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S100A9基因敲除对姥鲛烷诱导小鼠狼疮肾炎的影响OA北大核心CSTPCD

Effects of S100A9 knockout on pristane-induced lupus nephritis in mice

中文摘要英文摘要

目的:探究S100A9基因敲除(S100A9-/-)对小鼠狼疮性肾炎(lupus nephritis,LN)的影响,阐明S100A9在LN中的作用.方法:6~8周龄雌性野生型及S100A9-/-C57BL/6(B6)小鼠各10只;5只野生型B6和5只S100A9-/-B6小鼠一次性腹腔注射0.5 mL姥鲛烷;另外5只野生型B6和5只S100A9-/-B6小鼠一次性腹腔注射0.5 mL生理盐水.6个月后处死小鼠;ELISA法检测血清中抗双链DNA(double-stranded DNA,ds-DNA)抗体水平;测定血清肌酐、血清尿素氮、尿蛋白水平;留取肾组织进行HE染色,观察肾脏病理.结果:与野生型B6小鼠相比,S100A9-/-B6小鼠体重、脾脏重量、肾脏结构、血清肌酐水平等差异无统计学意义;与对照的B6小鼠相比,姥鲛烷诱导的B6小鼠脾脏重量、脾脏长度、血清肌酐、尿素氮、尿蛋白、抗ds-DNA抗体、IgG水平均明显增加,肾脏出现狼疮样改变(肾脏肾小球体积增大,肾小管上皮水肿、管腔狭窄);与对照S100A9-/-B6小鼠相比,姥鲛烷诱导的S100A9-/-B6小鼠脾脏重量、脾脏长度、血清肌酐、尿素氮、尿蛋白、抗ds-DNA抗体、IgG水平均明显增加,肾脏出现狼疮样改变.但是,与姥鲛烷诱导的野生型B6小鼠相比,姥鲛烷诱导的S100A9-/-B6小鼠的狼疮样症状及以上血清学和尿液指标改变均明显减轻.结论:姥鲛烷可以使野生型B6小鼠和S100A9-/-B6小鼠出现狼疮病变,但S100A9基因敲除小鼠病变程度较轻,提示该基因对狼疮小鼠的发病可能有促进作用.

Objective:To explore the effects of S100A9 knockout on mice with lupus nephritis(LN)induced by pristane,and clarify specific roles of S100A9 in LN.Methods:Ten female wild-type(WT)C57BL/6(B6)mice and ten S100A9-/-B6 mice(6-8 weeks old)were used.Five WT B6 mice and five S100A9-/-B6 mice were intraperitoneally injected with 0.5 mL pristane,respectively,serving as experimental groups.Other five WT B6 mice and five S100A9-/-B6 mice were intraperitoneally injected with 0.5 mL normal saline,respectively,serving as control groups.The mice were sacrificed at six months after injection.The expression of anti-double-stranded DNA(ds-DNA)antibody was measured by ELISA.The levels of serum creatinine,serum urea nitrogen and urine protein were detected.Renal tissues were collected for HE staining to evaluate renal pathology.Results:There were no significant differences between WT and S100A9-/-B6 mice on mouse body-weight,spleen weight,kidney-structure,and serum creatitine levels etc.Compared with control B6 mice,pristane treated B6 mice showed increased weight and length of spleen as well as increased levels of serum creatinine,urea nitrogen,proteinuria,anti-ds-DNA antibody and IgG,and the lupus-like changes in the kidney with increased glomerular volume,edema or renal tuble epithelium,and stenosis of lumen.Similar results were observed in pristane-treated S100A9-/-B6 mice,compared with control S100A9-/-B6 mice.However,compared with pristane-treated WT B6 mice,the above symptoms of LN and indexes of serum and urine were mild in pristane-treated S100A9-/-B6 mice.Conclusion:Pristane induces systemic lupus erythematosus in B6 mice and S100A9-/-B6 mice.However,the degree of lesions in mice with S100A9 gene knockout is reduced,suggesting that this gene may have a promoting effect on the pathogenesis of lupus in mice.

查洁;杨小四;李帆;李晓静;姚根宏

安庆医药高等专科学校基础医学院,安徽 安庆 246052||南京医科大学鼓楼临床医学院风湿免疫科,江苏 南京 210008安庆医药高等专科学校基础医学院,安徽 安庆 246052南京医科大学鼓楼临床医学院风湿免疫科,江苏 南京 210008

临床医学

系统性红斑狼疮S100A9基因姥鲛烷

systemic lupus erythematosusS100A9 genepristane

《南京医科大学学报(自然科学版)》 2024 (004)

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国家自然科学基金(81970062,81901672);安徽省高校学科(专业)拔尖人才学术资助项目(gxbjZD2022105);安徽省高校自然科学研究项目(2023AH053426)

10.7655/NYDXBNSN230783

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