运动对高血压大鼠血压和内皮素的影响

目的：观察原发性高血压大鼠运动后血压、体质量以及血清内皮素的变化。方法：实验于2003-07/09在扬州大学实验动物中心完成。采用18只高血压大鼠作为实验动物，按实验需要将动物分为运动组（10只）和安静组（8只）。运动组经过10周的60min/d的训练，5d/周，与安静组一起测量其血压、体质量；取静脉血，用放射免疫法测定内皮素。结果：实验进行至第5周运动组死亡1只大鼠。①血压：运动前两组大鼠血压无显著差异，经过4，10周运动后运动组大鼠与安静组相比血压明显降低[（174．1&;#177;1.4），（185．0&;#177;1．4）mm Hg；（166．6&;#177;1．1），（193．9&;#177;1．8）mm Hg，P〈0．01]。②体质量：两组动物在生长过程中体质量均逐渐增高，但运动组增长的趋势低于安静组，经10周运动后运动组的体质量明显低于安静组[（344．60&;#177;2．57），（362．00&;#177;5．26）g，P〈0．05]。③内皮素：经过10周的游泳训练后，运动组内皮素明显低于安静组[144．75&;#177;4．45），（68．36&;#177;5．93）ng/L，P〈0.01]。结论：运动对高血压大鼠的体质量增长有抑制作用，且高血压大鼠经过游泳训练后其血内皮素水平下降，而血压也随之下降，提示运动对高血压大鼠的降压部分是通过影响内皮素的产生和释放来实现的。     

50岁以上男性糖尿病肾病血浆内皮素-1和血管紧张素-Ⅱ的水平变化分析

本文探讨了男性在治疗糖尿病肾病(DN)过程中,血浆内ET-1、Ang-Ⅱ含量的变化过程,并与正常人群相比较,并分析了ET-1、Ang-Ⅱ与DN的相互联系,探讨两者与治疗DN的关系.1资料与方法1.1一般资料治疗组:选择DN男性患者75例,年龄51～68(57.78±4.26)岁.患者均出现持续性白蛋白尿(UAER＞200mg/min),且无其他心肺肝脑等疾病.为本院2004-2008年间住院患者.对照组:选择无肾损伤糖尿病男性患者45例,年龄50～70(58.02±5.14)岁.为本院2010-06-2011-04间门诊患者.     

高压氧对糖尿病大鼠血浆内皮素及一氧化氮的影响

目的　研究糖尿病大鼠血浆一氧化氮（ＮＯ） 及内皮素（ＥＴ） 的变化规律,探讨高压氧（ＨＢＯ）治疗糖尿病血管并发症的作用机理。方法　观察糖尿病大鼠ＨＢＯ 作用前,１ ,２ 疗程后血浆ＮＯ及ＥＴ 的变化。结果　与正常对照组相比,糖尿病大鼠对照组早期ＮＯ 升高,ＥＴ 降低,晚期ＮＯ降低,ＥＴ升高,差异均有非常显著性,均Ｐ＜ ０．０１。糖尿病大鼠ＨＢＯ作用组２ 疗程后ＮＯ 为（７ ．４５±０．４５）μｍｏｌ／Ｌ,均较作用前（１０ ．３１ ±０．８３）μｍｏｌ／Ｌ及１ 疗程后（９．９３ ±０．８２）μｍｏｌ／Ｌ 明显降低,均Ｐ＜０．０１,ＥＴ（８９．５８±１８．８８）ｎｇ／Ｌ 较作用前（５０ ．６９ ±１２ ．９４）ｎｇ／Ｌ及１ 疗程后（５３ ．１４±１６．１１）ｎｇ／Ｌ均明显升高,均Ｐ＜ ０．０１。结论　糖尿病大鼠旱期出现高ＮＯ低ＥＴ,晚期出现低ＮＯ高ＥＴ,致糖尿病血管并发症发生,ＨＢＯ 通过延缓晚期低ＮＯ 高ＥＴ 病程,平衡血浆ＮＯ及ＥＴ 的含量而达到治疗糖尿病血管并发症的目的,且多疗程治疗效果更佳     

