天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (8): 812-817.doi: 10.11958/20203525

• 实验研究 • 上一篇    下一篇

LTBP2通过TLR4/NF-κB信号通路抑制糖尿病大鼠海马神经元凋亡

栾宁 1，刘丹 1，刘畅 1，王新杨 1，侯阳 2，张晓妍 1△   

  1. 1锦州医科大学附属第一医院老年医学科（邮编121001）；2锦州医科大学生命科学院
  • 收稿日期:2020-12-21 修回日期:2021-03-16 出版日期:2021-08-15 发布日期:2021-08-19
  • 通讯作者: 张晓妍 E-mail:fs.zxy@163.com
  • 作者简介:栾宁（1982），女，硕士，主管护师，主要从事老年病慢性病的治疗方面研究。E-mail：9771880@qq.com
  • 基金资助:
    辽宁省自然科学基金指导计划（20180550197）

LTBP2 inhibits apoptosis of hippocampal neurons through TLR4/NF-κB signaling pathway in diabetic rats

LUAN Ning1, LIU Dan1, LIU Chang1, WANG Xin-yang1, HOU Yang2, ZHANG Xiao-yan1△   

  1. 1 Department of Geriatrics, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China; 2 Academy of Life Sciences, Jinzhou Medical University △Corresponding Author E-mail: fs.zxy@163.com
  • Received:2020-12-21 Revised:2021-03-16 Published:2021-08-15 Online:2021-08-19

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摘要： 目的 探讨沉默潜在转化生长因子 β 结合蛋白 2（LTBP2）基因对糖尿病大鼠学习记忆功能的影响及 机制。方法 雄性SD大鼠45只一次性腹腔注射链脲佐菌素（STZ）55 mg/kg，72 h后采尾静脉血测血糖，将血糖＞ 16.7 mmol/L 的大鼠定为糖尿病模型；模型诱导成功后将大鼠随机分成3组：糖尿病（DM）组、si-LTBP2组（大鼠海马 给予腺病毒包装的针对LTBP2的siRNA 10 μL）、sc-LTBP2组（大鼠海马给予LTBP2对照序列10 μL），每组15只。另 取15只正常大鼠作为对照（CON）组。12周后，水迷宫检测大鼠学习记忆能力；免疫组织化学染色和实时荧光定量聚 合酶链式反应（qPCR）检测海马LTBP2表达；Western blot检测海马LTBP2、Toll样受体4（TLR4）、核因子（NF）-κB蛋 白相对表达量；TUNEL染色检测海马神经元凋亡。结果 与CON组相比，DM组、si-LTBP2组和sc-LTBP2组LTBP2、 TLR4、NF-κB表达明显增加，海马神经元凋亡明显增多，大鼠学习记忆能力明显下降（均P＜0.05）。与DM组相比， si-LTBP2 组 LTBP2、TLR4、NF-κB 表达明显降低，海马神经元凋亡明显减少，大鼠学习记忆能力明显提升（均 P＜ 0.05）。结论 沉默海马LTBP2的表达可明显改善糖尿病大鼠学习记忆能力，其机制可能与抑制TLR4/NF-κB信号 通路有关。

关键词: 糖尿病, 1型, Toll样受体4, NF-κB, 细胞凋亡, 学习, 记忆, 潜在转化生长因子β结合蛋白2, TLR4/NF-κB 信号通路

Abstract: Objective To investigate the effect and mechanism of silencing latent transforming growth factor beta binding protein 2 (LTBP2) gene on learning and memory function of diabetic rats. Methods Forty-five male SD rats were given a single intraperitoneal injection of streptozotocin (STZ) at 55 mg/kg, and blood glucose was collected from the tail vein at 72 hours. Rats with a blood glucose concentration greater than 16.7 mmol/L were designated as diabetes model rats. After the model was successfully induced, the rats were randomly divided into 3 groups: diabetes group (DM), si-LTBP2 group (the hippocampus of rats was given 10 μL adenovirus packaged siRNA targeting LTBP2) and sc-LTBP2 group (the rats were given LTBP2 control sequence 10 μL in hippocampus). Another 15 normal rats were used as control group (CON group). After 12 weeks, the learning and memory ability were detected by water maze, the expression of hippocampal LTBP2 was detected by immunohistochemical staining and the relative expressions of hippocampal LTBP2, Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) protein were detected by Western blot assay. The apoptosis of hippocampal neurons was detected by TUNEL staining. Results Compared with the CON group, the expressions of LTBP2, TLR4 and NF-κB were significantly increased in the DM group and the sc-LTBP2 group. The apoptosis of hippocampal neurons was significantly increased, and the learning and memory ability of rats was significantly decreased (all P＜0.05). Compared with the DM group, the expression levels of LTBP2, TLR4 and NF-κB were significantly reduced, the apoptosis of hippocampal neurons was significantly reduced, and the learning and memory ability of rats was significantly improved in the si-LTBP2 group (all P＜0.05). Conclusion Silencing the expression of LTBP2 in the hippocampus can significantly improve the learning and memory ability of diabetic rats, and its mechanism may be related to the inhibition of the TLR4/NF-κB signaling pathway.

Key words: diabetes mellitus, type 1, Toll-like receptor 4, NF-kappa B, apoptosis, learning, memor, latent transforming growth factor beta binding protein 2, TLR4/NF-kappa B signaling pathway

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