不同发育阶段 BTBR T+Itpr3tf 孤独症小鼠 T 细胞亚群异常研究
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昆明医科大学第二附属医院实验中心,昆明 650101

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R-33


Abnormal T cell subsets of BTBR T+Itpr3tf autistic mice at different developmental stages
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Experimental Center of the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China

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    摘要:

    目的 为了研究 4 周、8 周和 12 周龄 BTBR T+Itpr3tf孤独症小鼠脾 T 细胞亚群表达情况,明确用于研究免疫异常与孤独症关系的最适 BTBR 孤独症小鼠年龄。 方法 随机选取 5 ~ 6 只 4 周、8 周和 12 周龄雄性 BTBR 小鼠与对应年龄的同性别 C57BL / 6J 小鼠进行三箱社交实验、理毛实验和埋珠实验;取 8 周龄和12 周龄小鼠脾制成单细胞悬液,通过流式细胞技术检测 8 种 T 细胞亚群(TH 1、TH 2、TH 17、TC1、TC2、TC17、TFH和 Treg)细胞。 结果 4 周、8 周和 12 周龄 BTBR 小鼠相较于同龄 C57 小鼠,社交时间减少(P<0. 001),理毛时间增加(P<0. 01,P<0. 001),8 周龄和 12 周龄 BTBR 小鼠埋珠数量增多(P<0. 01,P<0. 001);与同龄 C57 小鼠相比,8 周龄 BTBR 小鼠 TH 1(P<0. 001)、TH 2(P<0. 01)、TC1(P<0. 05)、TC2(P<0. 001)、TFH(P<0. 01)细胞表达明显增加,Treg 细胞(P<0. 001)明显降低;12 周龄 BTBR 小鼠 TH 1(P<0. 01)、TH 2(P<0. 01)、TH 17(P<0. 05)、TC1(P<0. 01)、TC2(P<0. 001)、TC17(P<0. 01)、TFH(P<0. 001)细胞表达增加,Treg 细胞(P<0. 05)表达降低。不同年龄阶段,8 周龄 BTBR 小鼠较 12 周龄小鼠,TH 1 / Treg,TC1 / Treg 比例明显升高(P<0. 05),而 TC17 / Treg 比例降低。 结论 不同发育阶段 BTBR 小鼠均表现出不同程度的 Teff/ Treg 比例异常增高;结合行为学数据,建议使用 8 周龄 BTBR 小鼠用于开展孤独症与免疫异常的研究。

    Abstract:

    Objective To investigate the expression of T cell subsets in the spleen of BTBR T+Itpr3tf autistic mouse at 4, 8, and 12 weeks of age, and to determine the optimal age for studying the relationship between immune abnormalities and autism in BTBR autistic mice. Methods It randomly selected 5~6 male BTBR mouse at 4 weeks, 8 weeks, and 12 weeks of age and C57BL / 6J mouse of the same gender at corresponding ages for the three-box social interaction test, the self-grooming test, and the marble-burying test; Single cell suspensions were prepared from the spleens of mouse at 8 and 12 weeks of age, and flow cytometry was used to detect 8 subsets of T cells (TH 1, TH 2, TH 17, TC1, TC2, TC17, TFH , and Treg). Results Compared with C57BL / 6J mouse of the same age, BTBR mouse at 4 weeks, 8 weeks, and 12 weeks of age showed a decrease in social time(P<0. 001), an increase in grooming time (P<0. 01,P<0. 001), and an increase in the number of marbles buried(P<0. 01,P<0. 001) in BTBR mouse at 8 weeks and 12 weeks of age. As well, the expression of TH 1(P<0. 001), TH 2(P<0. 01), TC1(P<0. 05), TC2(P<0. 001), and TFH(P<0. 01)cells in 8-week-old BTBR mouse were significantly increased, while the expression of Treg (P<0. 001)cells were significantly decreased; The expression of TH 1(P<0. 01), TH 2(P<0. 01), TH 17(P<0. 05),TC1(P<0. 01), TC2(P<0. 001), TC17(P<0. 01), and TFH ( P<0. 001) increased in 12-week-old BTBR mouse,while the expression of Treg(P<0. 05) cells decreased. At different age stages (P<0. 050) the ratio of TH 1 / Treg and TC1 / Treg in 8-week-old BTBR mouse were significantly higher than those in 12 week old mouse, while the TC17 / Treg ratio decreased. Conclusions BTBR mouse at different developmental stages exhibit varying degrees of abnormal increase in Teff / Treg ratio. Based on result of behavioral test, it is recommended to use 8-week-old BTBR mice for research on autism and immune abnormalities.

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申 晨,李 萌,聂祖庆,李志伟,文 婕,杜娟娟,奎秀莹,杨菁瑞,曹 霞.不同发育阶段 BTBR T+Itpr3tf 孤独症小鼠 T 细胞亚群异常研究[J].中国比较医学杂志,2025,(3):30~39,47.

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  • 收稿日期:2024-08-16
  • 在线发布日期: 2025-05-29
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