S100A9基因敲除对姥鲛烷诱导小鼠狼疮肾炎的影响
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R593.24

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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)


Effects of S100A9 knockout on pristane⁃induced lupus nephritis in mice
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    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。

    Abstract:

    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.

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查洁,杨小四,李帆,李晓静,姚根宏. S100A9基因敲除对姥鲛烷诱导小鼠狼疮肾炎的影响[J].南京医科大学学报(自然科学版),2024,(4):469-474

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  • 收稿日期:2023-08-21
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  • 在线发布日期: 2024-04-11
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