小儿肾脏疾病血,尿内皮素的变化

目的研究小儿肾脏疾病血、尿内皮素（ＰＥＴ、ＵＥＴ）的水平及其相互关系。方法采用同位素放免方法检测了肾病综合征（ＮＳ），肾小球肾炎（ＧＮ），肾功能衰竭（ＲＦ）共７２例患儿血及尿中ＥＴ，血心钠素（ＡＮＰ）水平。结果ＮＳ，ＧＮ，ＲＦ三组的ＰＥＴ及ＵＥＴ值明显高于对照组，尤其ＲＦ组（Ｐ＜００５，Ｐ＜０．０１）。ＡＮＰ值在ＧＮ组和ＲＦ组明显高于对照组（Ｐ＜００１）。８例ＡＲＦ患儿恢复期血ＥＴ水平下降，６例ＣＲＦ患儿虽经治疗，但血ＥＴ水平不降或上升。结论ＥＴ在小儿肾脏疾病发病机理及病情进展中可能起重要作用，其值高低与病情严重程度及预后有关。     

糖尿病患者肾血流与内皮素及降钙素基因相关肽关系

目的为了解内皮素（ＥＴ）及降钙素基因相关肽（ＣＧＲＰ）与糖尿患者不同阶段时肾血流的关系。方法肾彩色多普勒超声检查确定为糖尿病肾血流正常组（Ａ组）１５例、糖尿病肾血流减少组（Ｂ组）１５例，正常对照组１８例。分别采血测定血浆ＥＴ－１和ＣＧＲＰ浓度。结果Ａ组ＥＴ－１水平低于正常对照组（Ｐ＜０．０１），Ｂ组ＥＴ－１水平高于正常对照组（Ｐ＜０．０１）。二组ＥＴ－１水平与肾动脉收缩期峰值血流速度（Ｖｍａｘ）、肾动脉血流量（Ｑ）呈负相关（Ｐ＜０．０１），与尿白蛋白排泄率（ＵＡＥＲ）呈正相关（Ｐ＜０．０５）。二组的ＣＧＲＰ水平均低于正常组（Ｐ均＜０．０１），但Ａ与Ｂ组的ＣＧＲＰ水平差异无显著性（Ｐ＞０．０５）。未发现ＣＧＲＰ水平与Ｖｍａｘ、Ｑ和ＵＡＥＲ呈相关关系。结论ＥＴ－１在糖尿病不同阶段时对肾血流量的病理生理作用可能不同；糖尿病患者呈现低ＣＧＲＰ血症，但它对不同阶段的糖尿病肾血流的影响尚有待探讨。     

一氧化氮供体防治急性缺血性肾衰的实验研究

为了进一步证实一氧化氮（ＮＯ）在急性缺血性肾衰（ＩＡＲＦ）发生发展中的作用，采用ＮＯ供体ＳＩＮ１对大鼠ＩＡＲＦ模型进行腹主动脉持续灌注３小时。结果发现：ＮＯ供体输入体内可在肾内迅速产生高浓度ＮＯ，可明显改善肾缺血再灌注后的肾皮质缺血，减轻肾功能及组织学损害。结果表明：ＮＯ下降参与了缺血再灌注的肾功能损害，是ＩＡＲＦ发生发展的重要因素之一。ＮＯ缺乏主要导致肾血流量下降，继而ＧＲＦ下降。应用ＮＯ供体直接提供外源性ＮＯ，提高肾内ＮＯ水平可以有效增加肾缺血再灌流后肾血流，改善肾功能，是防治ＩＡＲＦ又一新途径。     

乳腺良恶性病变组织c-met蛋白和转化生长因子α的表达及意义

应用免疫组化法测定５０例乳腺癌和１２例乳腺良性病变组织中ｃｍｅｔ蛋白及转化生长因子α（ＴＧＦα）的表达。结果：乳腺癌组织中ｃｍｅｔ蛋白及ＴＧＦα表达阳性率分别为２６．０％和４２．０％,乳腺良性病变组织中两者表达阳性率分别为８．３％和２５．０％;组织学分级为Ⅰ级,雌激素受体（ＥＲ）、孕激素受体（ＰＲ）及癌胚抗原（ＣＥＡ）为阴性的病例中,ｃｍｅｔ蛋白及ＴＧＦα表达阳性率明显低于组织学分级Ⅲ级,ＥＲ、ＰＲ及ＣＥＡ为阳性者（ｃｍｅｔ及ＰＲＰ＜０．０１;ＴＧＦα、ＰＲ和ＣＥＡＰ＜０．０５;余Ｐ＞０．０５）。本实验结果提示：ｃｍｅｔ蛋白及ＴＧＦα表达可能与乳腺癌发生发展及体机内分泌状态有较密切关系     

