层粘连蛋白对单侧输尿管梗阻大鼠GRP78、GRP94表达的影响。

Cui Zhang, Jing Gao, Lan Zhang
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引用次数: 5

摘要

目的:研究层粘连蛋白对肾间质纤维化大鼠肾内质网分子伴侣蛋白(GRP78和GRP94)表达的影响。材料与方法:建立单侧输尿管梗阻(UUO)大鼠肾间质纤维化模型。将大鼠随机分为对照组、模型组、依那普利组、层次素高剂量组、层次素中剂量组和层次素低剂量组。术后第7天处死大鼠,采集血样。测定血清肌酐(SCr)和尿素氮(BUN)水平。苏木精、伊红染色测定肾小管损伤指数。采用Masson染色法测定肾间质纤维化胶原区百分比。Western blotting检测肾组织内质网应激(ERS)蛋白GRP78和分子伴侣GRP94的表达。结果:模型组与治疗组大鼠肾小管间质损伤指数、肾间质纤维化、SCr水平、BUN水平及GRP78、GRP94表达差异均有统计学意义(p < 0.01)。GRP78、GRP94在大鼠肾组织中的表达升高(p < 0.05)。与laminarin中剂量组相比,肾小管间质损伤和肾间质纤维化程度降低(p < 0.05),肾功能、SCr和BUN降低(p < 0.05)。结论:UUO在层粘胶蛋白作用后早期激活ERS反应,增加GRP78和GRP94的表达,促进变性蛋白的重折叠、组装和膜运输。从而阻断ERS信号转导通路,阻止细胞凋亡,减少肾间质纤维化的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of laminarin on the expression of GRP78 and GRP94 in rat after unilateral ureteral obstruction.

Objective: The objective of this study was to determine the effect of laminarin on the expression of kidney endoplasmic reticulum molecular chaperones (GRP78 and GRP94) in rats with renal interstitial fibrosis.

Material and methods: A renal interstitial fibrosis model in rats was developed by unilateral ureteral obstruction (UUO). Rats were randomly divided into control group, model group, enalapril group, laminarin high-dosage group, laminarin median-dosage group and laminarin low-dosage group. The rats were killed 7 days after surgery and blood samples were collected. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined. Renal tubular damage index was determined by hematoxylin and eosin staining. The percentage of areas with renal interstitial fibrosis collagen was determined by the Masson staining method. Expression of kidney tissue endoplasmic reticulum stress (ERS) protein GRP78 and molecular chaperone GRP94 was determined by Western blotting.

Results: Tubulointerstitial injury index, renal interstitial fibrosis, SCr level, BUN level and expressions of GRP78 and GRP94 were significantly different between the model group and treatment groups (p < 0.01). Expressions of GRP78 and GRP94 in rat nephridial tissue was increased (p < 0. 05), tubulointerstitial injury and renal interstitial fibrosis degree were decreased (p < 0.05) and renal function, SCr and BUN were decreased (p < 0.05) compared to those in the laminarin medium-dosage group.

Conclusions: The results demonstrate that UUO activated the reaction of ERS and increased the expression of GRP78 and GRP94 in the early period after laminarin was applied, which helped the refolding, assembling and membrane transportation of denatured proteins. Consequently, the ERS signal transduction pathway was blocked, apoptosis was prevented and the development of renal interstitial fibrosis was reduced.

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来源期刊
Scandinavian Journal of Urology and Nephrology
Scandinavian Journal of Urology and Nephrology 医学-泌尿学与肾脏学
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