野菊花提取物对糖尿病肾病大鼠的影响及作用机制

目的 观察野菊花提取物对糖尿病肾病大鼠的影响及作用机制。方法 将48只SD大鼠,♀,随机分为正常对照组、模型对照组和野菊花低、中、高剂量组和阳性药依帕司他组(n=8)。除正常对照组外,其余各组大鼠腹腔注射链脲佐菌素35 mg·kg^-1,成功造模后野菊花组分别给予1,2,4 g·kg^-1野菊花提取物,依帕司他组给予10 mg·kg^-1依帕司他,连续灌胃8周后,检测大鼠血糖、体质量、肾脏脏体比、24 h尿白蛋白量、肾组织超氧化歧化酶(SOD)、过氧化氢酶(CAT)的活性及丙二醛(MDA)的含量;HE染色检测肾脏病理改变,ELISA法检测醛糖还原酶(AR)活性并测定其基因表达。结果 与正常对照组相比,模型对照组上述指标除CAT外均有显著改变;与模型对照组相比,野菊花能明显降低大鼠血糖水平、AR活性及其基因表达,明显减少24 h尿白蛋白,升高肾组织SOD、CAT活性,显著降低MDA含量。结论 野菊花提取物对大鼠糖尿病肾病有一定治疗作用,在调节血糖的同时,可能通过提高机体抗氧化能力、减少肾脏AR活性与基因表达以抑制多元醇通路的激活发挥其肾功能的保护作用。     

基质金属蛋白酶及其抑制因子与糖尿病肾病研究进展

糖尿病肾病 (DN)的病理学特征包括肾小球系膜区无细胞性增宽和肾小球基底膜弥漫性增厚 ,这种变化的组织学基础即是细胞外基质 (ECM)积聚。正常情况下 ,ECM产生和降解的动态平衡处于机体的精确调控下。越来越多的证据表明 ,由于各种代谢和血流动力学因素致ECM生成增加和 (或 )降解减少 ,是DN发生发展的重要原因。糖尿病时ECM增多的机制已有较多且深入的研究 ,而对ECM降解机制却知之甚少。近年来 ,有关ECM降解的主要酶系———基质金属蛋白酶(MMPs)及其特异性抑制剂———基质金属蛋白酶组织抑制因子 (TIMPs)的研究为探索DN的发…     

基质金属蛋白酶、纤溶酶与糖尿病肾病

糖尿病肾病 (ＤＮ)的基本病变是肾小球基底膜增厚和细胞外基质 (ＥＣＭ)增多 ,基质代谢异常在其中起了重要作用。高糖状态下转化生长因子 β(ＴＧＦ β)高表达引起ＥＣＭ合成增多 ,已为国内外学者所公认 ,而ＥＣＭ降解机制的研究只是近些年才被重视。与基质降解有关的酶包括基质金属蛋白酶 (ｍａｔｒｉｘｍａｔａｌｌｏ ｐｒｏｔｅｉｎａｓｅｓ ,ＭＭＰｓ)、纤溶酶 (ｐｌａｓｍｉｎ)、半胱氨酸蛋白酶、天冬氨酸蛋白酶四种 ,但起作用的主要是前两种 ,本文以ＭＭＰｓ为主综述如下。1　ＭＭＰｓ1.1　ＭＭＰｓ的生物学特性　ＭＭＰｓ属于Ｚｎ2 +…     

醛糖还原酶5’端两种基因多态性与2型糖尿病肾病的相关性研究

目的探讨醛糖还原酶(AR)基因启动子区C(-106)T单核苷酸多态性和2.1Kb处(AC)n二核苷酸微卫星多态性与2型糖尿病肾病(DN)的关系。方法用聚合酶链反应(PCR)、测序及琼脂糖凝胶电泳技术检测AR基因两多态位点的基因型及等位基因,比较各组分布频率。结果在DM组和CON组均发现AR基因C(-106)T多态位点存在C、T两种等位基因和CC、CT、TT三种基因型,(AC)n序列的7种等位基因(Z-6~Z+6);T、Z-2等位基因及CT+TT及含有Z-2的基因型在DN组明显高于NDN和CON组,但在DM组和CON组之间无显著性差异。结论 AR基因C(-106)T多态位点的T等位基因及(AC)n多态位点的Z-2等位基因可能是DN的易感基因。     

