长期抑制大鼠体内内皮衍生舒张因子的生成对其血压及…

本文观察了内皮细胞衍生舒张因子的抑制剂Ｎ＾Ｇ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ ｍｅｔｈｙｌ ｅｓｔｅｒ（Ｌ－ＮＡＭＥ）在抑制大鼠体内ＥＤＲＦ产生后，对其血压和肾功能的影响，结果表明，Ｌ－ＮＡＭＥ治疗４周后，实验组大鼠的平均动脉压显著升高（Ｐ〈０．０１），其肾小球滤过率和肾血流量明显低于正常对照组，肾血管阻力则高于正常对照组；同时、实验组大鼠２４ｈ尿蛋白定量和尿ＮＡＧ酶排出量均明显高于正常组大鼠。     

雌性大鼠增龄性肾病变及转化生长因子—β在肾组织内的表达

目的观察正常雌性大鼠肾脏的增龄性改变以及肾组织内转化生长因子－β（ｔｒａｎｓｆｏｒｍｉｎｇｇｒｏｗｔｈｆａｃｔｏｒ－β，ＴＧＦ－β）及其信使核糖核酸（ｍＲＮＡ）的表达。方法利用光镜、免疫荧光及电镜技术观察了不同鼠龄雌性大鼠的肾组织病理改变及ＴＧＦ－β表达的演变过程，并利用原位杂交技术观察了ＴＧＦ－βｍＲＮＡ在肾组织中的表达情况。结果随着鼠龄的增长，大鼠血尿素氮、肌酐、血脂及尿蛋白定量均无明显变化。１８月龄大鼠的肾小球在光镜下仅见轻度系膜增殖性改变，可见ＩｇＧ、ＩｇＭ在肾小球内沉积，但不伴有Ｃ３的沉积，肾组织内未见有单核巨噬细胞（ＥＤ－１）、Ｔ辅助淋巴细胞（ＣＤ４）及Ｔ抑制淋巴细胞（ＣＤ８）的积聚。电镜下可见肾小球基底膜明显增厚、皱折及结节形成。肾组织免疫荧光及原位杂交技术均证实１８月龄大鼠肾小球内有ＴＧＦ－β表达。结论无蛋白尿的正常雌性大鼠可见明显的肾脏增龄性改变，ＴＧＦ－β在这一病变过程中可能具有重要作用。     

培哚普利对实验性糖尿病大鼠肾脏的保护作用

观察培哚普利（ｐｅｒｉｎｄｏｐｒｉｌ）对链脲霉素诱导的糖尿病（ＤＭ）大鼠肾脏的保护作用。ＤＭ对照组（ＤＣ组）每日注射长效胰岛素，ＤＭ治疗组（ＤＰ组）并每天给予培哚普利１ｍｇ／ｋｇ。于病程１、３、６个月测２４小时尿蛋白。取肾脏作光镜和电镜检查，测定肾小球平均截面积（ＭＧＰＡ）和肾小球平均体积（ＭＧＶ）。结果显示６个月期间ＤＣ、ＤＰ组尿蛋白定量明显高于ＮＣ组（Ｐ＜０．０１），且ＤＣ组高于ＤＰ组（Ｐ＜０．０５）。３、６个月时ＤＣ、ＤＰ组ＭＧＰＡ、ＭＧＶ均大于ＮＣ组，６个月时ＤＰ组小于ＤＣ组。电镜观察表明，ＤＭ大鼠系膜区扩张，足突融合，基底膜增厚等，但ＤＰ改变较轻。提示ＤＭ大鼠存在肾脏结构和功能异常；培哚普利对肾脏有保护作用。     

长期抑制大鼠体内内皮衍生舒张因子的生成对其血压及肾功能的影响

本文观察了内皮细胞衍生舒张因子（ＥＤＲＦ）的抑制剂ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅｍｅｔｈｙｌｅｓｔｅｒ（Ｌ－ＮＡＭＥ）在抑制大鼠体内ＥＤＲＦ产生后，对其血压和肾功能的影响。结果表明，Ｌ－ＮＡＭＥ治疗４周后，实验组大鼠的平均动脉压显著升高（Ｐ＜０．０１），其肾小球滤过率和肾血流量明显低于正常对照组，肾血管阻力则高于正常对照组；同时，实验组大鼠２４ｈ尿蛋白定量和尿ＮＡＧ酶排出量均明显高于正常组大鼠，但是，本文的研究结果并不提示实验组大鼠的血浆肾素活性高于正常对照组大鼠。     

