济肾汤对糖尿病大鼠肾脏病变改善作用的机制

目的探讨济肾汤对实验性糖尿病大鼠肾脏病变改善作用的机制。方法诱发大鼠糖尿病４周后，济肾汤给药８周，评价济肾汤对糖尿病大鼠肾脏自由基代谢紊乱和非酶促糖基化作用的影响。结果济肾汤处理可明显提高糖尿病大鼠肾脏超氧化物歧化酶（ＳＯＤ）和过氧化氢酶（ＣＡＴ）活性，降低肾脏和尿液脂质过氧化物丙二醛（ＭＤＡ）水平，显著减少肾皮质５羟甲基糠醛（５ＨＭＦ）释放量和肾小球系膜区硝基四氮唑蓝（ＮＢＴ）染色强度。结论减轻肾脏自由基代谢紊乱和抑制非酶促糖基化可能是济肾汤改善糖尿病大鼠肾脏病变的重要机制。     

晚期糖基化终末产物和蛋白激酶C对糖尿病大鼠肾脏的影响

目的探讨糖尿病状态下肾小球晚期糖基化终末产物（ＡＧＥ）与蛋白激酶Ｃ（ＰＫＣ）的关系及其对肾脏的影响。方法给予糖尿病大鼠胰岛素和氨基胍治疗，测定血糖，糖化血红蛋白Ａ１Ｃ（ＨｂＡ１Ｃ）、肾小球ＡＧＥ（ＧＴＥＡＧＥ）、蛋白激酶Ｃ（ＰＫＣ）、肾小球基底膜厚度（ＧＢＭＴ）和尿Ｐｒ／Ｃｒ比值。结果糖尿病大鼠在血糖、ＨｂＡ１Ｃ和ＡＧＥ水平增高的同时，ＰＫＣ活性、尿Ｐｒ／Ｃｒ比值和ＧＢＭＴ都显著增加（Ｐ值小于００１）；胰岛素可减少ＨｂＡ１Ｃ和ＡＧＥ形成，恢复ＰＫＣ活性，氨基胍可减少ＡＧＥ形成，但对ＰＫＣ活性无影响。两种药物均可减缓尿Ｐｒ／Ｃｒ比值和ＧＢＭＴ增加（Ｐ＜００１或Ｐ＜００５）。结论慢性高血糖可增高肾小球ＰＫＣ活性，非酶促糖基化可能未直接参与ＰＫＣ活性改变，但ＰＫＣ可加强ＡＧＥ对肾脏的影响。减少ＡＧＥ形成，改善ＰＫＣ活性对糖尿病肾病的防治尤为重要。     

冬虫夏草对5／6肾切除大鼠肾脏病理改变的影响

冬虫夏草对５／６肾切除大鼠肾脏病理改变的影响程庆，于力方，师锁柱，陈香美ＥＦＦＥＣＴＯＦＣＯＲＤＹＣＥＰＳＳＩＮＥＮＳＩＳＯＮＲＥＮＡＬＨＩＳＴＯＬＯＧＩＣＡＬＣＨＡＮＧＦＳＩＮ５／６ＮＥＰＨＲＥＣＴＯＭＩＺＥＤＲＡＴ￥ＣｈｅｎｇＱｉｎｇｌｉ；ＹｕＬ...     

大鼠阳离子化牛血清白蛋白肾炎肾脏前列腺素来源的探讨

目的 探讨大鼠阳离子化牛血清白蛋白（Ｃ－ＢＳＡ）肾炎中肾脏前列腺素来源。方法 应用羊抗大鼠血小板血清ＩｇＧ，对大鼠Ｃ－ＢＳＡ肾炎模型进行干扰。结果 实验组大鼠肾皮质ＰＧＥ２、ＰＧＩ２、ＴＸＡ２均减少，肾小球病理损害减轻，尿蛋白减少。结论 血小板参与Ｃ－ＢＳＡ肾炎病理过程以及肾脏前列腺素部分来源于血小板。     

晚期非酶糖基化终末产物与糖尿病肾病

非酶糖基化终末产物（ＡＧＥｓ）可以造成组织细胞结构和功能的损害。ＡＧＥｓ可以引起肾脏细胞外基质的堆积，影响细胞代谢，诱发蛋白尿和肾小球肥大，在糖尿病肾病的发生和发展中起着重要作用。     

