糖尿病肾病小鼠模型的研究进展

近年来,糖尿病肾病（diabetic nephropathy,DN）已成为导致终末期肾病的主要原因之一。我国2010年进行的流行病学调查显示：20岁以上人群DM患病率已达9.7%,DM前期患病率高达15.5%。DN临床标本的稀缺性突出了DN动物模型的重要。良好的动物模型对DN发病机制的研究和治疗药物的研发至关重要。     

阿霉素肾病动物模型的国外研究进展

阿霉素。肾病动物模型于20世纪80年代初期由国外文献报道，是目前公认的能较好模拟人类慢性肾脏病的动物模型，在肾脏病研究领域已广泛应用。根据其建立方法和病理表现，可分为急性模型和慢性模型，急性模型类似于人类微小病变型肾病（MCN），而慢性模型类似于人类局灶节段性肾小球硬化（FSGS）。阿霉素肾病动物模型的建立与所选动物品系，     

糖尿病肾病研究进展

糖尿病肾病是糖尿病最严重的微血管并发症。近10年来,糖尿病肾病患者快速增长,已成为危害人类健康的公共卫生疾病。目前在欧美等发达国家,DN约占终末期肾病(ESRD)的50%,已成为尿毒症的首位原发病;在我国约占25%～40%,是患者血液透析的重要原因。因此,及时发现与防治DN,对于延缓病情进展、提高患者生活质量意义重大。     

特发性膜性肾病动物模型的研究进展

正膜性肾病(membranous nephropathy,MN)是临床上常见的成人肾病综合征病理类型之一,其病理特征为肾小球基底膜(glomerular basement membrane,GBM)上皮下免疫复合物的沉积,分为特发性膜性肾病(Idiopathic membranous nephropathy,IMN)和继发性膜性肾病(secondary membranounephropathy,SMN)。     

小鼠前列腺癌原位移植动物模型的研究进展

前列腺癌是现阶段泌尿外科临床和基础研究的热点之一.理想的前列腺癌动物模型是进行该项研究的重要工具,小鼠前列腺癌原位移植动物模型是目前应用最广泛的前列腺癌动物模型之一.本文系统回顾了小鼠前列腺癌原位移植动物模型的分类,各类模型的建立方法、特点,模型评价方法及进展情况.     

糖尿病肾病诊断学研究进展

糖尿病肾病（diabetic nephropathy，DN）是糖尿病（diabetes mdlius，DM）最主要的微血管并发症之一，也是导致慢性肾衰竭的主要原因之一。DM可由多种途径损害肾脏，并累及肾脏的所有结构，从肾小球、肾血管到肾小管和肾间质。随着人口老龄化，各国经济的发展和人们生活方式的改变，糖尿病已经成为世界范围内的常见病多发病。因此，DN的患病率在世界范围内迅速增长。     

糖尿病肾病流行病学研究进展

随着人均寿命的延长和生活习惯的改变,如营养过剩、高脂饮食、运动减少及生活节奏加快等,糖尿病（diabetes mellitus,DM）的发病率呈上升趋势,随之糖尿病肾病（diabetic kidney disease,DKD）的发病率也在上升。DKD是DM最常见的微血管并发症,其典型特征是尿白蛋白排泄率的逐渐增加,常常发展至临床蛋白尿,     

糖尿病肾病若干研究进展

糖尿病肾病是微血管病变之一,是糖尿病死亡的主要原因。Davidson报告在1922年发现胰岛素以前,糖尿病患者死于糖尿病昏迷者占42～62％;死于糖尿病微血管病者占18～25％。胰岛素应用临床后,糖尿病昏迷病死率逐渐下降,微血管病病死率显著上升,最近统计前者为1％,后者为75％。又报告胰岛素依赖型糖尿病(首称IDDM)患者死亡原因分别为尿毒症80％,心肌梗塞10％;其它原因10％。IDDM约有30～35％并发糖尿病肾病,有50％IDDM儿童发病后平均20年内发生肾功能衰竭。据估计死     

糖尿病肾病机制的研究进展

2型糖尿病（type2diabetes，T2D）是最常见的内分泌代谢病，而糖尿病肾病（diabeticnephropa—thy，DN）是糖尿病患者最主要的微血管病变之一。     

Myofibroblasts and the progression of diabetic nephropathy

Background. The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.Subjects and methods. We have studied by immunohistochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; &agr;-smooth-muscle actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue for three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression renal cytoskeletal proteins. Results. In normal kidneys, cells expressing &agr;-SMA were confined to the vascular media and adventia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing &agr;-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial &agr;-SMA proved to be a predictor of progressive diabetic nephropathy (R² for 1/serum Cr slope=0.608, P=0.00001). This predictive parameters; tubular atrophy (R²=0.477, P=0.00004) and interstitial fibrosis (R²=0.28, P=0.001). Conclusion. We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.     