抗癌药物对乳腺癌细胞动力学及凋亡基因Bc1-2/Bax的影响

探讨抗癌药物对乳腺癌细胞动力学及凋亡基因Ｂｃｌ－２／Ｂａｘ的影响。方法用流式细胞术测定乳腺癌细胞核ＤＮＡ含量（ＤＩ）、Ｓ期细胞比率（ＳＰＦ）、细胞凋亡指数（ＡＩ）、凋亡基因Ｂｃｌ－２、Ｂａｘ的表达及雌激素受体（ＥＲ）等进行定量分析。结果①用药组与对照组相比,ＤＩ、ＳＰＦ及Ｂａｘ明显低于对照组（Ｐ＜０．０１）,而ＡＩ（Ｐ＜０．０５）、Ｂｃｌ－２（Ｐ＜０．００１）则高于对照组,ＥＲ于两组间无统计学差异;②ＡＩ与ＳＰＦ、Ｂｃｌ－２及ＥＲ的表达均呈正相关,而与Ｂａｘ无明显相关关系。结论抗癌药物主要通过细胞凋亡而发挥作用,用药后的生物学指标可表现为ＡＩ及Ｂｃｌ－２升高,ＳＰＦ、ＤＩ值及Ｂａｘ下降;ＡＩ与ＳＰＦ、Ｂｃｌ－２及ＥＲ均呈正相关。根据这些指标可判定药物的疗效,并可用于预后的预测。     

尿毒症患者红细胞变形能力与膜磷脂和收缩蛋白变化的关系

探讨尿毒症患者红细胞变形能力（ＥＤ）与红细胞膜磷脂成分和收缩蛋白的关系。方法检测了４８例尿毒症患者和４０例健康人红细胞滤过指数（ＩＦ）、红细胞膜磷脂成分和收缩蛋白二聚体（ＳＰ－Ｄ）和四聚体（ＳＰ－Ｔ）相对含量的变化。结果尿毒症患者红细胞ＩＦ明显高于对照组（Ｐ＜０．００１），膜磷脂成分中神经磷脂（ＳＭ）、磷脂酰胆碱（ＰＣ）、磷脂酰丝氨酸（ＰＳ）和磷脂酰乙醇胺（ＰＥ）明显低于对照组（Ｐ＜０．０１），而ＳＭ／ＰＣ高于对照组（Ｐ＜０．０５）；尿毒症患者红细胞ＳＰ－Ｄ和ＳＰ－Ｄ／ＳＰ－Ｔ明显增高，而ＳＰ－Ｔ明显减低，与对照组比较有显著性差异（Ｐ＜０．０１）。尿毒症患者红细胞ＩＦ与ＳＭ、ＰＣ、ＰＳ、ＰＥ和ＳＰ－Ｔ呈负相关（Ｐ＜０．０５，０．０１），与ＳＭ／ＰＣ、ＳＰ－Ｄ和ＳＰ－Ｄ／ＳＰ－Ｔ呈正相关（Ｐ＜０．０１）。结论尿毒症患者ＥＤ降低与红细胞膜磷脂和收缩蛋白异常有关     

TGFβ1及其I、II型受体在肾癌中的表达

目的探讨肾癌中转化生长因子β１（ＴＧＦβ１）及其Ｉ、Ｉ型受体（ＴＧＦβＲＩ、ＴＧＦβＲＩ）表达及其意义。方法采用免疫组化技术（ＳＰ法）对４６例肾癌,１１例正常肾组织ＴＧＦβ１、ＴＧＦβＲＩ、ＲＩ进行检测,结合临床资料进行分析。结果肾癌组ＴＧＦβ１表达量较正常肾组高（Ｐ＜０．０５）;ＴＧＦβＲＩ在肾癌组及正常肾组均表达;ＴＧＦβＲＩ在肾癌中阳性率较正常肾阳性率低（Ｐ＜０．０１）,ＴＧＦβＲＩ在高分期,高分级肾癌中表达阳性率较低分期、低分级肾癌低（Ｐ＜０．０５）;ＴＧＦβ１表达量低及ＴＧＦβＲＩ表达阴性肾癌者预后差。结论ＴＧＦβ１对肾癌是一种重要负性调节因子,可抑制肾癌进展,ＴＧＦβＲＩ缺失使ＴＧＦβ系统完整性受到破坏,ＴＧＦβ１失去负性调节作用。ＴＧＦβ１及ＴＧＦβＲＩ表达可做为判断肾癌预后的指标之一     