氨基胍对糖尿病大鼠肾组织中内皮素及其受体基因表达的作用

目的探讨非酶糖化作用对糖尿病大鼠肾组织中内皮素及其受体基因表达的影响。方法采用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）技术，观察糖尿病大鼠肾皮质中内皮素及其受体基因表达的变化，以及氨基胍对其表达的影响。结果诱发糖尿病８周的大鼠肾皮质内ＥＴ－１及ＥＴ－Ａ受体的基因表达明显增加，ＥＴ－３ｍＲＮＡ水平与正常相比未见明显改变，但ＥＴ－Ｂ受体ｍＲＮＡ表达下降。氨基胍给药使糖尿病大鼠肾皮质内增加的ＥＴ－１及ＥＴ－Ａ受体ｍＲ－ＮＡ水平明显降低，同时使ＥＴ－３及ＥＴ－Ｂ受体ｍＲＮＡ表达明显增加。结论糖尿病状态下，ＥＴ－１、ＥＴ－３可能以不同的方式参与肾脏结构和功能的改变；氨基胍治疗能有效地调节糖尿病肾组织内异常的ＥＴ及其受体的基因表达，缓解肾脏损害。     

大鼠原位性肾炎肾皮质内前列腺素含量变化

大鼠原位性肾炎肾皮质内前列腺素含量变化李成进，李士梅，何柏林，姜傥，董秀清ＴＨＥＣＨＡＮＧＥＳＯＦＥＩＣＯＳＡＮＯＩＤＰＲＯＤ－ＵＣＴＩＯＮＩＮＴＨＥＲＡＴＲＥＮＡＬＣＯＲＴＥＸＳＩＮＩＮ－ＳＩＴＵＧＬＯＭＥＲＵＬＯＮＥＰＨＲＩＴＩＳ￥ＬｉＣｈｅｎｇ...     

晚期非酶糖基化终末产物与糖尿病肾病

非酶糖基化终末产物可以造成组织细胞结构和功能的损害。ＡＧＥＳ可以引起肾脏细胞外基质的堆积，影响细胞代谢，诱发蛋白尿和肾小球肥大，在糖尿病肾病的发生和发展中起着重要作用。     

一氧化氮在糖尿病肾病中的作用

目的探讨糖尿病（ＤＭ）和高血压大鼠肾脏一氧化氮（ＮＯ）途径与ＤＭ肾病的关系。方法将自发性高血压大鼠（ＳＨＲ）制成链脲佐菌素（ＳＴＺ）ＤＭ模型。设ＷＫＹ、ＳＨＲ和ＳＨＲＤＭ三组。除形态学观察外,还测定各组大鼠肌酐清除率（Ｃｃｒ）、２４小时尿蛋白、血及肾组织ＮＯ含量、肾脏ＮＯ合成酶（ＮＯＳ）活性和ＮＯＳｍＲＮＡ表达水平。结果ＳＨＲＤＭ组大鼠２４小时尿蛋白定量２０周时明显高于其余两组,Ｃｃｒ无明显改变。血ＮＯ水平升高,肾ＮＯ含量降低。肾脏结构型ＮＯＳ（ｃＮＯＳ）活性下降,诱导型ＮＯＳ（ｉＮＯＳ）活性或ｉＮＯＳ／ｃＮＯＳ（ｉ／ｃ）比值增加。肾小球ＮＯＳｍＲＮＡ表达面积扩大,入球动脉及小叶间动脉ＮＯＳ基因表达明显下降。肾小球系膜增生,有形成ＫＷ结节或纤维蛋白帽的趋势,系膜区基质增多,基底膜增厚,肾小动脉壁厚腔窄。结论（１）ＳＴＺＳＨＲＤＭ模型出现的２４小时尿蛋白增加、肾小球系膜及肾小血管病变提示ＤＭ肾病的产生;（２）肾脏ＮＯ系统异常与ＤＭ肾病有关。     

肾皮质厚度测定对肾脏疾病诊断及预后判断的意义

肾皮质厚度测定对肾脏疾病诊断及预后判断的意义俞雨生，黎磊石，姚小丹，王庆文，章旭，刘传华，杨斌，付宁华，程绍华ＴＨＥＩＭＰＯＲＴＡＮＣＥＯＦＭＥＡＳＵＲＥＭＥＮＴＯＦＴＨＥＣＯＲＴＩＣＡＬＴＨＩＣＫＮＥＳＳＩＮＴＨＥＤＩＡＧＮＯＳＩＳＯＦＲＥＮＡＬＤ...     