降钙素基因相关肽、内皮素与2型糖尿病肾病的相关性研究

目的探讨血浆降钙素基因相关肽（CGRP）和内皮素（ET）在2型糖尿病肾病患者的变化趋势,初步探讨CGRP、ET与糖尿病发病机制之间的关系。方法25例健康对照组和83例2型糖尿病患者纳入本研究。根据尿清蛋白排泄率（UAER）将糖尿病患者分为正常清蛋白尿组（28例）、微量清蛋白尿组（29例）和临床清蛋白尿组（26例）。采用放射免疫法分析进行血浆CGRP和ET含量检测。结果2型糖尿病及糖尿病肾病患者血浆ET值较健康对照组显著升高（P〈0．01）,且与UAER呈正相关（r=0．65,P〈0．01）;糖尿病肾病患者CGRP较对照组明显下降（P〈0．05或P〈0．01）,且与UAER呈负相关（r=-0．71,P〈0．01）,ET与CGRP呈显著负相关（r=-0．62,P〈0．01）。结论CGRP与ET水平的失衡参与了糖尿病肾病的发生、发展,导致了肾功能恶化。在糖尿病早期,维持CGRP和ET的动态平衡有利于防治糖尿病肾病的发生、发展。     

运动对高血压大鼠血压和内皮素的影响

目的押观察原发性高血压大鼠运动后血压、体质量以及血清内皮素的变化。方法押实验于2003-07/09在扬州大学实验动物中心完成。采用18只高血压大鼠作为实验动物,按实验需要将动物分为运动组穴10只雪和安静组穴8只雪。运动组经过10周的60min/d的训练熏5d/周,与安静组一起测量其血压、体质量;取静脉血,用放射免疫法测定内皮素。结果押实验进行至第5周运动组死亡1只大鼠。①血压:运动前两组大鼠血压无显著差异熏经过4,10周运动后运动组大鼠与安静组相比血压明显降低眼(174.1±1.4),(185.0±1.4)mmHg;(166.6±1.1),(193.9±1.8)mmHg,P<0.01演。②体质量:两组动物在生长过程中体质量均逐渐增高,但运动组增长的趋势低于安静组,经10周运动后运动组的体质量明显低于安静组眼(344.60±2.57),(362.00±5.26)g,P<0.05演。③内皮素:经过10周的游泳训练后,运动组内皮素明显低于安静组眼穴44.75±4.45雪,穴68.36±5.93雪ng/L,P<0.01演。结论押运动对高血压大鼠的体质量增长有抑制作用,且高血压大鼠经过游泳训练后其血内皮素水平下降,而血压也随之下降,提示运动对高血压大鼠的降压部分是通过影响内皮素的产生和释放来实现的。     

降钙素基因相关肽、内皮素与2型糖尿病肾病的相关性研究

Objective To investigate the tendency of plasma levels of calcitonin gene-related peptide(CGRP)and endothelin(ET)in type 2 diabetic nephropathy,and explore the relationship between calcitonin gene-related peptide,endothelin and pathogenesis of diabetic nephropathy.Methods A total of 25 healthy controls(healthy control group)and 83 patients with type 2 diabetic mellitus(T2DM group)were enrolled in the investigation.According to level s of urinary albumin excretion rate(UAER),the 83 T2DM patients group were further divided into three subgroups:normal UAER subgroup(n=28),microalbuminuira subgroup(n=29)and clinical proteinuria subgroup(n=26).Plasma contents of calcitonin gene-related peptide and endothelin were measured with radioimmunoassay(RIA).Results The level of ET was significantly higher in T2DM group than that in healthy control group(P＜0.01),positively correlative tO UAER(r=0.65,P＜0.01).The plasma level of CGRP was significantly lower in the patients with diabetic nephropathy than the healthy controls,negatively correlative tO UAER(r=-0.71,P＜0.01).There was negative correlation between plasma levels of ET and CGRP(r=-0.62,P＜0.01).Conclusion The disequilibrium of CGRP and ET in plasma might play an important role in the process of diabetic nephropathy.Therefore,keeping balance of levels of CGRP and ET in plasma contributes to prevention and cure of diabetic nephropathy.     