丹参及血栓通注射液对缺血再灌注大鼠肾脏的影响

丹参及血栓通注射液对缺血再灌注大鼠肾脏的影响徐幼筠，杜学海，邹万忠ＴＨＥＥＦＦＥＣＴＯＦＳＡＬＶＩＡＥＭＩＬＴＩＯＲＲＨＩＺＡＥ（ＳＭ）ＡＮＤＡＲＡＳＡＰＯＮＩＮ（ＡＲ）ＯＮＩＳＣＨＥＭＩＡ－ＲＥＰＥＲＦＵＳＩＯＮＲＡＴＫＩＤＮＥＹＸｕＹｏｕｊｕｎ；...     

颈髓损伤后内皮皮及其受体mRNA表达与血脊髓屏障损害的关系

目的：为了探讨颈髓损伤后内皮素－１（ＥＴ－１）ｍＲＮＡ、内皮素受体－Ａ（ＥＴＲ－Ａ）ｍＲＮＡ与血脊髓屏障损害的关系。方法：应用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）检测颈髓损伤后颈髓组织ＥＴ１ｍＲＮＡ、ＥＴＲ－ＡｍＲＮＡ表达,观察伤后血脊髓屏障通透性变化。结果：伤后６～７２ｈ颈髓组织ＥＴ１ｍＲＮＡ、ＥＴＲ－ＡｍＲＮＡ均较对照组明显增高（Ｐ〈０．０１）。伤后６～７２ｈ颈髓组织伊文思蓝含量、水含量呈不同程     

慢性肾功能衰竭患者血浆心钠素和肾素,血管紧张素II.醛固酮变化…

本文用ＲＩＡ法测定了３０例健康人、ＣＲＦ２４例非透析病人和１４例血透病人的血浆ＡＮＰ，ＰＲＡ，ＡＴⅡ，ＡＬＤ水平。结果表明ＣＲＦ病人ＡＮＰ，ＰＲＡ，ＡＴⅡ，ＡＬＤ明显高于对照组（Ｐ＜０．０５～０．０１），其中高血压组ＡＮｐ明显高于非高血压（Ｐ＜０．０５），血透后ＡＮＰ明显下降（Ｐ＜０．０１），ＡＮＰ和Ｓｃｒ，ＭＡＰ呈正相关，ＡＮＰ，ＡＴⅡ均和Ａ呈负相关，结合文献初步探讨了ＣＲＦ时，ＡＮＰ和ＰＡＳ的     

内皮素受体拮抗剂联合内皮源血管松弛因子防治大鼠缺血性急性肾衰竭

目的:观察内皮素受体拮抗剂PD145065联合内皮源血管松驰因子NO生理性前体L-arginine对大鼠缺血性急性肾衰竭是否有防治作用.方法:采用阻断大鼠双侧肾脏血流45 min再灌注24 h之急性肾缺血再灌注动物模型,观察内皮素受体拮抗剂PD145065或内皮源血管松驰因子NO生理性前体L-arginine或两者联合应用,对再灌注24 h后大鼠肾组织病理变化和肾功能的影响.结果:PD145065或L-arginine单独作用均可明显减轻肾缺血再灌注后的肾组织病理损害,提高肾小球滤过率,改善肾功能.其中,两者联合应用的效果比单独使用的效果更好.结论:缺血性急性肾衰竭时,内皮素升高及其受体上调是缺血性急性肾衰竭发生发展的重要因素,外源性给予内皮素受体拮抗剂可阻断内皮素的生物作用,并且联合内皮源血管松弛因子的应用效果更佳.这是防治缺血性急性肾衰竭的又一新途径.     

川芎嗪预防急性缺血性肾衰竭的实验研究

目的:探讨川芎嗪对大鼠急性缺血性肾衰竭(IARF)的保护作用及其可能的作用机制.方法:采用同时钳夹双侧肾动脉45 min,再灌注24 h建立大鼠IARF的动物模型,设立假手术组、造模组及川芎嗪预防组.观察各组大鼠血肌酐(Scr)、血清尿素氮(BUN)、血清一氧化氮(NO)、血清内皮素(ET)及肾脏病理的变化.结果:与造模组比较,川芎嗪预防组的Scr、BUN及ET水平明显降低(P<0.05),血清NO明显升高(P<0.05).结论:川芎嗪能减轻IARF的肾脏损害,对肾脏有保护作用,其机制可能与调节ET的分泌及血清NO的浓度有关.     