The Protective Effects of Taurine against Early Renal Injury in STZ-Induced Diabetic Rats,Correlated with Inhibition of Renal LOX-1-Mediated ICAM-1 Expression

Oxidative stress is a key cause in the development of diabetic nephropathy (DN). As a main receptor of oxidized low-density lipoprotein (oxLDL), LOX-1 plays an important role in the induction of leukocyte adhesion molecules, such as intercellular cell adhesion molecule-1 (ICAM-1). Taurine (TAU), a potent endogenous antioxidant, showed renoprotective effects in several model animals. This study was designed to determine the renoprotective effect and possible mechanism involved LOX-1 and ICAM-1 expression of taurine in early DN. Six-week-old male Wistar rats were divided into three groups: normal control (NC), diabetes mellitus (DM), and taurine-treated DM (DM+TAU). Diabetes was induced by streptozotocin (STZ, 60 mg/kg, i.p.). After the onset of diabetes, drinking water containing 1% taurine was given to rats in the DM+TAU group. After six weeks of treatment, blood glucose (BG), serum levels of creatinine (sCr) and BUN, and LOX-1 and ICAM-1 expression (protein and gene) in kidney cortices were estimated. Meanwhile, renal malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were examined as parameters of oxidative stress in diabetic rats. For DM+TAU rats, when compared with DM rats, the levels of serum BUN, sCr, and renal MDA were reduced, and the activities of renal GSH-Px were increased, but the BG levels were not influenced. Simultaneously, taurine attenuated histopathologic evidence of renal damages and reduced the overexpression of LOX-1 and ICAM-1 in kidney cortices of diabetic rats. In conclusion, taurine showed protective effects against early renal injury in diabetic rats. These renoprotective effects may be partly caused by suppression of oxLDL/LOX-1 system and subsequently ICAM-1 overexpression on renal cortex via its antioxidative property.     

Glomerular nonenzymatic glycosylation and lipid peroxide are increased in the early phase of streptozotocin-induced diabetic rats prior to major histopathologic alterations.

Levels of glomerular nonenzymatic glycosylation and lipid peroxide in streptozotocin (STZ)-induced diabetic rats were examined. Isolation of glomeruli was performed using a sieving technique. The levels of nonenzymatic glycosylation in the glomeruli of these rats were measured by the thiobarbituric acid (TBA) method. Measurement of lipid peroxide, i.e., malondialdehyde (MDA), levels in the renal cortex, medulla and isolated glomeruli was performed by the TBA test. Light-microscopic and immunofluorescent examinations were also performed. An increase in nonenzymatic glycosylation in the glomeruli was observed in the early phase, i.e., after 4 and 12 weeks, in STZ-induced diabetic rats. The levels of MDA in the renal cortex of 12-week-old STZ-induced diabetic rats were also significantly increased compared with those of control rats at the same age. Levels of MDA in the glomeruli of 12-week-old STZ-induced diabetic rats were slightly increased compared with those of control rats, but there was no statistical significance. In immunofluorescence, IgG or IgM was deposited in the glomerular mesangial areas and capillary walls in 12-week-old diabetic rats. However, there was no significant change in renal tissues after 4 and 12 weeks in STZ-induced diabetic rats. It was concluded that glomerular nonenzymatic glycosylation and lipid peroxide were already increased in the early phase of STZ-induced diabetic rats prior to the appearance of marked histologic alterations.     

Taurine protected kidney from oxidative injury through mitochondrial-linked pathway in a rat model of nephrolithiasis