降钙素基因相关肽、内皮素与2型糖尿病肾病的相关性研究

Objective To investigate the tendency of plasma levels of calcitonin gene-related peptide(CGRP)and endothelin(ET)in type 2 diabetic nephropathy,and explore the relationship between calcitonin gene-related peptide,endothelin and pathogenesis of diabetic nephropathy.Methods A total of 25 healthy controls(healthy control group)and 83 patients with type 2 diabetic mellitus(T2DM group)were enrolled in the investigation.According to level s of urinary albumin excretion rate(UAER),the 83 T2DM patients group were further divided into three subgroups:normal UAER subgroup(n=28),microalbuminuira subgroup(n=29)and clinical proteinuria subgroup(n=26).Plasma contents of calcitonin gene-related peptide and endothelin were measured with radioimmunoassay(RIA).Results The level of ET was significantly higher in T2DM group than that in healthy control group(P＜0.01),positively correlative tO UAER(r=0.65,P＜0.01).The plasma level of CGRP was significantly lower in the patients with diabetic nephropathy than the healthy controls,negatively correlative tO UAER(r=-0.71,P＜0.01).There was negative correlation between plasma levels of ET and CGRP(r=-0.62,P＜0.01).Conclusion The disequilibrium of CGRP and ET in plasma might play an important role in the process of diabetic nephropathy.Therefore,keeping balance of levels of CGRP and ET in plasma contributes to prevention and cure of diabetic nephropathy.     

降钙素基因相关肽、内皮素与2型糖尿病肾病的相关性研究

Objective To investigate the tendency of plasma levels of calcitonin gene-related peptide(CGRP)and endothelin(ET)in type 2 diabetic nephropathy,and explore the relationship between calcitonin gene-related peptide,endothelin and pathogenesis of diabetic nephropathy.Methods A total of 25 healthy controls(healthy control group)and 83 patients with type 2 diabetic mellitus(T2DM group)were enrolled in the investigation.According to level s of urinary albumin excretion rate(UAER),the 83 T2DM patients group were further divided into three subgroups:normal UAER subgroup(n=28),microalbuminuira subgroup(n=29)and clinical proteinuria subgroup(n=26).Plasma contents of calcitonin gene-related peptide and endothelin were measured with radioimmunoassay(RIA).Results The level of ET was significantly higher in T2DM group than that in healthy control group(P＜0.01),positively correlative tO UAER(r=0.65,P＜0.01).The plasma level of CGRP was significantly lower in the patients with diabetic nephropathy than the healthy controls,negatively correlative tO UAER(r=-0.71,P＜0.01).There was negative correlation between plasma levels of ET and CGRP(r=-0.62,P＜0.01).Conclusion The disequilibrium of CGRP and ET in plasma might play an important role in the process of diabetic nephropathy.Therefore,keeping balance of levels of CGRP and ET in plasma contributes to prevention and cure of diabetic nephropathy.     

降钙素基因相关肽、内皮素与2型糖尿病肾病的相关性研究

Objective To investigate the tendency of plasma levels of calcitonin gene-related peptide(CGRP)and endothelin(ET)in type 2 diabetic nephropathy,and explore the relationship between calcitonin gene-related peptide,endothelin and pathogenesis of diabetic nephropathy.Methods A total of 25 healthy controls(healthy control group)and 83 patients with type 2 diabetic mellitus(T2DM group)were enrolled in the investigation.According to level s of urinary albumin excretion rate(UAER),the 83 T2DM patients group were further divided into three subgroups:normal UAER subgroup(n=28),microalbuminuira subgroup(n=29)and clinical proteinuria subgroup(n=26).Plasma contents of calcitonin gene-related peptide and endothelin were measured with radioimmunoassay(RIA).Results The level of ET was significantly higher in T2DM group than that in healthy control group(P＜0.01),positively correlative tO UAER(r=0.65,P＜0.01).The plasma level of CGRP was significantly lower in the patients with diabetic nephropathy than the healthy controls,negatively correlative tO UAER(r=-0.71,P＜0.01).There was negative correlation between plasma levels of ET and CGRP(r=-0.62,P＜0.01).Conclusion The disequilibrium of CGRP and ET in plasma might play an important role in the process of diabetic nephropathy.Therefore,keeping balance of levels of CGRP and ET in plasma contributes to prevention and cure of diabetic nephropathy.     

