NLRP3抑制剂可缓解血糖变化诱发的2型糖尿病老年大鼠认知功能障碍

IF 3.8 3区 医学 Q2 CELL BIOLOGY
Wei Yang, Si-Cong Si, Jing Li, Yi-Xin Ma, Huan Zhao, Jia Liu
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引用次数: 0

摘要

血糖变异(GV)会明显加剧老年 2 型糖尿病(T2DM)患者的认知障碍,部分原因是慢性炎症。本研究调查了 NLRP3 炎性体抑制剂 MCC950 在老年 T2DM 大鼠模型中减轻 GV 引起的认知障碍的疗效。将诱导 T2DM 的老年 Sprague-Dawley 大鼠置于龙胆紫条件下,通过测量体重、血糖、血脂、胰岛素水平、炎症标志物和认知功能来评估 MCC950 的效果。对海马和前额叶皮层进行了转录组分析。与对照组相比,MCC950能明显减轻龙胆紫组的体重减轻和高血糖症状。MCC950还降低了胆固醇、甘油三酯和促炎标志物(白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18))的水平。最值得注意的是,MCC950能改善龙胆紫组的空间学习能力和记忆保持能力。免疫组化分析表明,炎性体激活减少,海马中神经元标志物 NeuN 的表达水平升高。转录组分析表明,MCC950改变了海马中神经活性配体与受体的相互作用途径,并影响了前额叶皮质中受体结合和细胞粘附过程。这些发现验证了 NLRP3 抑制剂在减轻 GV 诱导的 T2DM 老年大鼠认知功能损害方面的功效,并为后续临床研究提供了基础,以探索 NLRP3 靶向干预在解决糖尿病相关认知功能损害方面的更广泛潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
NLRP3 inhibitor alleviates glycemic variability-induced cognitive impairment in aged rats with type 2 diabetes mellitus
Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1β (IL-1β) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.
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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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