Hyperoxaluria and crystal deposition induce oxidative stress (OS) and renal epithelial cells injury, both mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are considered as the main sources of reactive oxygen species (ROS). Taurine is known to have antioxidant activity and shows renoprotective effect. We investigate the effect of taurine treatment on renal protection, and the putative source of ROS, in a rat model of calcium oxalate nephrolithiasis. Rats were administered with 2.5% (V/V) ethylene glycol + 2.5% (W/V) ammonium chloride (4 ml/day), with restriction on intake of drinking water (20 ml/day) for 4 weeks. Simultaneous treatment with taurine (2% W/W, mixed with the chow) was performed. At the end of the study, indexes of OS and renal injury were assessed. Renal tubular ultrastructure changes were analyzed under transmission electron microscopy. Crystal deposition in kidney was scored under light microscopy. Angiotensin II in kidney homogenates was determined by radioimmunoassay. Expression of NADPH oxidase subunits p47phox and Nox-4 mRNAs in kidney was evaluated by real time-polymerase chain reaction. The data showed that oxidative injury of the kidney occurred in nephrolithiasis-induced rats. Hyperplasia of mitochondria developed in renal tubular epithelium. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria decreased and the mitochondrial membrane showed oxidative injury. Taurine treatment alleviated the oxidative injury of the kidney, improved SOD and GSH-Px activities, as well as the mitochondrial membrane injury, with lesser crystal depositions in the kidney. We could not detect statistical changes in the renal angiotensin II level, and the renal p47phox and Nox-4 mRNAs expression in those rats. The results suggest that mitochondria but not NADPH oxidase may account for the OS and taurine protected kidney from oxidative injury through mitochondrial-linked pathway in this rat model.     

Effects of angiotensin II on the renal antioxidant activities of borderline hypertensive rats

This study was aimed to study the angiotensin II (Ang II)-induced antioxidant changes in the kidney of borderline-hypertensive rats (BHR). We measured renal antioxidant enzyme activities, and glutathione (GSH) contents and lipid peroxide levels in relation to the age of subjects. In the antioxidant enzyme assays, consistent changes were not observed in relation to age. However, in the assay for reduced GSH, nonenzymatic antioxidant, contents of adult and aged rats were much greater than those of weanling rats. Subcutaneous injection of pressor dose of human Ang II (200 microg/kg over 90 min) significantly reduced enzymatic activities in the weanling (4-week-aged) and adult (10-week-aged) BHR. However, in the relatively aged (16-week-aged) rats, Ang II did not alter enzymatic activities. Renal GSH contents of aged BHR, were highly increased by Ang II. Renal lipid peroxide levels of weanling and adult BHR were increased by Ang II, but decreased in the aged rats. However, these characteristic changes of renal antioxidant due to Ang II of the BHR could not be observed in the age-matched control, Wistar-Kyoto rats (WKR). From these results, it can be concluded that impacts of oxidative stress on the kidney of BHR may be greater in the young rats.     

Effect of irbesartan on the antioxidant defence system and nitric oxide release in diabetic rat kidney

BACKGROUND/AIMS: Increased oxidative stress is involved in the aetiology of diabetic nephropathy, and angiotensin II is reported to play a considerable role in the development of renal damage in diabetic kidney. Angiotensin antagonism can slow the progression of renal impairment in diabetes. The present study was thus designed to examine the effect of an angiotensin II type 1 (AT1) receptor antagonist, irbesartan on renal function, oxidative stress and nitric oxide (NO) release in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with irbesartan (25 and 50 mg/kg, orally) respectively till 8 weeks starting from 4 weeks after STZ injection. Renal function was assessed by creatinine, blood urea nitrogen, creatinine clearance and urea clearance. Oxidative stress was measured by renal malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase. We also measured renal nitrite levels. RESULTS: At the end of the 8th week, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, GSH, SOD and catalase in diabetic rats. NO release was also significantly higher in diabetic rats than controls. Chronic treatment with irbesartan in diabetic rats significantly attenuated both renal dysfunction and oxidative stress along with increased NO levels as compared with untreated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas irbesartan administration markedly prevented diabetic-induced renal morphological alterations. CONCLUSIONS: The present study suggests that oxidative stress/nitrosative stress is increased in the diabetic kidney and AT1 receptor blockade can prevent these changes. The results also suggest that in STZ-induced diabetic rats, the protective action of irbesartan might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.     

Oxidative stress occurs in absence of hyperglycaemia and inflammation in the onset of kidney lesions in normotensive obese rats.