降钙素基因相关肽、内皮素与2型糖尿病肾病的相关性研究

Objective To investigate the tendency of plasma levels of calcitonin gene-related peptide(CGRP)and endothelin(ET)in type 2 diabetic nephropathy,and explore the relationship between calcitonin gene-related peptide,endothelin and pathogenesis of diabetic nephropathy.Methods A total of 25 healthy controls(healthy control group)and 83 patients with type 2 diabetic mellitus(T2DM group)were enrolled in the investigation.According to level s of urinary albumin excretion rate(UAER),the 83 T2DM patients group were further divided into three subgroups:normal UAER subgroup(n=28),microalbuminuira subgroup(n=29)and clinical proteinuria subgroup(n=26).Plasma contents of calcitonin gene-related peptide and endothelin were measured with radioimmunoassay(RIA).Results The level of ET was significantly higher in T2DM group than that in healthy control group(P＜0.01),positively correlative tO UAER(r=0.65,P＜0.01).The plasma level of CGRP was significantly lower in the patients with diabetic nephropathy than the healthy controls,negatively correlative tO UAER(r=-0.71,P＜0.01).There was negative correlation between plasma levels of ET and CGRP(r=-0.62,P＜0.01).Conclusion The disequilibrium of CGRP and ET in plasma might play an important role in the process of diabetic nephropathy.Therefore,keeping balance of levels of CGRP and ET in plasma contributes to prevention and cure of diabetic nephropathy.     

Effects of low-protein diet on experimental diabetic nephropathy in the rat

To evaluate the role of glomerular hyperfiltration in the development and progression of diabetic nephropathy, we performed clearance and histopathologic studies in 24 rats with streptozocin-induced diabetes after 3 months of diets with different protein compositions. Calcium phosphate was added to an 8% protein diet in group I (nine rats), and calcium carbonate to a 24% protein diet in group II (nine rats) to equalize calcium and phosphate contents in these diets. Group I and II rats also received small doses of insulin to reduce the excessive hyperglycemia induced by the high sucrose content of the diets. In group III, six rats given an 8% protein diet, no calcium, phosphate, or insulin was added. In groups I and III, low dietary protein significantly reduced glomerular filtration rate and renal plasma flow per gram of kidney weight as compared with rates observed in group II rats with a higher protein intake. Features of diabetic glomerulopathy including mesangial hypercellularity and mesangial matrix expansion were also significantly milder in the groups with a low protein diet. On the other hand, medullary calcification and interstitial changes were most prominent in group I, given calcium phosphate supplement; the increase in the kidney weight was greater in groups I and II, which received insulin, than in group III, which did not. It was concluded that low protein diet significantly ameliorates diabetic glomerulopathy but that supplementation with inorganic phosphate in an amount equal to organic phosphate contained in the higher protein diet causes medullary calcification and interstitial nephritis. Also, administration of suboptimal doses of insulin in diabetic animals greatly enhances renal growth, more than that induced by diabetes alone.     

Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats

The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5 mg/kg) alone or in combination with rosuvastatin (RSU) (10 mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats.     

Soybeans ameliolate diabetic nephropathy in rats

Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented.     

