内质网应激在氟中毒大鼠肾损害中的作用

J4 ›› 2009, Vol. 35 ›› Issue (6): 992-995.

内质网应激在氟中毒大鼠肾损害中的作用

孙景春¹, 王春艳², 徐辉², 李广生²

（1. 吉林大学中日联谊医院检验科,吉林长春 130033； 2. 吉林大学再生医学研究所病理室,吉林长春 130021）

收稿日期:2009-06-09 出版日期:2009-11-28 发布日期:2009-11-28
通讯作者: 徐辉 E-mail:Tel：0431-85619287，E-mail：xuhui1010@sina.com
作者简介:孙景春（1966-）|男|吉林省德惠县人|副教授|医学硕士|主要从事医学检验和临床实验诊断研究
基金资助:
国家自然科学基金资助课题（30700688）

Effect of endoplasmic reticulum stress in renal injury of fluorosis rats

SUN Jing-Chun¹, WANG Chun-Yan², XU Hui², LI An-Sheng²

（1.Department of |Laboratory,China-Japan Union Hostipal,Jilin University,Changchun 130033,China;2. Department of Pathology,Institute of Frontier Medical Sciences,Jilin University,Changchun 130021,China）

Received:2009-06-09 Online:2009-11-28 Published:2009-11-28

摘要/Abstract

摘要：

目的：　初步观察内质网应激在氟中毒大鼠肾组织中的变化，探索内质网应激在氟中毒肾损伤机制中的作用。方法：　48只Wistar 大鼠按体重平均分成4组：常食对照组、常食加氟组、低钙对照组和低钙加氟组；分别给予常食和低钙饮食，加氟组大鼠饮水中投氟化钠（NaF）（221 mg•L-1）3个月。实验结束后，取一侧肾脏制作病理切片，在光镜下观察形态学变化。取各组大鼠50 mg肾组织抽提总RNA，利用RT-PCR技术分析内质网应激相关基因Grp78、Xbp1、CHOP和PDI的表达水平。结果：光镜下可见，常食加氟组大鼠肾组织以近端小管和远端小管上皮细胞水肿和空泡变性为主；低钙加氟组大鼠肾组织近端小管和远端小管上皮细胞呈现水肿和空泡变性，伴有散在的坏死、轻度再生修复和肾间质充血；常食对照组和低钙对照组大鼠肾组织无明显变化。RT-PCR产物经半定量分析显示，低钙加氟组和常食加氟组大鼠肾组织Xbp1的表达较相应对照组明显增强（P<0.05），低钙加氟组大鼠肾组织Grp78 mRNA表达较常食加氟组和低钙对照组明显增强（P<0.05或 P<0.01）；而低钙加氟组大鼠肾组织PDI的表达较常食加氟组明显下降（P<0.05）。各组大鼠肾组织CHOP表达差异无显著性（P>0.05）。结论：过量氟可造成肾组织损伤，低钙营养进一步加剧了氟对肾的损伤作用，而内质网应激很可能参与该损伤机制。

关键词: 氟化钠；肾脏；内质网应激

Abstract:

To observe the change endoplasmic reticulum stress in renal injury of fluorosis rats, and explore the effect of endoplasmic reticulum stree in the mechanism of renal injury of fluorosis.Methods 48 Wistar rats were divided into 4 groups:control,fluoride-treated,low calcium,and low calcium plus fluoride-treated.The rats in fluoride-treated and low calcium plus fluoride-treated groups were treated with sodium fluoride (NaF,221 mg•L-1) through drinking water for 3 months.The pathological slice of rat kidney was made and the morphological changes were observed under optical microscope.The transcription levels of Grp78,Xbp1,CHOP and PDI in the kidney ti
ssues were determined by reverse transcription-polymerase chain reaction (RT-PCR).Results Edema and vacuolar degeneration of the proximal tubule and distal tubule cells in the kidney tissues in fluoride-treated group were observed;and cell edema
,vacuolar degeneration,scattered necrosis,minor regeneration repair and interstitial hyperemia in the kidney tissues in low calcium plus fluoride-treated group were found
.The mRNA expressions of Xbp1 in the kidney tissues in fluoride-treated and low calcium plus fluoride-treated groups were markedly higher than that in the responding control groups（P<0.05）. The mRNA expression of Grp78 in the kidney tissues in low calcium plus fluoride-treated group was　significantly increased than that in fluoride-treated and low calcium groups（P<0.05 or P<0.01）.The mRN
A expression of PDI in the kidney tissues in low calcium plus fluoride-treated group was significantly decreased than that in fluoride-treated group （P<0.05）;there was no significant difference in CHOP expression in the kidney tissues among 4 groups.Conclusion Overdosal fluoride can induce renal injury,and low calcium nutrition may aggravate the toxicity of fluoride on kidney.Endoplasmic reticulum stress is likely involved in the pathogenesis of renal injury of fluorosis rats.

Key words: sodium fluoride;kidney;endoplasmic reticulum stress

中图分类号:

R599.9

孙景春, 王春艳, 徐辉, 李广生. 内质网应激在氟中毒大鼠肾损害中的作用[J]. J4, 2009, 35(6): 992-995.

SUN Jing-Chun, WANG Chun-Yan, XU Hui, LI An-Sheng. Effect of endoplasmic reticulum stress in renal injury of fluorosis rats[J]. J4, 2009, 35(6): 992-995.