周围神经挤压伤后纤溶成分表达的变化

目的 观察大鼠坐骨神经挤压伤后纤溶成分中组织型纤溶酶原激活剂（ｔ－ＰＡ）和纤溶酶原激活剂抑制因子１（ＰＡＩ－１）蛋白表达的变化,了解ｔ－ＰＡ、ＰＡＩ－１在周围神地操作后修复过程中的作用。方法 取２１只Ｗｉｓｔａｒ大鼠,分别造成坐骨神经挤压伤模型。在术后６ｈ、１ｄ、３ｄ、７ｄ、１４和２１ｄ分别取材进行组织学、免疫组化观察。结果 术后３ｄ时神经断端回缩球处的ｔ－ＰＡ抗原呈阳性反应。７ｄ时损伤进行组织学     

重组组织型纤溶酶原激活剂对机体凝血酶原时间和纤维蛋白含量的影响

我们应用重组组织型纤溶酶原激活剂（ｒｔＰＡ）治疗下肢深静脉血栓形成患者１２例，并对其凝血酶原时间（ＰＴ）及纤维蛋白含量（ＦＩＢ）进行检测，以了解该激活剂对二者的影响。１对象与方法１．１研究对象本组１２例患者，男９例，女３例，年龄３３～７７岁，平均５...     

苦参碱对降低早期糖尿病肾病尿蛋白的作用

目的探讨苦参碱注射液防治早期糖尿病肾病的疗效及作用机制。方法将87例早期糖尿病肾病患者随机分为对照组（42例，口服糖适平，30mg／次、每日3次），治疗组（45例，在对照组的基础上静滴苦参碱氯化钠注射液100ml（含苦参碱80mg）、每日1次），连续观察21d。结果治疗组血清的组织型纤溶酶原激活剂（t-PA）／纤溶酶原激活剂抑制物（PAI-1）的活性、全血粘度、血浆粘度、纤维蛋白原、血清TG、TCH、LDI，C、24h尿蛋白定量、尿白蛋白排出率、肾功能都明显改善，与对照组比较差异具有统计学意义；对照组只有低切全血粘度有明显改善。结论苦参碱注射液可通过调节t-PA／PAI-1的活性、降低血脂、血粘度改善肾脏微循环和肾功能，减少尿蛋白，从而发挥对肾脏的保护作用。     

人正常胚胎和葡萄胎绒毛中纤蛋白溶酶原激活与抑制因子及其尿激酶？…

本研究应用原位杂交技术检测人正常胚胎及葡萄胎绒毛中纤蛋白溶酶原激活与抑制因子（ｔＰＡ，ｕＰＡ，ＰＡＩ－１）及其尿激酶受体（ｕＰＡ－Ｒ）的表达。结果表明，人正常胚胎绒毛的合体滋养层和细胞滋养层细胞中均含有ｔＰＡ、ｕＰＡ、ＰＡＩ－１及ｕＰＡ－Ｒ ｍＲＮＡ，葡萄胎绒毛中ｔＰＡ、ＰＡＩ－１及ｕＰＡ－Ｒ ｍＲＮＡ表达明显增强。提示：（１）ＰＡ－ＰＡＩ的协同作用在维持妊娠期间正常的纤蛋白溶解可能是重要的；（２     

人正常胚胎和葡萄胎绒毛中纤蛋白溶酶原激活与抑制因子及其尿激酶受体的表达

本研究应用原位杂交技术检测人正常胚胎及葡萄胎绒毛中纤蛋白溶酶原激活与抑制因子（ｔＰＡ,ｕＰＡ,ＰＡＩ－１）及其尿激酶受体（ｕＰＡ－Ｒ）的表达。结果表明,人正常胚胎绒毛的合体滋养层和细胞滋养层细胞中均含有ｔＰＡ、ｕＰＡ、ＰＡＩ－１及ｕＰＡ－ＲｍＲＮＡ,葡萄胎绒毛中ｔＰＡ、ＰＡＩ－１及ｕＰＡ－ＲｍＲＮＡ表达明显增强。提示：（１）ＰＡ－ＰＡＩ的协同作用在维持妊娠期间正常的纤蛋白溶解可能是重要的;（２）纤溶激活与抑制在葡萄胎的发展过程中可能起作用     

肢体负压对后肢动脉闭塞犬纤溶酶原激活物及其抑制因子1？…

目的 探讨肢体负压对犬纤溶系统的影响。方法 通过建立后肢动脉闭塞犬模型，检测肢体负压（ＬＮＰ）前后外周血纤溶酶原激活物（ｔ－ＰＡ）及其抑制物（ＰＡＩ－１）活性、静脉血氧分压（ＰＯ２）和ＰＨ值的变化。结果 ＬＮＰ治疗后实验组ｔ－ＰＡ活性、ＰＯ２、ＰＨ值较治疗前明显升高，ＰＡＩ－１活性显著下降（Ｐ〈０．０１），与对照组比较也有显著性差异（Ｐ〈０．０１）。结论 ＬＮＰ可提高局部纤溶活性，促进血栓溶解和再     