Influence of acute selective endothelin-receptor-A blockade on renal hemodynamics in a rat model of chronic allograft rejection

We have recently demonstrated up-regulation of renal endothelin (ET) synthesis in a rat model of chronic renal allograft rejection. Treatment with a selective ET-A receptor antagonist improved survival and reduced functional and morphological kidney damage. However, the underlying mechanisms have not yet been elucidated, as ET exhibits both hemodynamic and inflammatory properties. Therefore, in the present study we investigated acute hemodynamic effects of the selective ET-A receptor antagonist LU 302146 (LU) on chronic renal allograft rejection in rats. Experiments were performed in the Fisher-to-Lewis model of chronic renal allograft rejection. Lewis-to-Lewis isografts served as controls. After 2, 12, and 24 weeks, hemodynamic measurements were performed on anesthetized animals. Measurement of mean arterial pressure (MAP) was performed via a catheter in the femoral artery. Renal blood flow (RBF) was measured by an ultrasonic flow probe placed around the renal transplant artery. Medulla blood flow (MBF) and cortex blood flow (CBF) were determined with laser Doppler probes. Hemodynamic response upon intravenous bolus injection of LU (50 mg/kg) was investigated. The application of LU was followed by a decline in MAP that reached statistical significance only in isografts (ISOs) after 12 weeks and allografts (ALLOs) after 24 weeks. RBF slightly decreased in all groups; however, without reaching statistical significance. MBF showed a small increase in ALLO12 and ALLO24 whereas CBF slightly decreased in all groups. Acute ET-A receptor blockade does not induce important hemodynamic effects in kidneys undergoing chronic rejection. The lack of response to ET-A receptor blockade suggests that the beneficial effect of ET receptor antagonists in this model is likely to be due to improvement of renal morphology.     

Insulin-like growth factor I administration in young rats with acute renal failure

The outcome of ischemic acute renal failure (IARF) is better in young than adult rats. Insulin-like growth factor I (IGF-I) treatment may increase mortality of adult rats with IARF, probably because of an exaggerated inflammatory response. We report the response to IGF-I therapy in young rats with IARF. Male rats, aged 28+/-1 days, with IARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (IGF) or were untreated (ARF). Sham-operated rats were used as controls. At 2 and 7 days after ischemia, serum urea nitrogen and histological damage score, cell proliferation, apoptosis, neutrophil infiltration, and IGF-I receptor mRNA in kidneys were analyzed. The degree of renal failure, mortality rate, histological damage, cell proliferation, and neutrophil infiltration were not different between IGF-I and ARF rats. Hence, short-term IGF-I treatment did not modify the course of IARF in young rats.     

Beneficial effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure in the rat.

To determine the effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure (IARF), that disorder was induced in male Wistar rats. After the animals were anesthetized with sodium pentobarbital (50 mg/kg, i.p.), the right kidney was removed and the left renal pedicle was clamped for 60 min. DBcAMP (5 mg/kg, i.p.) was given each 30 min before and after the renal pedicle clamping in half the dose each. Twenty-four hours after surgery, the levels of serum creatinine, BUN, serum potassium, and FENa% were significantly less elevated; and the total urine volume was significantly less decreased for 24 h in the group of IARF given DBcAMP than in the group of IARF alone. The elevation in Ca2+ content of the renal cortex was also significantly lower in the group of IARF given DBcAMP than in the group of IARF alone. These data indicate that DBcAMP can produce a beneficial effect on experimentally induced IARF. Since the intracellular accumulation of Ca2+ has been reported to be a potentially harmful factor in the development of IARF, it is suggested that the effect of DBcAMP on IARF can be in part due to an inhibition of the intracellular accumulation of Ca2+ in the kidney.     