Intrarenal dopamine inhibits progression of diabetic nephropathy

The kidney has a local intrarenal dopaminergic system, and in the kidney, dopamine modulates renal hemodynamics, inhibits salt and fluid reabsorption, antagonizes the renin-angiotensin system, and inhibits oxidative stress. The current study examined the effects of alterations in the intrarenal dopaminergic system on kidney structure and function in models of type 1 diabetes. We studied catechol-O-methyl-transferase (COMT)(-/-) mice, which have increased renal dopamine production due to decreased dopamine metabolism, and renal transplantation was used to determine whether the effects seen with COMT deficiency were kidney-specific. To determine the effects of selective inhibition of intrarenal dopamine production, we used mice with proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC(-/-)). Compared with wild-type diabetic mice, COMT(-/-) mice had decreased hyperfiltration, decreased macula densa cyclooxygenase-2 expression, decreased albuminuria, decreased glomerulopathy, and inhibition of expression of markers of inflammation, oxidative stress, and fibrosis. These differences were also seen in diabetic mice with a transplanted kidney from COMT(-/-) mice. In contrast, diabetic ptAADC(-/-) mice had increased nephropathy. Our study demonstrates an important role of the intrarenal dopaminergic system to modulate the development and progression of diabetic kidney injury and indicate that the decreased renal dopamine production may have important consequences in the underlying pathogenesis of diabetic nephropathy.     

Inflammatory stress exacerbates the progression of diabetic nephropathy

Objective To investigate the effects of inflammatory stress on the progression of diabetic nephropathy （DN） through making an inflamed animal model of DN. Methods Male db/db mice and db/m mice were randomly divided into four groups: db/m group (control, n=8), casein injected db/m (db/m＋casein, n=8), db/db mice (db/db, n=8), and casein injected db/db mice (db/db＋casein, n=8). Chronic inflammation was induced by subcutaneously injection of 0.5 ml 10% casein to db/m＋casein and db/db＋casein group every another day while db/m and db/db mice as the control were injected with 0.5 ml distilled water. Body weight and 24-hour urinary protein were measured every week. The plasma levels of serum amyloid A (SAA) and tumor necrotic factor-α (TNF-α) were detected by enzyme-linked immuno sorbent assay. Renal pathological changes were evaluated by renal pathological staining and electron microscope. Immunohistochemical staining and Western blotting were used to detect the expression of podocyte related specific proteins and inflammatory cytokines. Results The plasma levels of SAA[(13.83±0.29) mg/L vs (1.52±0.19) mg/L, P＜0.05; (13.84±0.28) mg/L vs (1.67±0.58) mg/L, P＜0.05] and TNF-α[(14.23±1.42) ng/L vs (10.70±1.38) ng/L, P＜0.05; (14.54±1.91) ng/L vs (10.88±1.22) ng/L, P＜0.05] were significantly increased in db/m＋casein and db/db＋casein group compared to that in db/m and db/db group respectively. Furthermore, the 24-hour urinary protein in casein injected db/db mice was markedly increased compared with db/db group. There were more significant renal pathological injuries and podocyte damage in casein injected db/db mice compared with db/db mice whereas these were no difference in casein injected db/m mice compared with db/m mice. Conclusion Inflammatory stress plays important roles in accelerating the progression of DN.     

Tranilast slows the progression of advanced diabetic nephropathy

BACKGROUND: Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, suppresses collagen synthesis by various cells, including macrophages and fibroblasts, by interfering with the actions of transforming growth factor-beta 1. We investigated the effect of tranilast on progression of diabetic nephropathy (DN), since this process is associated with accumulation of collagens in the glomerulus and interstitium. METHODS: Tranilast (100 mg, 3 times daily) was administered to 9 outpatients with advanced DN who were receiving an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist and who exhibited a progressive decline in renal function. The decline in renal function before and during tranilast treatment was evaluated for each patient on the basis of the slope in reciprocal serum creatinine (1/S(Cr)) over time. Urinary type IV collagen (U-IV.C) and protein (U-P) excretions were measured just before commencement of tranilast treatment and every 2 months during the treatment. RESULTS: One male patient dropped out soon after commencement of tranilast treatment due to development of lung cancer, and hemodialysis was introduced in one female patient 6 months after the start of treatment. In the 8 patients who did not drop out, 1/S(Cr) was significantly less steep during tranilast treatment than before treatment (-0.00748 +/- 0.00700 vs. -0.01348 +/- 0.00636 dl/mg/month, respectively; p = 0.0374). U-IV.C and U-P tended to decrease with time, although the decrease was statistically insignificant. CONCLUSIONS: Our data suggest that tranilast treatment may suppress accumulation of collagens in renal tissue and may be therapeutically useful for reducing the progression of advanced DN.