明胶酶和糖尿病肾病

明胶酶是基质金属蛋白酶中的重要一员，其作用底物是血管基底膜和细胞外基质的主要成分，与糖尿病血管并发症关系密切。研究表明，糖尿病肾病可能是在基因易感性基础上，在高糖、糖基化终末产物等代谢紊乱，炎性细胞因子，组溶酶系统失衡等病理因素的作用下，明胶酶的表达和活性发生一系列的变化，细胞外基质合成和降解高度失衡，细胞外基质逐渐积聚，最终导致的糖尿病肾病典型病理改变。     

2型糖尿病肾病患者血浆MMP-2和MMP-9水平检测的临床意义

目的探讨了2型糖尿病肾病患者血浆MMP-2和MMP-9水平的变化及临床意义。方法采用ELISA法测定了42例糖尿病无肾病和33例糖尿病肾病患者血浆MMP-2和MMP-9水平的变化,并与35例正常健康人作比较。结果2型糖尿病肾病患者血浆MMP-2水平非常显著地高于正常人组(P<0.01),而MMP-9水平则显著地低于正常人组(P<0.01),2型糖尿病肾病组与无肾病组亦有显著性差异(P<0.05)。结论2型糖尿病肾病的发生与发展与血浆MMP-2和MMP-9的水平变化密切相关,具有重要的临床价值。     

糖尿病肾病大鼠MMP-9/TIMP-1的表达及钙拮抗剂对其表达的影响

目的观察糖尿病肾病(DN)模型大鼠肾组织MMP-9、TIMP-1的表达状况,以及钙离子拮抗剂硝苯地平对其表达的影响,探讨MMP-9、TIMP-1在DN发生、发展过程中的作用,以及钙离子拮抗剂硝苯地平对肾脏保护作用的机制。方法大鼠随机分为3组:健康对照(N)组、DN组和硝苯地平治疗(T)组,每组10只。采用链脲佐菌素诱发DN大鼠模型,治疗组以硝苯地平控释片15mg(kg·d)干预治疗,治疗2周和4周,检测大鼠平均动脉压(MAP)、尿蛋白量(24h)、Scr水平;RT-PCR检测MMP-9、TIMP-1mRNA的表达。结果与N组比较,DN组大鼠MAP、尿蛋白量、Scr水平均显著上升[分别为(141.1±8.7)比(99.8±3.8)mmHg、(78.87±17.62)比(6.30±1.91)mg/24h、(203.88±18.08)比(84.98±10.09)μmmo/L,P均<0.05];肾组织MMP-9、TIMP-1mRNA表达均显著增强(P<0.05),且MMP-9/TIMP-1的比值明显下降(P<0.05)。与DN组比较,T组MAP[(102.6±4.4)mmHg]、尿蛋白量(24h)[(58.35±10.48)mg]、Scr水平[(165.81±15.86)μmmo/L]均显著下降(P均<0.05);肾组织MMP-9、TIMP-1mRNA表达也显著增强(分别P<0.05和P<0.01),MMP-9/TIMP-1比值显著升高(P<0.05)。结论 DN大鼠肾组织MMP-9及TIMP-1的表达增高,MMP-9/TIMP-1比值下降。硝苯地平可能是通过影响MMP-9及TIMP-1的表达而实现对肾脏的保护作用。     

复方交泰丸对糖尿病大鼠肾损伤的保护作用及其机制的研究

糖尿病肾病是糖尿病的主要微血管并发症,其严重性仅次于心脑血管病。目前研究抗糖尿病肾病的有效方药以控制和延缓糖尿病肾病的发展成为学科领域的热点课题。复方交泰丸可改善糖尿病临床症状,降低血糖,改善血脂及机体抗氧化状态,保护血管内皮功能[1]。本研究进一步观察复方交泰丸对链脲佐菌素诱导的糖尿病大鼠肾损伤的保护作用,并从肾组织氧化应激、一氧化氮水平和醛糖还原酶(AR)活性及基因表达的变化等方面探讨其可能的作用机制,为临床应用提供实验依据。1材料与方法1.1材料复方交泰丸由中山大学药学院提取制成干粉颗粒(批号:0504011);消…     