倍美力对绝经后妇女纤溶活性的影响

为了探讨激素替代治疗（ＨＲＴ）的心血管保护机制，观察了倍美力对绝经后妇女纤溶活性的影响。４８例绝经后妇女分为３组：安慰剂组１０例；单用倍美力组（Ｅ组）１７例；倍美力、孕激素合用组（Ｅ＋Ｐ组）２１例，并以２０例绝经前妇女作为对照。采用发色底物法测定了ＨＲＴ治疗前及治疗３个月后血浆组织纤溶酶原激活剂（ｔＰＡ）及其抑制因子（ＰＡＩ）活性。结果：绝经后妇女治疗前ＰＡＩ活性明显高于对照组（Ｐ＜０．０１）。安慰剂组治疗前后ｔＰＡ及ＰＡＩ均无显著性变化（Ｐ＞０．０５）。Ｅ及Ｅ＋Ｐ组治疗３个月后ＰＡＩ活性明显减低，ｔＰＡ活性明显升高（Ｐ＜０．０１），两组比较，治疗前后ｔＰＡ及ＰＡＩ活性均无显著性差异。认为ＨＲＴ可通过改善绝经后妇女纤溶活性保护心血管。     

纤溶酶原激活及抑制因子在人蜕膜腺体与间质细胞中的生成及调节

为了探讨人早孕蜕膜腺体与间质细胞离体培养下释放活性纤蛋白溶酶原激活及抑制因子（ＰＡ，ＰＡＩ）的平衡关系与激素调节。应用琼脂糖纤蛋白铺盖及反向铺盖技术，测得腺体及间质细胞均仅释放尿激酶型ＰＡ（ＵＰＡ），而不释放组织型ＰＡ（ｔＰＡ），并同时生成Ⅰ型ＰＡ抑制因子（ＰＡＩ－１）。雌二醇（Ｅ２）及ＲＵ４８６刺激ｕＰＡ、抑制ＰＡＩ－１活性，孕酮（Ｐ）的作用则相反，提示Ｐ在人早孕蜕膜中的作用之一是使ＰＡ－ＰＡ１的动态平衡趋于纤溶活性受抑的安静状态，而ＲＵ４８６激活蜕膜纤溶过程，从而增强细胞外基质蛋白水解，可能是其抗早孕作用机理之一。     

消栓通脉合剂对深静脉血栓形成纤溶功能的影响

目的：观察消栓通脉合剂对深静脉血栓形成溶功能的影响。方法：结扎大鼠下腔静脉复制深静脉血栓形成模型。观测消栓通脉合剂对组织型纤溶酶原活化剂（ｔ－ＰＡ）活性、纤溶酶原活化剂抑制物（ＰＡＩ）活性、血栓干重的影响。结果：消栓通脉合剂治疗组明显提高ｔ－ＰＡ、降低ＰＡＩ和血栓干重，与通塞脉片对照组比较，ＰＡＩ和血栓干重有显著性差异。预防组与生理盐水对照组比较，ｔ－ＰＡ、ＰＡＩ和血栓干重均有显著性差异。结论：消     

乳腺癌患者的组织型纤溶酶原激活剂及其抑制剂检测的意义

我们采用发色底物法测定乳腺癌和乳腺纤维腺瘤组织中的组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活剂抑制剂-1(PAI-1)活性.旨在了解这二者与乳腺癌各病理参数及激素受体之间的关系.并探讨其在乳腺癌中的作用和意义.     

Glomerular basement membrane metabolism in the diabetic rat. In vivo studies.

The effect of diabetes on the metabolism of the renal glomerular basement membrane has been studied in the rat with the aid of injected tracer doses of tritiated proline. At various times after administration of the labeled amino acid, the specific radioactivities of the proline and hydroxyproline of the basement membranes from alloxan diabetic rats were determined and compared with those of age-matched normal rats. In both normal and diabetic animals the incorporation of radioactivity into the basement membrane was slow and, after a maximum was reached, an extended period of almost constant specific activity of proline and hydroxyproline was observed. The diabetic basement membrane, however, differed from the normal by attaining specific activities of the amino acids which were about twice as high as normal (P less than 0.001 at 42 h after injection of radioisotope). Although the proline concentration of serum and renal cortical fluid was the same in normal and diabetic rats, there were substantial differences in the specific activity of this precursor amino acid in these pools that had to be taken into account to compare the two types of animals. The results of the present study are consistent with an accelerated rate of glomerular basement membrane polypeptide synthesis and proline hydroxylation in diabetes.     

