membrane thickness were always higher in the spontaneously diabetic rats than in normal control rats. Significant thickening of glomerular basement membrane was found in the diabetic rats at 12 weeks of age, while younger diabetic rats had no definite increase. The difference in basement membrane thickness between diabetic and normal control rats became larger with increasing age.     

Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E production in diabetic rats

AIMS: Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E(2) (PGE(2)) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O(2-)) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O(2-) and PGE(2) production in diabetic rats. METHODS: STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O(2-) production, glomerular PGE(2) synthesis and creatinine clearance were examined. RESULTS: Glomerular O(2-) production increased in untreated diabetic rats compared to non-diabetic controls (142.2 +/- 12.4 vs. 65.4 +/- 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O(2-) production (93.7 +/- 6.7 counts/mg protein/min). Glomerular PGE(2) synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE(2) synthesis was reduced and creatinine clearance tended to decrease by the treatment. CONCLUSIONS: Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O(2-) production with subsequent decrease in PGE(2) production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.     

Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat

Summary This study has evaluated the effects of the angiotensin converting enzyme inhibitor Enalapril on glomerular ultrastructure and albuminuria in normotensive and hypertensive diabetic rats. Streptozotocin-diabetes was induced in Wistar Kyoto and spontaneously hypertensive rats. Enalapril was administered in drinking water in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Enalapril therapy prevented an increase in glomerular basement membrane thickness in diabetic normotensive, control hypertensive and diabetic hypertensive rats without any significant effect on fractional mesangial volume. Enalapril decreased albuminuria in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Thus, enalapril retards the development of glomerular basement membrane thickening and albuminuria in the rat, in the presence or absence of hypertension.     

Novel biphenyl compound, VMNS2e, ameliorates streptozotocin-induced diabetic nephropathy in rats

Aim: To study the effect of a new biphenyl synthetic compound showing interactions with the active site of protein tyrosine phosphatase 1B by docking and molecular dynamics, VMNS2e in streptozotocin‐induced diabetic nephropathy in rats with various renal function parameters and renal ultrastructure. Methods: Streptozotocin (55 mg/kg)‐induced diabetic rats were orally treated once daily with VMNS2e (30, 60, and 120 mg/kg) for 8 weeks. The body weight and blood glucose levels of the rats were recorded during the study period. After 8 weeks of treatment creatinine clearance, urinary protein, blood urea nitrogen, urinary albumin excretion rate, and insulin levels were measured. An ultrastructure study of the kidney tissue was performed and the glomerular basement membrane thickness was measured. Results: Eight weeks of VMNS2e treatment significantly reduced the fasting blood glucose level, attenuated elevating blood urea nitrogen levels, and reduced glomerular basement membrane thickness. Conclusion: It is concluded that VMNS2e treatment at 30 and 60 mg/kg, when given for 8 weeks, partly ameliorated early diabetic nephropathy in diabetic rats.     

依那普利对糖尿病大鼠肾脏保护作用的实验研究

目的 研究依那普利对糖尿病大鼠肾脏的保护作用。方法 应用依那普利对糖尿病大鼠进行了１０周治疗,观察了其对糖尿病大鼠肾脏的保护作用。结果 对照组糖尿病大鼠肾小球滤过度,肾血流量,滤过分数及尿白蛋白均较正常对照组明显升高,肾小球基底膜不规则增厚,突触融合。依那普利治疗后糖尿病大鼠ＧＦＲ,ＲＰＦ,ＦＦ及ＵＡ均较糖尿病对照组明显降低,病理学异常不明显。     

Effect of the calcium channel blocker nitrendipine in normotensive and spontaneously hypertensive, diabetic rats on kidney morphology and urinary albumin excretion.

OBJECTIVE: To investigate the effect of nitrendipine on the development of renal changes in experimental diabetes. DESIGN: Streptozotocin (STZ)-induced diabetic normotensive Wistar rats (WIS) and spontaneously hypertensive rats (SHR) were randomly allocated to nitrendipine treatment (250 mg/kg fodder) or placebo treatment for 6 months. METHODS: Blood pressure was assessed by the tail-cuff method, urinary albumin excretion (UAE) was determined, and glomerular basement membrane (GBM) thickness, mesangial volume, and mean glomerular volume (MGV) were estimated by morphometric measurements. RESULTS: In diabetic WIS, nitrendipine significantly reduced UAE after 2 months of treatment (P< 0.05), while no effect was was seen after 4-6 months. In diabetic SHR, no effect on UAE was seen at any time. Nitrendipine was unable to inhibit the renal and glomerular enlargement in diabetic WIS and SHR. Diabetes plus hypertension was associated with significant increase in GBM thickness, while diabetes or hypertension alone showed no significant increase in GBM. Nitrendipine treatment was unable to prevent increased GBM in diabetic SHR. CONCLUSION: Nitrendipine inhibits an early increase in UAE in normotensive, diabetic rats, but fails to sustain this effect in long-term diabetes. No effect of nitrendipine was observed in SHR.     

