NFATc1对糖尿病动脉粥样硬化ApoE-/-小鼠肠道菌群的影响

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摘要目的：探究活化T细胞核因子胞浆1型（nuclear factor of activated T-cells, cytoplasmic 1, NFATc1）对糖尿病动脉粥样硬化ApoE-/-小鼠肠道菌群的影响。方法：通过链脲佐菌素诱导ApoE-/-小鼠，构建糖尿病动脉粥样硬化小鼠模型，尾静脉注射腺相关病毒干扰体内NFATc1的表达。8周后处死小鼠，取其主动脉组织进行蛋白质印迹，验证NFATc1在主动脉中的敲减情况；通过HE染色分析主动脉粥样硬化斑块的相对面积。收集小鼠粪便，进行Illumina MiSeq测序，通过生物信息学分析小鼠肠道菌群纲水平的变化。结果：成功构建糖尿病动脉粥样硬化小鼠模型，尾静脉注射NFATc1敲减腺相关病毒后，其主动脉内NFATc1表达显著减少（P＜0.05）。HE染色显示主动脉有明显的粥样斑块形成，相较于阴性对照组，干扰NFATc1表达后斑块相对面积显著减小（P＜0.05）。16S rRNA基因测序结果显示，敲减NFATc1小鼠肠道内产芽胞菌纲的相对丰度（78.82%）较阴性对照组小鼠（32.93%）明显升高（W值=2）。结论：NFATc1可改变糖尿病动脉粥样硬化ApoE-/-小鼠肠道菌群的相对丰度。

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	刘嘉
	孙振
	侯丽娜
	钱勇江
	邵晨
	袁伟
	王中群

关键词 ：糖尿病, 动脉粥样硬化, 肠道菌群, NFATc1, 高通量测序

Abstract：Objective: To explore the effect of nuclear factor of activated Tcell cytoplasmic 1（NFATc1）on the intestinal microflora of diabetic atherosclerosis ApoE-/- mice. Methods: ApoE-/- mice were used to make diabetic atherosclerosis models by the injection of Streptozotocin. AdenoAssociated Viral Vector was injected into the tail vein to interfere with the expression of NFATc1 in vivo. The mice were sacrificed 8 weeks later, and aorta tissues were separated for Western blotting to verify efficacy of the knockdown of NFATc1 in the aorta. The relative area of atherosclerotic plaque was analyzed by HE staining. Mice feces were collected and nuclear acid were extracted for detecting gene sequence by Illumina MiSeq. Class levels of intestinal microflora of mice were determined through bioinformatics analysis. Results: The mouse models of diabetic atherosclerosis were successfully made. After the NFATc1 knockdown AdenoAssociated Viral Vector was injected into the tail vein, its expression was significantly reduced in the aorta（P＜0.05）.HE staining showed that the formation of atherosclerotic plaques in the aorta was significant, but the relative area of atherosclerotic plaques decreased significantly after interfering with the expression of NFATc1, compared to the negative control group（P<0.05）. The 16S rRNA gene sequencing results showed that the relative abundance of Erysipelotrichi in the intestine of NFATc1 knockdown mice was significantly higher than that of negative control mice（78.82% vs. 32.93%，W=2）. Conclusion: NFATc1 could change the relative abundance of intestinal microflora in diabetic atherosclerosis ApoE-/- mice.

收稿日期: 2021-03-16

基金资助:国家自然科学基金资助项目（82070455，81770450）；江苏省自然科学基金资助项目（BK20201225）；江苏大学实验动物中心大学生科技创新资助项目；江苏省研究生科研创新计划（KYCX20_2881）

通讯作者: 王中群（通讯作者），副研究员，博士生导师，E-mail：wangtsmc@126.com

作者简介: 刘嘉（1995—），女，硕士研究生

引用本文:

刘嘉，孙振，侯丽娜，钱勇江，邵晨，袁伟，王中群. NFATc1对糖尿病动脉粥样硬化ApoE-/-小鼠肠道菌群的影响[J]. 江苏大学学报:医学版, 2021, 31(04): 314-320. LIU Jia, SUN Zhen, HOU Lina, QIAN Yongjiang, SHAO Chen, YUAN Wei, WANG Zhongqun. Effects of NFATc1 on intestinal microflora of diabetic atherosclerosis ApoE-/- mice. Journal of Jiangsu University(Medicine Edition), 2021, 31(04): 314-320.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2021/V31/I04/314

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