大鼠烧伤早期各内脏内皮素的变化

探讨烧伤后内皮素变化及其在骨脏损害中的应用。方法采用大鼠３０％Ⅲ度烧伤模型动态观察大鼠烧伤后血浆，心，肝，肺，肾脏内皮素的变化规律及应用非选择造反性内皮素受体拮抗剂ＰＤ１４５０６５对烧伤大鼠内脏损害的作用。     

Effects of radical scavengers and antioxidant on ischemic acute renal failure in rabbits

This study was undertaken to determine whether reactive oxygen species (ROS) are involved in the pathogenesis of ischemic acute renal failure (IARF) in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with combination of xanthine oxidase inhibitor (allopurinol), hydrogen peroxide scavenger (catalase), and hydroxyl radical scavenger (sodium benzoate). Serum creatinine level significantly increased 24 h after ischemia and remained higher to 72 h. Ischemia caused a reduction of GFR and an increase of FENa. Such changes were significantly attenuated by scavenger pretreatment. The uptake of p-aminohippurate in cortical slices and microsomal Na(+)-K(+)-ATPase activity were depressed in kidneys subjected to 72 h of reflow following ischemia, indicating impairment of tubular transport function, which were significantly attenuated by scavenger treatment. Renal blood flow 72 h after reflow was markedly reduced and it was restored by scavenger pretreatment. When animals were pretreated with a potent antioxidant DPPD, lipid peroxidation in cortex and medulla was significantly inhibited. However, ischemia-induced impairment of renal function was not attenuated by pretreatment of the antioxidant. These results suggest that radical scavengers may exert a protective effect against ischemia acute renal failure by other actions rather than ROS scavenging. Thus, the data do not support involvement of ROS in IARF in rabbits.     

Prevention of chronic renal allograft rejection in rats with an oral endothelin A receptor antagonist.

BACKGROUND: Chronic rejection is the most common cause of graft loss in renal transplantation. The pathomechanisms underlying chronic rejection are poorly understood, and no treatment has yet successfully been established. We hypothesized that, in analogy to models of reduced renal mass, the administration of a selective endothelin (ET) A receptor antagonist could improve the course of chronic rejection in renal allografts. METHODS: Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-->Lewis isografts served as controls. Animals were treated with either the oral selective ET-A receptor antagonist LU135252 (50 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light microscopical evaluation, determination of ET mRNA expression and tissue protein concentration, and immunohistochemical assessment of cell surface markers. RESULTS: Rats with chronic rejection showed an increase in renal ET mRNA synthesis and ET protein content. Treatment with LU135252 resulted in a significant improvement in survival after 24 weeks (0.92 vs. 0.38, P<0.01 by log-rank test). Creatinine clearance was higher in animals treated with the selective ET-A receptor antagonist (P<0.05). LU135252 had no influence on blood pressure and proteinuria. Selective ET-A blockade was associated with significantly less morphological changes and a significant reduction of expression of cell surface markers for macrophages (ED1), T cells (R73), and MHC II (F17-23-2). CONCLUSION: The renal ET-A system plays an important role in the pathomechanisms underlying chronic renal allograft rejection, because the treatment with a selective ET-A receptor antagonist dramatically improves the course of chronic renal failure after allograft transplantation. These results offer a novel therapeutical option for treatment of chronic renal allograft rejection, for which so far no therapy is known.     

Improved recovery following posttransplant acute renal failure in rat renal isografts with an oral endothelin-A receptor antagonist

BACKGROUND: Delayed renal function after transplantation is a strong predictor of long-term graft survival. As an increased expression of endothelin (ET) has been demonstrated during ischemia/reperfusion injury, we hypothesized that ET-A receptor blockade could improve the recovery of acute renal failure in a rat model of isogeneic kidney transplantation. METHODS: Kidneys of Fisher (F344, RT1(1v1)) rat donors flushed with cooled University of Wisconsin solution were transplanted into bilaterally nephrectomized Fisher rats. Recipient animals were treated orally either with vehicle or the selective ET-A receptor antagonist LU135252 (30 mg/kg/day p.o.) for 14 days. Unilaterally nephrectomized Fisher rats not subjected to ischemia served as controls. No immunosuppression was given. On days 2, 6 and 14, metabolic studies were performed to evaluate endogenous creatinine clearance, fractional sodium excretion, and urinary endothelin excretion. Kidneys were harvested at the end of the experiment for determination of renal ET content and immunohistochemical assessment. RESULTS: Urinary ET excretion was increased in vehicle-treated isografts compared to uninephrectomized controls after 14 days. Treatment with LU135252 resulted in a significant improvement in creatinine clearance and fractional sodium excretion to the level of uninephrectomized rats after 14 days. Isografts treated with selective ET-A receptor blockade demonstrated a marked reduction in cell surface markers for macrophages/monocytes, T cells, MHC-II, and ICAM-1. CONCLUSION: Treatment with the selective ET-A receptor antagonist LU135252 accelerates recovery of renal function after isogeneic renal transplantation and attenuates cellular graft infiltration. This effect could have major implications for the treatment of patients undergoing renal transplantation, as an improved initial renal function may delay the onset of chronic allograft rejection.