环氧化酶及5-脂氧化酶对肾炎模型中肾小球iNOS表达的影响

目的;研究花生四烯酸（ＡＡ）环氧化酶产物及５－脂氧化酶产物对大鼠加速性肾毒性血清性肾炎（ＮＳＮ）中肾小球诱生型一氧化氮合成酶表达的影响。方法：制备ＮＳＮ大鼠模型后,应用消炎痛抑制ＡＡ环氧化酶,应用ＭＫ－０９５１抑制ＡＡ的５－脂氧化酶,观察对肾小球ｉＮＯＳ表达的影响。结果;在ＮＳＮ大鼠,应用消炎痛抑制环氧化酶,可减少肾小球合成的前列腺素（ＰＧ）Ｆ２及血栓素（ＴＸ）Ｂ２,使肾小球ｉＮＯＳ表达增强,尿亚     

早期糖尿病大鼠肾脏诱生型一氧化氮合酶基因表达

目的观察４周糖尿病大鼠肾脏血流动力学变化和肾脏皮、髓质诱生型一氧化氮合酶（ｉＮＯＳ）基因表达情况。方法应用整体廓清试验和半定量逆转录聚合酶链反应（ＲＴＰＣＲ）。结果糖尿病大鼠肾血浆流量（ＲＰＦ４．５４±０．２４ｍｌ／ｍｉｎ／１００ｇｗｔ）、肾小球滤过率（ＧＦＲ１．１５±０．０４ｍｌ／ｍｉｎ／１００ｇｗｔ）显著高于正常（ＲＰＦ３．４４±０．５０，ＧＦＲ０．９４±０．０３）；肾脏皮、髓质ｉＮＯＳｍＲＮＡ水平（经ＧＡＰＤＨ校正）亦明显升高（皮质１．４９±０．０１比正常１．００±０．００８；髓质３．９０±０．０８比正常１．００±０．０９）。结论一氧化氮（ＮＯ）增加可能是糖尿病早期肾脏高灌注、高滤过的重要原因。高水平ＮＯ即可直接扩张肾血管，导致ＲＰＦ、ＧＦＲ升高；又可能通过升高肾间质压，抑制管球反馈参与肾小球高灌注、高滤过的形成     

藻酸双酯钠对阿霉素肾病大鼠保护作用的实验研究

目的：探讨藻酸双酯钠（ＰＳＳ）对肾病综合征（ＮＳ）的疗效及机理，方法：用阿霉素（ＡＤＲ）静脉注射建立大鼠肾病模型，观察大鼠尿蛋白排泄量，测定有关生化指标和凝血功能，并以ｐｏｌｙｅｔｈｙｌｅｎｅｍｉｎｅ（ＰＥＩ）为探针检查肾病大鼠ＧＢＭ阴离子位点，结合组织学及形态学改变，进行远期疗效评估，结果：ＰＳＳ可显著降低肾病大鼠尿蛋白的排泄，纠正脂质代谢紊乱，延缓ＭＣＮＳ发展至ＦＳＧＳ的进程，且对肾小球电荷屏     

去糖基化突变体肾素元的分子特点

应用野生体和去糖基化突变体肾素元ｃＤＮＡ，转染ＧＨ４细胞，经＾３５Ｓ代谢标记表达产物，免疫沉淀，ＳＤＳ．ＰＡＧＥ电泳检测观察去糖基后肾素元结构与功能的变化。发现去糖基化后的肾素元突变体，除半衰期缩短外，其分子粘度明显进高，染细胞清除作为代谢标记去糖基化肾素元的时间延长。     

一氧化氮对实验性肾炎中肾小球花生四烯酸产物的影响

目的：探讨一氧化氮（ＮＯ）在实验性肾小球肾为中对肾小球花生四烯酸（ＡＡ）产物合成的调节作用。方法：制备大鼠加速性肾毒性肾炎（ＮＳＮ）模型,应用市郊和液相层析及放免法测定肾小球合成的前列腺素（ＰＧ）Ｅ２、６－酮－ＰＧＦ１α、血栓素（ＴＸ）Ｂ２、白三烯（ＬＴ）Ｂ４、ＬＴＣ４、５－羟二十碳四烯酸（５－ＨＥＴＥ）、１２－ＨＥＴＥ、１５－ＨＥＴＥ。对ＮＳＮ大鼠应用诱生型ＮＯ合成酶（ｉＮＯＳ）抑制剂Ｌ－ＮＩＬ     

