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尿大分子与肾小管细胞免受草酸损伤的保护作用:正常受试者与复发性结石形成者的比较。

Urinary macromolecules and renal tubular cell protection from oxalate injury: comparison of normal subjects and recurrent stone formers.

作者信息

Tsujihata Masao, Tsujikawa Kozo, Tei Norihide, Yoshimura Kazuhiro, Okuyama Akihiko

机构信息

Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Int J Urol. 2006 Mar;13(3):197-201. doi: 10.1111/j.1442-2042.2006.01271.x.

Abstract

AIM

To determine whether urinary macromolecules (UMM), which are the high molecular weight substances in urine, can provide protection against the oxalate-associated injury to the renal tubular cells.

METHODS

UMM were extracted from 24-h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male patients. Urine parameters in relation to urolithiasis were measured, including the level of glycosaminoglycans (GAG) in the UMM. Madin-Darby canine kidney (MDCK) cells were used to evaluate the protective activity of UMM from oxalate-induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium (MTT) assay.

RESULTS

Considering urinary parameters, citrate was significantly higher in urine from normal subjects than stone-former subjects; the other parameters show no differences between the groups. Total UMM and the level of GAG in the UMM were also significantly higher in the normal subject group. Compared with normal subject and stone-former subject UMM, after cells were treated with the UMM and then exposed to oxalate solution, LDH release was significantly higher in stone-former group. In the MTT assay, we found that more viable cells were observed after treatment with UMM compared to control in both groups. Moreover, UMM from the normal subjects showed higher protective activity against oxalate-related cytotoxicity than UMM from the stone-former subjects.

CONCLUSION

UMM protected renal epithelial cells from oxalate-related injury. This protective activity was found to be higher in normal subject UMM than stone-former UMM. Among other factors, a higher concentration of GAG and citrate in normal subject UMM might affect some parts in this finding.

摘要

目的

确定尿中大分子物质(UMM,即尿液中的高分子量物质)是否能对草酸相关的肾小管细胞损伤起到保护作用。

方法

从12名健康成年男性志愿者和13名复发性结石形成男性患者的24小时尿液中提取UMM。测量与尿石症相关的尿液参数,包括UMM中糖胺聚糖(GAG)的水平。使用麦迪逊-达比犬肾(MDCK)细胞,通过乳酸脱氢酶(LDH)释放测量和甲基噻唑基四氮唑(MTT)试验评估UMM对草酸诱导的细胞毒性的保护活性。

结果

考虑尿液参数,正常受试者尿液中的柠檬酸盐显著高于结石形成者;其他参数在两组之间无差异。正常受试者组中总UMM和UMM中GAG的水平也显著更高。与正常受试者和结石形成者的UMM相比,细胞用UMM处理后再暴露于草酸盐溶液,结石形成者组的LDH释放显著更高。在MTT试验中,我们发现两组中用UMM处理后观察到的活细胞均多于对照组。此外,正常受试者的UMM对草酸相关细胞毒性的保护活性高于结石形成者的UMM。

结论

UMM可保护肾上皮细胞免受草酸相关损伤。发现正常受试者的UMM的这种保护活性高于结石形成者的UMM。在其他因素中,正常受试者UMM中较高浓度的GAG和柠檬酸盐可能影响了这一发现的某些方面。

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