糖尿病肾病患者血清MMP-2、MMP-9水平与血管钙化的关系

目的探讨糖尿病肾病患者血清基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)水平与血管钙化的关系。方法收治的糖尿病肾病患者178例,分为糖尿病肾病未钙化组92例、糖尿病肾病钙化组86例,同期选择门诊正常体检者87例为对照组,测定3组血肮酐(Scr)、血磷(P³⁺)、血钙(Ca²⁺)、MMP-2、MMP-9、甲状旁腺激素(PTH)、碱性磷酸酶(ALP)、超敏C-反应蛋白(hs-CRP)水平。结果糖尿病肾病钙化组MMP-2水平高于糖尿病肾病未钙化组和对照组,糖尿病肾病未钙化组MMP-2水平高于对照组;糖尿病肾病钙化组MMP-9水平低于糖尿病肾病未钙化组和对照组,糖尿病肾病未钙化组MMP-9水平低于对照组,差异均有统计学意义(P<0.05);糖尿病肾病钙化组Scr、P³⁺、Ca²⁺、PTH、ALP、hs-CRP水平高于糖尿病肾病未钙化组和对照组,糖尿病肾病未钙化组Scr、P³⁺、Ca²⁺、PTH、ALP、hs-CRP水平高于对照组,差异有统...     

黄连素对糖尿病肾损伤大鼠肾功能、氧化应激、肾脏醛糖还原酶的影响

目的观察黄连素对链脲佐菌素诱导的糖尿病肾损伤大鼠肾功能保护作用,并从抗氧化应激、抑制肾脏醛糖还原酶活性及其基因表达等方面探讨黄连素抗糖尿病大鼠肾损伤的作用机制。方法用腹腔注射链脲佐菌素方法复制糖尿病大鼠肾损伤模型。随机分为正常对照组、模型对照组、黄连素组,每组10只。黄连素经口灌胃200 mg.kg-1.d-1,每周给药6 d,共12 wk。比较各组大鼠血糖、肾脏肥大指数(肾重/体重)、尿素氮(BUN)、血肌酐(Cr)、24h尿蛋白(UP24)等肾功能相关指标,比较各组血清超氧化物歧化酶(SOD)活性、脂质过氧化代谢产物丙二醛(MDA)含量、肾组织醛糖还原酶(AR)活性及其基因表达的改变。结果模型组大鼠血糖维持在较高水平、肾脏肥大指数、BUN、Cr、UP24等较正常组明显升高(P<0.05),血清SOD活性低下,MDA含量增加(P<0.05),肾脏AR活性与其基因表达明显升高(P<0.05)。黄连素组与模型组相比,能明显降低血糖、有效控制体重下降、明显改善肾脏肥大指数、BUN、Cr、UP24等指标(P<0.05),血清SOD活性增强,同时MDA含量减少(P<0.05),肾脏AR活性降低及AR mRNA水平下调(P<0.05)。结论对糖尿病肾损伤大鼠,黄连素在调节血糖的同时,可能通过提高机体抗氧化能力、减少肾脏AR活性与基因表达以抑制多元醇通路的激活发挥其肾功能的保护作用。     

Emerging drugs for diabetic nephropathy

There is an increasing number of patients with diabetes mellitus in many countries. Diabetic kidney disease, one of its microvascular complications, is also increasing markedly and has become a major cause of end stage renal disease worldwide. Intervention for preventing and delaying the development and progression of diabetic kidney disease is not only a medical concern, but also a social issue. Despite extensive efforts, however, medical interventions thus far are not effective enough to prevent the progression of the disease and the development of end stage renal disease. This justifies attempts to develop novel therapeutic approaches for diabetic nephropathy. Recent insights on its pathogenesis and progression have suggested new targets for the specific treatment of this disease. They include aldosterone, aldose reductase, arachidonic acid metabolites, growth factors, advanced glycosylation end-products, peroxisome proliferator-activated receptors and endothelin. Several other biochemical mediators have been targeted in experimental animal models with the goal to prevent diabetic nephropathy progression, but translation to clinics of these experimental achievements are still limited or lacking.     