Non-enzymatic glycation and altered renal structure and function in the diabetic rat

Renal functional parameters including creatinine clearance, urinary albumin excretion, basement membrane thickening, and levels of non-enzymatic glycation of glomerular basement membrane were studied in rats rendered diabetic with streptozotocin. Diabetic animals had elevated, glycated hemoglobin levels (P less than 0.05), increased creatinine clearance, and urinary albumin excretion rates (P less than 0.05) as compared to insulin treated diabetic (euglycemic), age-matched, and streptozotocin non-diabetic animals. The level of non-enzymatic glycation of glomerular basement membrane was significantly elevated (P less than 0.05) in the diabetic animals as well, with the level of non-enzymatic glycation of all animals, correlating (P less than 0.05) to the average blood glucose level of each animal. Despite changes in functional parameters, and increased levels of non-enzymatic glycation between the diabetic and euglycemic animals, there was no difference in glomerular basement membrane thickness between the two groups. However, there was a difference between all diabetic euglycemics and the age-matched control animals. We hypothesize that increased glycation of glomerular basement membrane may alter renal function, possibly by affecting the net charge of the glomerular filtration barrier. However, glomerular basement membrane thickening per se does not affect the functional changes which have been observed, thus casting doubt upon its role in the development of diabetic nephropathy.     

Insulinlike effects of sodium selenate in streptozocin-induced diabetic rats.

Treatment of streptozocin (STZ)-induced diabetic rats with sodium selenate (10-15 mumol.kg-1.day-1) for 7 wk resulted in a decrease in plasma glucose, food intake, and water intake to control or near control levels. Plasma insulin was reduced in control rats given sodium selenate to the level found in the diabetic and treated diabetic group. Treatment did not affect control rats with regard to the other measurements cited. Sodium selenate enhanced weight gain in responding diabetic rats to that seen in controls; sodium selenate's actions thus resembled those of insulin. Thus selenate, like vanadium, appears to have insulinlike effects when administered in vivo.     

Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats.

Abnormal glycosaminoglycan metabolism is involved in the onset of anatomo-functional derangements in diabetic nephropathy, and determines the loss of glomerular basement membrane anionic charges leading to albuminuria. Glycosaminoglycan administration was shown to increase the negative electrical potential of the vessel wall, inhibit mesangial cell proliferation, which is an anatomical hallmark of diabetic nephropathy, and slow down the progression to uremia in subtotally nephrectomized rats, a model that shares some pathogenetic key events with diabetic nephropathy. Based on these considerations, we verified the effect of exogenous glycosaminoglycans on renal involvement in streptozotocin diabetic rats. Long-term administration of two glycosaminoglycans (low-molecular weight heparin and dermatan sulphate) prevented glomerular basement membrane thickening, glomerular anionic charge reduction, as well as the onset of albuminuria without affecting glomerular filtration rate and metabolic control of the disease. Our data demonstrate that the long-term administration of glycosaminoglycans has a favorable effect on morphological and functional renal abnormalities in diabetic rats.     

Decreased glomerular proteinase activity in the streptozotocin diabetic rat.

Decreased glomerular proteinase activity may contribute to matrix accumulation in diabetes. Male Sprague-Dawley rats were rendered diabetic by injection of streptozotocin (STZ) 65 mg/kg i.v.; age-matched, sham-injected rats served as controls. Glomeruli from diabetic rats 1 month after STZ injection demonstrated significant decreases in collagenase and cathepsin B activities compared to control glomeruli. Treatment with insulin resulted in a slight (but not significant) increase in collagenase activity and normalized cathepsin B activity. We conclude that decreased glomerular collagenase and cathepsin B activities are present in STZ diabetes. These alterations may contribute to mesangial matrix accumulation.     

Expression and localization of MT1-MMP and furin in the glomerular wall of short- and long-term diabetic rats

Diabetic glomerulopathy has been linked to shifts in balance between the synthetic and degradative pathways of the glomerular basement membrane (GBM), a key player in the permselectivity properties of the glomerular wall. The goal of this study was to trace the expression and localization of membrane type-1 metalloprotease (MT1-MMP) and its activating enzyme furin, key proteins involved in basement membrane turnover, in short- and long-term diabetic rat renal tissues. Quantitative immunogold was carried out for MT1-MMP and furin and their expression was evaluated in renal tissues of young and old, control and diabetic rats. To corroborate immunocytochemical findings, Western blots were performed on glomerular lysates. Electron microscopy revealed that the overall expression of MT1-MMP and furin is reduced in plasma membranes of all glomerular cell types of old normoglycemic animals, a phenomenon that is exacerbated in long-term diabetic animals. This observation supports the prevailing theory that diabetes fosters acceleration in the aging process. Interestingly, while biochemical results confirmed a decrease in MT1-MMP expression, an increase in furin was observed. Immunocytochemical studies resolved this discrepancy by tracing the increased furin expression in endoplasmic reticulum and Golgi membranes of podocytes, indicating that furin is retained in the secretory pathway in a diabetic environment. Disturbances at the molecular level of the otherwise tightly regulated MT1-MMP/furin interactions found at the cell surface must account for a lack in extracellular matrix remodeling, increased deposition of GBM material, and loss of glomerular filtration integrity.     