槲皮素对糖尿病大鼠肾脏非酶糖化及氧化的抑制作用

目的探讨槲皮素治疗糖尿病肾病机制。方法对链脲佐菌素诱发糖尿病肾病大鼠给予槲皮素１００ｍｇ·ｋｇ－１·ｄ－１治疗９周，测定糖尿病大鼠体重、肾重、血糖、胰岛素、果糖胺、脂质过氧化物（ＬＰＯ）及超氧化物歧化酶（ＳＯＤ）改变，同时测定肾脏皮质组织ＬＰＯ、果糖胺及晚期糖化终产物（ＡＧＥｓ）、糖化产物（ｐｅｎｔｏｓｉｄｉｎｅ）及脂质过氧化物加合物荧光，并观察尿白蛋白排泄量及肾脏组织病理改变。结果槲皮素对早期糖化产物果糖胺无抑制作用，但对肾脏组织上ＬＰＯ及ＡＧＥｓ、ｐｅｎｔｏｓｉｄｉｎｅ及脂质过氧化物加合荧光均有明显抑制作用，尿白蛋白排泄量明显减少，肾小球基底膜和基质增生均有改善。结论槲皮素通过抑制糖尿病大鼠肾脏组织非酶糖化及氧化，从而对糖尿病肾病有控制作用     

Effect of a low protein diet on the relationship of nonenzymatic glycation to altered renal structure and function in diabetes mellitus

Renal functional parameters including creatinine clearance, urinary albumin excretion, basement membrane thickening, and levels of nonenzymatic glycation of glomerular basement membrane were studied in streptozotocin-induced diabetic rats and age-matched controls subjected to low protein diet. In addition, these parameters were also assessed in diabetic and streptozotocin injected nondiabetic animals fed a 24% protein diet, which served as “positive controls.” While diabetic animals from both diet groups had similar elevated glycated hemoglobin levels and increased levels of nonenzymatic glycation of glomerular basement membrane, these were significantly elevated as compared to insulin treated diabetic (euglycemic), age-matched controls on an 8% protein diet, and streptozotocin injected nondiabetic animals from both diet groups. However, urinary albumin excretion and creatinine clearance levels were significantly elevated only in the 24% protein diet fed diabetics over values seen in the various groups of animals on 8% and controls on 24% protein diet. In contrast, there were no statistical differences among diabetic, euglycemic and control (8% and 24% protein) animals with respect to creatinine clearance, urinary albumin excretion, and glomerular basement membrane thickness. Taken together these data cast some doubt on the role of nonenzymatic glycation in the development of diabetic nephropathy. Moreover, hyperglycemia per se causes a compensatory increase in kidney size irrespective of protein intake; a low protein diet, however, inhibits the hyperfiltration commonly seen in early diabetic nephropathy. The authors, thus, hypothesize that a low protein diet, by preventing compensatory increase in blood flow to surviving nephrons, in some fashion protects these functional units from subsequent damage and possibly delays the onset of renal failure.     