EGCG对实验性糖尿病大鼠肾脏的保护作用

目的观察表没食子儿茶素没食子酸酯(EGCG)对大鼠糖尿病肾脏的保护作用。方法采用链脲佐菌素(65 mg.kg-1)腹腔注射建立糖尿病大鼠模型,实验分4组:对照组、模型组、EGCG治疗组Ⅰ和治疗组Ⅱ,后两组于模型成功后1 wk和4 wk给予EGCG 5 mg.kg-1.d-1腹腔注射。分别测定各组4、8、12 wk时尿白蛋白/肌酐比值(A/C)。12 wk后,采用高效液相测定血浆同型半胱氨酸(tHcy)含量;观察肾脏损伤后病理形态学变化;应用免疫组化检测肾组织细胞外基质蛋白酶-9(MMP-9)的表达;生化分析肾脏氧化应激状态。结果模型组与对照组相比:大鼠肾重/体重明显升高;肾小球肥大,细胞增生,PAS阳性物质明显沉积;血浆tHcy含量及肾组织MMP-9的表达明显增加。经EGCG干预后大鼠生化指标和肾重/体重明显改善;肾脏的抗氧化能力增强和氧化应激降低;血浆tHcy含量下降和MMP-9的表达减弱。EGCG两治疗组相比较,其结果也存在差异。模型组大鼠尿A/C在不同时相点都维持在高水平,且随着时间的延长而逐渐升高,EGCG治疗组I在各时间点与模型组相比A/C明显降低(P<0.01),而治疗组Ⅱ在12 wk时明显低于模型组(P<0.05),在不同时间点治疗组I和治疗组Ⅱ之间存在差异。结论EGCG对糖尿病肾病具有保护作用,其作用机制可能是通过提高机体抗氧化应激能力,降低血浆tHcy含量,抑制肾组织MMP-9表达而减少糖尿病肾病损害。     

依帕司他对糖尿病大鼠肾脏醛糖还原酶活性、细胞凋亡及超微结构的影响

目的:研究醛糖还原酶(AR)、凋亡相关蛋白Bcl-2和Bax与糖尿病肾病的关系,探讨醛糖还原酶抑制剂(ARIs)依帕司他对糖尿病肾病的治疗作用。方法:雄性Wistar大鼠30只,随机平均分为3组:正常对照组、糖尿病模型组和依帕司他(10 mg.kg-1.d-1)治疗组,模型组和依帕司他组腹腔注射链脲佐菌素65 mg.kg-1诱发糖尿病。16周后,处死大鼠,分离晶体和肾脏,测定组织AR活性,观察Bcl-2和Bax的表达,取部分肾皮质电镜细胞计量、观察细胞凋亡的形态学变化。结果:与正常对照组相比,糖尿病模型组肾脏皮质AR活性明显升高(P<0.01),依帕司他治疗组AR活性明显较模型组降低(P<0.01),而血糖无明显变化。糖尿病模型组肾脏Bcl-2和Bax蛋白表达增加,依帕司他治疗组的Bcl-2蛋白表达较模型组增多,而Bax蛋白表达较模型组减少。透射电镜下见糖尿病模型组肾脏肾小管上皮细胞呈典型的凋亡形态学改变,依帕司他治疗组大鼠肾组织细胞凋亡改变明显减轻。糖尿病模型组肾小球基底膜增厚,系膜区域扩大,治疗组病变减轻。结论:AR过度激活可能通过促进Bcl-2和Bax蛋白的表达诱导细胞凋亡,而参与DN的发生与发展。依帕司他通过抑制醛糖还原酶活性,调节Bax和Bcl-2的表达抑制细胞凋亡,改善糖尿病大鼠肾脏结构与功能。     

Anti‐oxidative effect of the β‐blocker carvedilol on diabetic nephropathy in non‐obese type 2 diabetic rats

Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The β‐blocker carvedilol has been proven to have an anti‐oxidant property. The aim of the present study was to elucidate the effects of carvedilol on diabetic nephropathy. At 20 weeks of age, male Spontaneously Diabetic Torii (SDT) rats were divided into three groups based on treatment: (i) an INS group (administered insulin); (ii) a CAR group (administered 10 mg/kg per day, p.o., carvedilol); and (iii) a diabetic (DM) group (administered vehicle). Rats were treated for a period of 10 weeks and were killed at 30 weeks of age. Urinary albumin excretion, renal histomorphology, and oxidative stress were evaluated. Urinary albumin excretion was significantly lower in the CAR than DM group (42.82 ± 3.94 vs 76.62 ± 13.74 mg/day respectively; P < 0.05). The mesangial index was lower in the CAR group than in the DM group. Urinary excretion of 8‐hydroxydeoxyguanosine (8‐OHdG), the number of 8‐OHdG‐positive cells in glomeruli, and the mRNA expression of NADPH oxidase p22^phox and p47^phox were also lower in the CAR than DM group. However, haemoglobin A1c (HbA1c) and blood pressure levels were comparable between the two groups. The results suggest that carvedilol could prevent the progression of diabetic nephropathy by suppressing oxidative stress.     

环孢素A对糖尿病肾病大鼠足细胞氧化应激损伤的作用研究

目的 通过构建糖尿病肾病(DN)大鼠模型,研究环孢素A对DN大鼠足细胞氧化应激损伤的影响.方法 将30只SPF级SD大鼠随机分为对照组、模型组和环孢素A组,每组10只.通过高糖高脂饲料联合链脲佐菌素(STZ)建造大鼠DN大鼠模型(ip 40 mg/kg 1％链脲佐菌素).建模4周后,环孢素A组大鼠ig 3 mg/kg环...     

Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats

Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.     

Protective effects of bendazac lysine on early experimental diabetic nephropathy in rats

Aim: To investigate the preventive and protective effects of bendazac lysine (BDL) on experimental early diabetic nephropathy (DN) rats. Methods: After an early DN model was induced by streptozotocin, rats were administered BDL at doses of 100, 200, and 400 mg/kg for 8 weeks. Blood glucose, microalbuminuria,kidney index, total antioxidative capacity, laminin, advanced glycation end products (AGE), aldose reductase (AR) activity, and the relative quantity of transforming growth factor β1 (TGF-β1) mRNA were measured by different methods.The ultrastructural morphology was observed by transmission electron microscope. Results: The physical behaviors of early DN rats were hypopraxia,cachexia, and polyuria, while those treated with high doses of BDL were vibrant and vigorous. For BDL-treated DN rats, when compared with vehicle-treated DN rats, the blood glucose level and the intensity of oxidative stress were ameliorated.Also, the microalbuminuria level, AGE either in serum or in renal, and AR activity were significantly reduced. Furthermore, the expression of TGF-β1 mRNA in the kidney cortex was declined and the thickness of glomerular base membrane was decreased significantly. The ultrastructure of glomerulus and mesangial matrix of BDL-treated DN rats were ameliorated. Conclusion: BDL has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.     

福辛普利联合依帕司他片治疗糖尿病肾病的疗效观察

目的 研究福辛普利联合依帕司他片治疗糖尿病肾病的疗效。方法 选择2016年1月-2017年12月新疆喀什第三师医院收治的60例糖尿病肾病患者,随机分为两组。对照组口服依帕司他片治疗,每次50 mg,每天3次。观察组联合口服福辛普利钠片,每次20 mg,每天1次。两组均治疗4周。比较两组的疗效以及治疗前后的肾功能、氧化应激指标改变情况。结果 观察组的有效率为86.67%,显著高于对照组的70.00%（P<0.05）。治疗后,两组患者的尿素氮（BUN）、24 h尿蛋白和血肌酐（Scr）均较治疗前显著降低（P<0.05）,且观察组显著低于对照组（P<0.05）。治疗后两组的丙二醛（MDA）值较治疗前显著降低（P<0.05）,总抗氧化能力（T-AOC）和超氧化物歧化酶（SOD）水平均较治疗前显著升高（P<0.05）,且观察组显著优于对照组（P<0.05）。结论 福辛普利联合依帕司他片在减少糖尿病肾病患者全身氧化应激、改善肾功能方面均具有积极作用,可显著提高疗效,值得应用推广。