氟伐他汀对糖尿病肾病中脂蛋白(a)水平的影响

目的：探讨氟伐他汀对糖尿病肾病中脂蛋白（a)水平的影响及其肾脏保护作用。方法：分别以糖尿病大鼠模型和2型糖尿病肾病患为研究对象，观察氟伐他汀治疗6周后血浆中脂蛋白（a)水平，组织型纤溶酶原激活物及其抑制剂活性，大鼠肾脏病理学改变。结果：与对照组比较，氟伐他汀治疗6周后糖尿病肾病患和大鼠体内脂蛋白（a)，尿白蛋白水平均降低，患纤溶酶原激活物抑制剂活性下降，纤溶酶原激活物活性上升，大鼠肾脏组织光镜及电镜下病变明显减轻。结论：氟伐他汀能下调脂蛋白（a)，减轻肾脏肥大，具有肾脏保护作用。     

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。     

Prevention of albuminuria by aminoguanidine or ramipril in streptozotocin-induced diabetic rats is associated with the normalization of glomerular protein kinase C

This study examined whether the prevention of diabetes-related albuminuria by aminoguanidine (AG) or ramipril (RAM) may be mediated by a common post-glomerular basement membrane renal intracellular mechanism involving protein kinase C (PKC). The renal handling of albumin was examined over 24 weeks in control and streptozotocin (STZ)-induced diabetic rats. A radioimmunoassay (RIA) that measures intact albumin, and intravenously injected tritium-labeled rat serum albumin, was used to assess the proportion of intact albumin and albumin fragments in urine. Diabetes was induced in male Sprague-Dawley rats by the intravenous administration of STZ at a dose of 50 mg/kg. Age-matched control rats received buffer alone. Diabetes was characterized by an increase in blood glucose (>15 mmol/l), an increase in GHb (means at 24 weeks 29.3+/-1.1%; control 6.1+/-0.1%, P<0.005), an increase in glomerular filtration rate (GFR) (4.13+/-0.15 ml/min; control 3.54+/-0.19 ml/min, P<0.005), an increase in intact albumin excretion rate (expressed as geometric mean 11.64 times/divided by 2.11 mg/24 h; control 0.74 times/divided by 1.57 mg/24 h, P<0.005) as measured by RIA, and an increase in glomerular PKC activity (26.83+/-2.38 pmol x mg(-1) x min(-1); control 14.6+/-2.99 pmol x mg(-1) x min(-1), P<0.005). Treatment of diabetic rats with either AG or RAM prevented the rise in intact albuminuria and glomerular PKC activity. Renal lysosomal cathepsin activity decreased in diabetic rats and this was not prevented by AG or RAM. Neither drug affected glycemic control or GFR, but RAM reduced systolic blood pressure (BP), whereas AG did not. These data indicate that urinary excretion of intact albumin and albumin-derived fragments in diabetes may be modulated independently of glycemic control (AG and RAM) and systolic BP (RAM). While both drugs are known for their different mechanisms of action, the fact that both prevent diabetes-related increases in glomerular PKC activity and albuminuria supports the hypothesis that PKC plays a central role in the development of diabetic nephropathy.     

Altered glomerular mRNA expression of basement membrane components and type I collagen in diabetic rats treated with or without insulin therapy

Glomerular basement membrane (GBM) thickening has been reported to be a characteristic change of diabetic nephropathy. Previous studies of GBM in animal models of diabetes indicated that there are no consensus in the alteration of synthesis of GBM component. The aim of this study was to determine whether the glomerular mRNA levels encoding type I and type IV collagen. B1 laminin, and heparan sulfate proteoglycan (HSPG) are altered in streptozotocin diabetic rats with or without insulin therapy. Glomerular mRNA levels for type I and type IV collagen, laminin B1, were significantly increased, but that for HSPG were marked decreased in 4 week diabetic rats compared with age-matched control rats. Insulin therapy has normalized these abnormally regulated gene expressions. Renal morphology shows no significant changes between 4 weeks diabetic rats and age-matched control rats. These results indicate that abnormal gene expressions of BM components and type I collagen might play an important role in the initiation of glomerular changes in diabetes.