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【文摘发布】又一个新发现!肾小球基底膜内硫酸乙酰肝素降解不会引起蛋白尿

In Vivo Degradation of Heparan Sulfates in the Glomerular Basement Membrane Does Not Result in Proteinuria



Heparan sulfates (HS) are long, unbranched, negatively charged polysaccharides that are bound to core proteins. HS in the glomerular basement membrane (GBM) is reported to be important for charge-selective permeability. Aberrant GBM HS expression has been observed in several glomerular diseases, such as diabetic nephropathy and membranous glomerulopathy, and a decrease in HS generally is associated with proteinuria. This study, with the use of a controlled in vivo approach, evaluated whether degradation of HS in rat GBM resulted in acute proteinuria. Rats received two intravenous injections of either heparinase III to digest HS or neuraminidase to remove neuraminic acids (positive control). Urine samples were taken at various time points, and at the end of the experiment, kidneys were removed and analyzed. Injection with heparinase III resulted in a complete loss of glomerular HS as demonstrated by immunofluorescence staining using anti-HS antibodies and by electron microscopy using cupromeronic blue in a critical electrolyte concentration mode. In the urine, a strong increase in HS was found within 2 h after the first injection. Staining for agrin, the major HS proteoglycan core protein in the GBM, was unaltered. No urinary albumin or other proteins were detected at any time point, and no changes in glomerular morphology were noticed. Injection of rats with neuraminidase, however, resulted in a major increase of urinary albumin and was associated with an increase in urinary free neuraminic acid. An increased glomerular staining with Peanut agglutinin lectin, indicative of removal of neuraminic acid, was noted. In conclusion, removal of HS from the GBM does not result in acute albuminuria, whereas removal of neuraminic acid does.

Tessa J.M. et al. J Am Soc Nephrol 18: 823-832, 2007
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In Vivo Degradation of Heparan Sulfates in the Glomerular Basement Membrane Does Not Result in Proteinuria
肾小球基底膜内硫酸乙酰肝素降解不会引起蛋白尿

Heparan sulfates (HS) are long, unbranched, negatively charged polysaccharides that are bound to core proteins. HS in the glomerular basement membrane (GBM) is reported to be important for charge-selective permeability. Aberrant GBM HS expression has been observed in several glomerular diseases, such as diabetic nephropathy and membranous glomerulopathy, and a decrease in HS generally is associated with proteinuria.
硫酸乙酰肝素(HS)是一种结合在核心蛋白上的带负电荷的长直链多糖。据报道,肾小球基底膜(GBM)内的硫酸乙酰肝素(HS)对于电荷选择通透性至关重要。一些肾小球疾病中曾见到异常肾小球基底膜硫酸乙酰肝素表达,如糖尿病性肾病变和膜性肾小球病,HS减少通常与蛋白尿有关。
This study, with the use of a controlled in vivo approach, evaluated whether degradation of HS in rat GBM resulted in acute proteinuria. Rats received two intravenous injections of either heparinase III to digest HS or neuraminidase to remove neuraminic acids (positive control). Urine samples were taken at various time points, and at the end of the experiment, kidneys were removed and analyzed.
本研究利用设置对照的体内技术评估了鼠GBM内HS降解是否引起急性蛋白尿。实验大鼠接受两次肝素酶III注射以消化HS,或两次神经氨酸酶注射以除去神经氨酸(阳性对照)。取不同时间点的尿液标本,实验结束时,取出鼠肾脏加以分析。
Injection with heparinase III resulted in a complete loss of glomerular HS as demonstrated by immunofluorescence staining using anti-HS antibodies and by electron microscopy using cupromeronic blue in a critical electrolyte concentration mode. In the urine, a strong increase in HS was found within 2 h after the first injection. Staining for agrin, the major HS proteoglycan core protein in the GBM, was unaltered. No urinary albumin or other proteins were detected at any time point, and no changes in glomerular morphology were noticed.
通过抗HS抗体免疫荧光染色和cupromeronic blue临界电解质浓度模式电镜检查证实注射肝素酶III可使肾小球HS完全丧失。第一次注射后2小时尿中HS明显增加。而GBM内主要的HS蛋白多糖核心蛋白—集聚蛋白(Agrin)染色没有变化。在任何一个时间点都没有检测到尿白蛋白或其它蛋白,肾小球形态也没有改变。
Injection of rats with neuraminidase, however, resulted in a major increase of urinary albumin and was associated with an increase in urinary free neuraminic acid. An increased glomerular staining with Peanut agglutinin lectin, indicative of removal of neuraminic acid, was noted. In conclusion, removal of HS from the GBM does not result in acute albuminuria, whereas removal of neuraminic acid does.
然而给大鼠注射神经氨酸酶却可以使尿白蛋白大量增加,并伴有尿液游离神经氨酸增加。实验中所观察到的肾小球花生凝集素染色增强标志着神经氨酸被清除。结论,从肾小球中除掉HS不会导致蛋白尿,但除掉神经氨酸则可以引起蛋白尿。

Tessa J.M. et al. J Am Soc Nephrol 18: 823-832, 2007

编译:

体内肾小球基底膜硫酸乙酰肝素降解不会引起蛋白尿。

硫酸乙酰肝素(HS)是一种结合在核心蛋白上的带负电荷的长直链多糖。据报道,肾小球基底膜(GBM)内的HS对于电荷选择通透性至关重要。GBM内HS表达异常曾见于某些肾小球疾病,如糖尿病肾病和膜性肾病,HS减少通常与蛋白尿相关。本研究利用设置对照的体内技术评价了大鼠GBM内HS降解是否会导致急性蛋白尿。实验大鼠接受两次肝素酶III注射以消化HS,或两次神经氨酸酶注射以除去神经氨酸(阳性对照)。在不同时间点收集尿液标本,实验结束时切除肾脏用于分析。通过抗HS抗体免疫荧光染色和cupromeronic blue临界电解质浓度模式电镜检查证实注射肝素酶III可使肾小球HS完全丧失。第一次注射后2小时尿中HS明显增加。而GBM内主要的HS蛋白多糖核心蛋白—集聚蛋白(Agrin)染色没有变化。在任何一个时间点都没有检测到尿白蛋白或其它蛋白,肾小球形态也没有改变。但是给大鼠注射神经氨酸酶却可以使尿白蛋白大量增加,并伴有尿液游离神经氨酸增加。实验中所观察到的肾小球花生凝集素染色增强标志着神经氨酸被清除。可得出结论,从肾小球中除掉HS不会导致蛋白尿,但除掉神经氨酸则可以引起蛋白尿。(丁香)
呵呵!你是从我的博客里找到本人译文的吗?
本人有些地方还没有弄清楚,比如下面一句到底是什么意思?
by electron microscopy using cupromeronic blue in a critical electrolyte concentration mode.
麻烦你或者其他战友查查资料给出这句话的确切含义,谢谢。
本来自己在翻译的,谁知碰到 cupromeronic blue in a critical electrolyte concentration mode不太明白,上百度一搜,竟然有现成已翻译好了的,于是就copy下来省事了。

我查了些文献好像cupromeronic blue 是用来给微量蛋白聚糖 和硫酸化葡萄糖胺聚糖染色常用制剂。

请其他战友补充说明,谢谢!!
呵呵,没关系,我的译文只要对园子里的战友有价值,copy好了。希望surgeond战友继续支持本版块的活动。
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