Pathogenesis of diabetic glomerulopathy: hemodynamic considerations

Early stages of diabetes mellitus are characterized by glomerular hyperfiltration in humans and experimental animals. In diabetic rats, single nephron hyperfiltration results from elevations in the glomerular capillary plasma flow rate and hydraulic pressure, which are in turn associated with progressive albuminuria and morphologic injury. Interventions that ameliorate these hemodynamic adaptations afford protection against structural injury. Dietary protein restriction, which lowers glomerular filtration, perfusion, and hydraulic pressure, retards glomerular injury and limits capillary basement membrane thickening in both the glomerular and retinal circulatory beds. Alternatively, selective control of glomerular capillary hypertension using angiotensin I converting enzyme inhibitor therapy limits glomerular injury in this model as well. Each of these interventions is effective even in the absence of improved metabolic control, implying that hemodynamic factors per se are important in this pathogenic process. The pathophysiologic mechanisms of diabetic hyperfiltration remain incompletely elucidated. Recent studies invoke a potential role for atrial natriuretic peptide (ANP). Strict metabolic control abolishes the elevations of glomerular filtration rate and of plasma ANP levels in moderately hyperglycemic diabetic rats. Moreover, infusion of a specific ANP antibody reverses hyperfiltration in diabetic rats. Thus, hyperglycemia-induced chronic volume expansion may trigger ANP release, which in turn contributes to diabetic hyperfiltration. Hemodynamic factors may play an important role in the pathogenesis of extrarenal microangiopathy as well. Elevated peripheral capillary blood flows and/or hydraulic pressure may be found in many peripheral capillaries, in association with thickening of the capillary basement membrane. Dietary protein restriction, which lowers blood flow to many organs, limits retinal as well as glomerular basement membrane thickening in diabetic rats, suggesting that hemodynamically mediated structural injury is a diffuse phenomenon in the diabetic state.     

大黄对糖尿病大鼠肾组织非酶促糖基化的影响

研究了大黄醇提物对糖尿病大鼠肾组织非酶促糖基化的影响。结果表明，Ｒ能减轻ＤＭ大鼠肾脏肥大，使肾重／体得值明显下降，降低ＤＭ大鼠血肌酐和尿素氮水平，使ＤＭ大鼠血糖，果糖胺和糖化珠蛋白含量明显下降。     

低分子肝素对糖尿病大鼠肾脏病变的影响

目的研究低分子肝素对糖尿病大鼠肾脏病变的保护作用及其机制。方法观察低分子肝素对肾小球功能、形态及肾小球基底膜超微结构的影响。结果（１）在病程不同时期（４、８、１２、１６周）治疗组尿白蛋白明显低于非治疗组（Ｐ＜０．０５）；（２）１６周时，光镜及电镜下治疗组肾小球系膜增生、基底膜增厚和足突融合等病变较非治疗组明显减轻，而两组血糖、肾小球平均截面积、肾小球平均体积、肾小球滤过率及血压无明显差异（Ｐ＞０．０５）。结论低分子肝素对糖尿病大鼠的肾脏病变具有一定防治作用，其机制可能不是通过改善血糖及血液动力学实现的。     

Glomerular basement membrane thickening in streptozotocin diabetic rats despite treatment with an aldose reductase inhibitor

This study concerns the possible prevention of glomerular basement membrane thickening in experimental diabetes by an aldose reductase inhibitor (ARI), Statil^®. ARI added to the chow was given to streptozotocin diabetic rats over a period of 6 months. Reference groups were control rats and diabetic rats on the same chow without ARI. The diabetic rats were given insulin two or three times a week, and blood glucose was measured monthly before insulin injections. There was a marked difference in the occurrence of cataracts between the two diabetic groups. ARI treated rats tended to have lower blood glucose than the diabetic reference group, but the difference was not significant. At the termination of the experiment, the left kidney was perfusion fixed, weighed, and prepared for light and electron microscopy. Systematic random sampling from the entire kidney was performed to obtain light microscopic visual fields and ultrathin sections from two glomeruli. Mean glomerular volume was estimated by light microscopy, and glomerular basement membrane thickness, by electron microscopy. Basement membrane thickness was significantly increased in untreated diabetic rats (174 nm, SD = 4.5 nm) as compared to that of controls (Mean: 154 nm, SD = 11.0 nm), and was even more so in ARI treated rats (187 nm, SD = 18.7 nm,) although the ARI treated rats showed less renal and glomerular hypertrophy than did untreated diabetic rats. In conclusion, the ARI treatment over an experimental period of 6 months attenuated diabetic renal and glomerular hypertrophy, but had no effect at all on diabetic glomerular basement membrane thickening.