Effect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats

Summary Treatment of diabetic rats with octreotide can inhibit early diabetic renal hypertrophy. Octreotide administration for 6 months from the day of diabetes induction inhibits renal hypertrophy and diminishes increase in urinary albumin excretion. To investigate the effect of octreotide on manifest diabetic renal changes, octreotide treatment was given for 3 weeks after an untreated diabetic period of 3 or 6 months. In addition, following 6 months of diabetes, a group of diabetic rats was treated with insulin for 3 weeks. Renal and glomerular hypertrophy, and increased urinary albumin excretion were observed in diabetic rats compared to non-diabetic control rats from 3 months and throughout the study period. Octreotide treatment did not affect body weight, food intake, blood glucose or serum fructosamine levels. We observed no effect of octreotide treatment on renal and glomerular hypertrophy or urinary albumin excretion compared to placebotreated diabetic rats. Insulin treatment for 3 weeks after 6 months of untreated diabetes normalized blood glucose and serum fructosamine levels, and furthermore renal hypertrophy was significantly diminished compared to the placebo-treated diabetic rats. However, insulin treatment had no effect on glomerular hypertrophy or urinary albumin excretion. In conclusion, octreotide treatment for 3 weeks following an untreated diabetic period of 3 or 6 months is unable to reduce the increased renal and glomerular volume or urinary albumin excretion. However, insulin treatment for 3 weeks with induction of euglycaemia diminishes the renal hypertrophy but has no effect on glomerular volume or urinary albumin excretion.Abbreviations UAE Urinary albumin excretion - IGF-I insulin-like growth factor I - IGFBP insulin-like growth factor binding protein - STZ streptozotocin - TGV total glomerular volume - BW body weight - GH growth hormone - RPF renal plasma flow     

Longitudinal evaluation of the renal clearance of glycated albumin in the diabetic rat

This study has examined glycation of serum albumin and its role in evolving diabetic proteinuria. Renal clearances of endogenous glycated and nonglycated albumin were studied in groups of normal and streptozotocin-induced diabetic Wistar-Kyoto rats over a 32 week period. Concentrations of glycated and nonglycated albumin in serum and urine were measured by rat albumin radioimmunoassay following separation on m-aminophenylboronate affinity columns. Levels of glycated serum albumin in diabetic rats were significantly higher than in normal rats (5.9 +/- 0.7% vs 4.4 +/- 0.3%, P less than 0.05). Median total urinary albumin excretion increased from 120 micrograms/24 h at baseline to 879 micrograms/24 h (P less than 0.05) 28-32 weeks after induction of diabetes. The renal clearance of glycated albumin was approximately twice as great as that of nonglycated albumin in both normal (P less than 0.01) and diabetic (P less than 0.01) rats. However, the glycated albumin/nonglycated albumin clearance ratio in diabetic rats did not correlate with duration of diabetes or with the level of albuminuria. These results indicate that glycation of albumin does not contribute disproportionately to the development of proteinuria in the diabetic rat, during which median renal albumin clearance increased 7-fold. Other factors, such as glycation of the glomerular filtration surface, may have a more important role in the pathogenesis of proteinuria in experimental diabetes.     

Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

An accelerated polyol pathway in diabetes contributes to the development of diabetic complications. To elucidate diabetic nephropathy involving also renal tubular damage, we measured urinary sorbitol concentration concomitantly with urinary N-acetyl-D-glucosaminidase (NAG) excretion in WBN-kob diabetic rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic rats in parallel with whole blood sorbitol concentrations. An increase in 24-h urinary NAG excretion coincided with the elevated urinary sorbitol levels in the diabetic rats. The administration of epalrestat, an aldose reductase inhibitor, reduced the increased whole blood and urinary sorbitol concentrations and urinary NAG excretion concomitantly with renal aldose reductase inhibition in the diabetic rats.These results indicate that diabetic nephropathy involves distorted cell function of renal tubules, and that treatment with epalrestat may prevent at least the progress of the nephropathy.     

橙皮苷对STZ糖尿病大鼠肾脏功能和形态的影响

观察橙皮苷对链脲佐菌素导致的糖尿病大鼠肾脏功能和形态的影响,并与氨基胍进行比较。结果表明:（1）两治疗组大鼠尿蛋白排泄量显著低于对照组P<0.05）;（2）两治疗组肾组织AGEs和LPO含量显著低于对照组（P<0.01,P<0.05）:（3）治疗组肾小球系膜增生和基底膜增厚明显减轻。提示橙皮苷在抑制蛋白非酶糖基化、预防糖尿病肾脏并发症方面具有与氨基胍相似的作用。     

Phosphate depletion with phosphate binder arrests the development of nephropathy in spontaneously hypertensive rats with non-insulin-dependent diabetes mellitus fed a high-protein diet

The protective effect of phosphate binder (PB) on nephropathy was examined in spontaneously hypertensive rats with non-insulin-dependent diabetes mellitus (NIDDM) fed a high-protein diet. The rats were treated with vehicle or streptozocin neonatally. After 14 weeks, all rats were fed a high-protein diet (50% protein content), and in half of the diabetic rats the diets were supplemented with PB. At 24 weeks, the urinary excretion rate of albumin and kidney weight increased in diabetic rats, but decreased or tended to decrease in diabetic rats treated with PB. The elevation of urinary excretion rate of N-acetyl-β-d-glucosaminidase, probably due to protein load, was also abolished with PB.     

