Page 31 - 南京医科大学自然版

第44卷第4期 南京医科大学学报（自然科学版）
2024年4月 Journal of Nanjing Medical University（Natural Sciences） ·469 ·

·基础研究·

S100A9基因敲除对姥鲛烷诱导小鼠狼疮肾炎的影响

查 洁 ，杨小四 ，李 帆 ，李晓静 ，姚根宏 2*
1，2
2
1
1
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
1 2
［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
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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
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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
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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
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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
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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
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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
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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
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轻，提示该基因对狼疮小鼠的发病可能有促进作用。
［关键词］ 系统性红斑狼疮；S100A9基因；姥鲛烷
［中图分类号］ R593.24 ［文献标志码］ A ［文章编号］ 1007⁃4368（2024）04⁃469⁃06
doi：10.7655/NYDXBNSN230783

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

1，2 1 1 2 2*
ZHA Jie ，YANG Xiaosi ，LI Fan ，LI Xiaojing ，YAO Genhong
Basic Medical School，Anqing Medical College，Anqing 246052；Department of Rheumatology and Immunology，
1 2
Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University，Nanjing 210008，China

［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）
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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
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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，
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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
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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

［基金项目］ 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）
∗
通信作者（Corresponding author），E⁃mail：yaogenhong@nju.edu.cn