BACKGROUND: Several factors favour the development of kidney lesions. We examined the role of oxidative stress in the onset of renal alterations that occur in Zucker obese (ZO) fa/fa rats. METHODS: Kidney structure, biological data, glycation parameters, advanced glycation end products (AGE), thiobarbituric acid-reactive substances (TBARS), circulating antibodies anti-malondialdehyde (MDA)-modified low-density lipoprotein (LDL), antioxidant defenses (Cu/Zn and Mn superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) activities, glutathione level), were determined in plasma and/or kidney of young and old ZO rats and lean (ZL) Fa/fa littermates. RESULTS: Renal lesions and functional decline appeared at 3 months in hyperlipidaemic, hyperinsulinaemic, normotensive ZO rats, independently of any macrophage-ED(1)(+)-cell infiltration. At 6 months and thereafter, kidney lesions and functional impairment worsened while numerous ED(1)(+)-cells invaded the interstitium. At 3 and 9 months, TBARS level in the LDL/very low-density lipoprotein fraction and in the kidney was higher in ZO than in ZL rats. Anti-MDA-LDL antibodies were increased in ZO rats. At 3 months, renal activity of Cu/Zn SOD was higher, and activities of catalase and GPx lower in ZO than in ZL rats, leading to an accumulation of hydrogen peroxide (H(2)O(2)). At 9 months, a decrease in Cu/Zn SOD activity and an increase in glutathione level were observed. Blood glucose and glycated proteins, as well as AGE in kidney, remained similar in both ZL and ZO rats, whatever their age. CONCLUSION: These data suggest that oxidative stress triggers, at an early age, the onset of kidney lesions and functional impairment in ZO rats, in absence of hyperglycaemia, hypertension and inflammation.     

Pancreas transplantation prevents cellular oxidative stress in kidneys of alloxan-induced diabetic rats

PURPOSE: Oxidative stress is one of the most important mechanisms to explain genesis of the complications in the chronic progression of diabetes. In this investigation we studied the effects of pancreas transplantation (PT) on the imbalance caused by excessive production of free oxygen radicals by antioxidant defenses of rats with serious chronic hyperglycemia induced by alloxan. METHODS: Ninety inbred male Lewis rats were randomly distributed into three groups: NC-30 nondiabetic controls; DC-30 diabetic controls without any treatment; PT-30 diabetic rats undergoing syngeneic PT from normal donor Lewis rats. Each experimental group was then split into three subgroups of 10 animals for sacrifice after 1, 3, or 6 months. Clinical and laboratory parameters from all rats as well as lipid hydroperoxide (LPO) concentrations and renal tissue enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were recorded for all rats. RESULTS: Successful PT corrected clinical and laboratory alterations in diabetic rats with sustained normoglycemia throughout the study. A significant increase in LPO concentration and a marked reduction in SOD and CAT enzyme activity were observed in DC rats; there was no significant variation in renal tissue GSH-Px in this group. However, alterations in DC rats were completely restored from 1st month after PT; all evaluated enzyme levels did not significantly differ (P < .01) from those in NC controls. CONCLUSION: Successful PT controlled cellular oxidative stress in diabetic kidneys, which may prevent chronic lesions.     

中药芪卫颗粒对2型糖尿病大鼠肾脏氧化应激及病理改变的影响

目的：观察中药芪卫颗粒对2型糖尿病大鼠肾脏氧化应激与病理改变的影响。方法：采用高脂喂养联合低剂量（30mg/kg）链脲佐菌素诱导2型糖尿病大鼠模型。将糖尿病模型大鼠随机分为模型组、芪卫颗粒组、α-硫辛酸组,正常鼠为正常对照组,每组8只。芪卫颗粒组予芪卫颗粒按生药20g.kg-1.d-1灌胃,α-硫辛酸组予α-硫辛酸20mg.kg-1.d-1灌胃,其他两组大鼠予等体积蒸馏水灌胃。连续处理12周,检测血糖、糖化血红蛋白、血脂、尿蛋白排泄量、肾功能等指标的变化以及肾皮质中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性和丙二醛（MDA）含量的变化;观察肾脏病理改变。结果：与正常对照组比较,各组糖尿病大鼠尿蛋白排泄量明显增加（P〈0.01）,肌酐清除率降低（P〈0.05）;肾皮质MDA含量明显升高（P〈0.01）,而SOD、GSH-Px活性则显著降低（P〈0.01）;病理学观察显示肾小球肥大,肾小球毛细血管基底膜不均匀增厚,系膜细胞增生,系膜基质增多,肾小管上皮细胞肥大,肾小管间质胶原纤维明显增加。经芪卫颗粒、α-硫辛酸处理后,上述改变较模型组明显减轻（P〈0.01或0.05）,但两治疗组之间各指标差异无统计学意义（P〉0.05）。结论：氧化应激可能在糖尿病肾病的发生、发展中发挥重要作用。中药芪卫颗粒能有效抑制2型糖尿病大鼠肾脏的氧化应激反应,改善肾脏功能和结构变化。