尿Ⅳ型胶原在实验性糖尿病肾病大鼠中的变化及意义

目的观察实验性糖尿病大鼠尿Ⅳ型胶原的变化并探讨其与糖尿病肾病其他检测指标的关系.方法实验于2002-02/2004-10在大连医科大学中心实验室完成.①分组取雄性SD大鼠54只,随机分成对照组24只和模型组30只.②动物模型建立尾静脉一次性注射链尿佐菌素(55 mg/kg),测血糖≥16.7 mmol/L,尿糖持续阳性大鼠定为糖尿病模型动物.符合标准的为糖尿病组24只,对照组注射等量柠檬酸钠缓冲液.③检测方法及观测指标两组分别于病程的第2,3,6,9周随机取6只大鼠,经测定尿白蛋白正常而尿Ⅳ型胶原增高的糖尿病大鼠为糖尿病肾病待定组(n=5).随后麻醉状态下处死大鼠,检测血糖、血肌酐、肌酐清除率;用病理图像自动分析仪测定肾小球平均体积、PAS阳性物质含量.结果对照组大鼠24只,糖尿病模型组大鼠24只,糖尿病肾病待定组大鼠5只全部进入结果分析.①糖尿病组2,3,6,9周,尿Ⅳ型胶原、尿白蛋白、肌酐清除率均显著高于对照组(P＜0.05～0.001);病程第2周,尿Ⅳ型胶原增高109.1%,尿白蛋白仅增高23.7%.②糖尿病肾病待定组肾小球平均体积、肌酐清除率均高于正常参考值[肾小球平均体积(1×103 mm3)糖尿病肾病待定组分别为498.88,498.88,470.05,468.26,490.44,正常参考值为(244.1～322.1)×103 mm3;肌酐清除率(mL/min·kg)分别为7.36,9.52,11.62,7.57,9.69,正常参考值为(1.73～4.33)mL/min·kg].③尿Ⅳ型胶原与血肌酐、尿白蛋白正相关(r=0.63,0.88,P＜0.001),与PAS灰度、肌酐清除率负相关(r=-0.71,-0.45,P＜0.001).结论尿Ⅳ型胶原能更早、更敏感地对糖尿病肾病作诊断,并且还能监测病情的发展变化.     

洛伐他汀对糖尿病大鼠肾功能及肾脏组织p38丝裂原激活蛋白激酶表达的影响

目的 探讨洛伐他汀对糖尿病(DM)大鼠肾小球结构、功能及肾组织p38丝裂原活化蛋白激酶(MAPK)及其下游转录因子cAMP反应元件结合蛋白(cREB)表达的影响。方法 18只雄性Wistar大鼠行右肾切除术2周后,随机分为3组:右肾切除对照组、DM组和洛伐他汀治疗组每组6只。DM组和洛伐他汀组腹腔注射链脲佐菌素(STZ,65 mg／kg)诱发DM模型,洛伐他汀组制模后1 d每日给予洛伐他汀20 mg／kg灌胃。分别于注射STZ后4周收集大鼠尿液,测定尿蛋白(Upro)、尿肌酐(UCr);股动脉放血分离血清,测定血糖(Glu)、血肌酐(SCr)、尿素氮(BUN)、胆固醇(CHO)和甘油三酯(TG),并计算肌酐清除率(CCr)。免疫组化检测肾皮质磷酸化p38 MAPK(P-p38 MAPK)及磷酸化CREB(P-CREB)的表达特征,并检测转化生长因子-β1(TGF-β1)、纤维粘连蛋白(FN)及层粘连蛋白(LN)的表达,应用图像分析系统进行定量分析。流式细胞术检测P-p38 MAPK和P-CREB蛋白的表达,Western印迹法检测肾皮质P-p38 MAPK和P-CREB活性的变化。结果 与对照组相比,4周时DM组P-p38 MAPK、P-CREB、TGF-β1、FN及LN表达均明显升高(P均<0.01);而与DM组相比,洛伐他汀组各指标的表达有不同程度的降低(P均<0.01)。结论 洛伐他汀对DM大鼠肾脏结构和功能具有保护作用,可能通过调节p38 MAPK和CREB蛋白的表达     