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。     

Effects of aminoguanidine and vitamin C on collagen type IV in diabetic nephropathy rats

The aim of this article is to investigate the effects of Aminoguanidine and vitamin C (VitC) on type IV collagen in diabetic nephropathy rats. Diabetic nephropathy rats were induced by intraperitoneal injection of STZ. Rats were randomly divided into five groups: normal control group (n = 10), diabetes group (n = 10), aminoguanidine group (n = 10), VitC group (n = 10), aminoguanidine and VitC group (n = 10). After 16 weeks, the general conditions, blood gloucose, glycosylated hemoglobin, blood urea nitrogen, serum creatinine, serum type IV collagen, urinary albumin excretion rate, and creatinine clearance rate were detected, type IV collagen protein was determined by immunohistochemical analysis as well as the expression of collagen type IVα1 mRNA were determined by in situ hybridization analysis in the kidneys of each group. The results were (1) diabetes mellitus and renal lesions occurred in the diabetes group, aminoguanidine group, VitC group, VitC and aminoguanidine group; (2) aminoguanidine and VitC improved the general conditions of diabetic nephropathy rats, decreased blood urea nitrogen, serum creatinine, and urinary albumin excretion rate as well as increased creatinine clearance rate. The expressions of collagen type IV were significantly down-regulated in treatment groups in contrast to the diabetes group. Aminoguanidine and VitC protect renal lesions in diabetic nephropathy, respectively, by inhibiting expression of type IV collagen, while aminoguanidine and VitC have a synergistic effect on them.     

The relative roles of advanced glycation,oxidation and aldose reductase inhibition in the development of experimental diabetic nephropathy in the Sprague-Dawley rat

Summary Advanced glycation is an important pathogenic mechanism in the development of diabetic complications. However, other biochemical processes, such as the polyol pathway or lipid and protein oxidation which can interact with advanced glycation can also yield tissue fluorescence and may also be implicated in the genesis of diabetic microangiopathy. Aminoguanidine is an inhibitor of advanced glycation, but it is not known if all of its effects are mediated by this mechanism. The present study explores the relative contributions of aldose reductase, oxidative stress and advanced glycation on the development of aortic and renal fluorescence and urinary albumin excretion in streptozotocin diabetic rats. The study groups included non-diabetic (control), streptozotocin diabetic rats and diabetic rats receiving aminoguanidine, the anti-oxidants butylated hydroxytoluene and probucol and the aldose reductase inhibitor, ponalrestat. Serial measurements of glycaemic control and urinary albumin excretion were performed every 8 weeks. At 32 weeks, animals were killed, tissues removed and collagen extracted for measurement of fluorescence. Diabetic rats had increased fluorescence in aorta, glomeruli and renal tubules. Aminoguanidine prevented an increase in fluorescence at all three sites suggesting that diabetes-related tissue fluorescence is predominantly due to advanced glycation. Ponalrestat retarded fluorescence in aorta only and butylated hydroxytoluene attenuated fluorescence at the renal sites but not in the aorta. Diabetic rats had increased renal cortical sorbitol levels. Ponalrestat normalized renal cortical sorbitol levels but aminoguanidine did not affect this parameter. The only agent to decrease plasma thiobarbituric acid reactive substances was butylated hydroxytoluene. Diabetic rats developed albuminuria over the 32-week period. This increase in urinary albumin excretion was only attenuated significantly by aminoguanidine therapy, but not by probucol or ponalrestat. The effects of butylated hydroxytoluene on albuminuria were intermediate between aminoguanidine-treated and untreated diabetic rats. The failure of either antioxidants or aldose reductase inhibition to reproduce the renal effects of aminoguanidine suggest that aminoguanidine may act predominantly via inhibition of advanced glycation and not via the alternative biochemical processes evaluated in this study.Abbreviations AGE Advanced glycated end products - AG aminoguanidine - TBARS Thiobarbituric acid reactive substances - BHT butylated hydroxytoluene