A study on the effects to diabetic nephropathy of Hachimi-jio-gan in rats

To investigate the effects of Hachimi-jio-gan on diabetic nephropathy, we employed an animal model, rats subjected to sub-total nephrectomy followed by streptozotocin injection, and administered Hachimi-jio-gan orally at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. The administration of Hachimi-jio-gan reduced dose-dependently the elevated blood glucose and urinary protein excretion levels in rats with diabetic nephropathy over the experimental period, whereas it increased creatinine clearance significantly, suggesting that Hachimi-jio-gan would prevent or delay the progression of diabetic nephropathy. In addition, the serum glycosylated protein and urea nitrogen levels were markedly elevated in rats with diabetic nephropathy compared with normal rats, and were significantly reduced by the administration of Hachimi-jio-gan, whereas Hachimi-jio-gan reversed the decrease in the serum albumin level. The serum triglyceride and total cholesterol concentrations were reduced by Hachimi-jio-gan, implying that Hachimi-jio-gan would improve the metabolic disorder of lipids caused by diabetic nephropathy. Moreover, Hachimi-jio-gan inhibited lipid peroxidation in the serum and kidney, which suggests that Hachimi-jio-gan would ameliorate oxidative stress associated with diabetic nephropathy. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were also normalized by the administration of Hachimi-jio-gan through decreases in advanced glycation end-product formation and sorbitol levels in the kidney. Hachimi-jio-gan protected against the development of renal lesions, glomerular sclerosis, tubulointerstitial lesions, mesangial matrix expansion and arteriolar sclerosis, estimated by histopathological evaluation and scoring. This study suggests that Hachimi-jio-gan may be a novel therapeutic approach to improving diabetic nephropathy.     

Effect of aspirin on experimental diabetic nephropathy

The decline in glomerular filtration rate (GFR) in long-term diabetes in humans and animals in preceded by a period of hyperfiltration that may be responsible for it. The mediators of the increase in glomerular filtration are unknown, but recent studies suggest a prominent role for prostaglandins. To test the hypothesis that prostaglandins mediate early hyperfiltration and contribute to the progression of diabetic nephropathy, we examined the effects of long-term aspirin (ASA) treatment on whole kidney GFR and renal prostaglandin E2 (PGE2) synthesis in control and diabetic rats 8 days and 16 weeks after streptozocin administration. The rats were divided into four groups, control, control with ASA (C/ASA), diabetic, and diabetic with ASA (D/ASA). We found that 8 days after streptozocin treatment, PGE2 synthesis and GFR were increased in diabetic rats. ASA treatment inhibited renal prostaglandin synthesis and prevented the GFR increase. ASA given to control rats reduced PGE2 synthesis without changing GFR. In the 16-week study diabetic rats had lower GFR and increased renal PGE2 synthesis. Diabetic rats also had thickened glomerular basement membrane compared with control rats. By contrast GFR did not fall and thickening of the glomerular basement membrane did not occur in diabetic rats receiving ASA. ASA had no effect on GFR or glomerular basement membrane in normal rats but decreased renal PGE2 synthesis. The data demonstrate that aspirin prevents early hyperfiltration and prevents the fall in GFR and glomerular basement membrane thickening that occurs over time in diabetic rats. Inhibition of PGE2 synthesis by aspirin, or some other effect of aspirin, may be responsible for the protection observed.     

厄贝沙坦联合金水宝对糖尿病肾病大鼠蛋白尿发生机制影响的研究

目的研究厄贝沙坦联合金水宝对糖尿病肾病(DN)大鼠足细胞裂孔隔膜Podocin的表达影响,探讨DN蛋白尿的发生机制。方法建立糖尿病肾病大鼠动物模型。将动物随机分为厄贝组、金水宝组、联合组、糖尿病肾病组,另设正常对照组。12周后观察尿蛋白,用免疫组化、RT-PCR检测Podocin的表达,并观察Podocin与24尿蛋白的相关性。结果 1联合用药组较单用药组24 h尿蛋白量明显下降(P0.05)。2联合用药组较单用药组Podocin蛋白表达、Podocin mRNA有明显升高(P0.05)。3Podocin蛋白表达量和24 h尿蛋量具有显著负相关性(r=-0.889,P0.001);而Podocin mRNA和24 h尿蛋白量具有显著正相关关系(r=0.933,P0.001)。结论厄贝沙坦联合金水宝较单用药显著减轻糖尿病肾病大鼠早期蛋白尿,通过上调足细胞Podocin的表达,更好地保护肾小球滤过屏障。