莫卢金激活GLP-1R以改善2型糖尿病小鼠的认知功能障碍
Zhuanzhuan Wang1, Xin Cui1, Wenhui Yan2
1Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China; Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
Life sciences
|August 22, 2023
概括
来自传统中医药的小分子mollugin通过激活GLP-1R通路来改善2型糖尿病的认知功能障碍. 这种化合物增强神经元健康,减少氧化应激,提供一种潜在的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 糖尿病认知功能障碍是越来越令人担忧的越来越多的发病率.
- 葡萄糖类-1受体 (GLP-1R) 激动剂在改善糖尿病患者的认知缺陷方面表现有前途.
研究的目的:
- 研究来自传统中医 (TCM) 的小分子GLP-1R激动剂的潜力,以改善糖尿病认知功能障碍.
- 评估一种TCM衍生化合物素在改善与2型糖尿病 (T2DM) 相关的认知障碍方面的疗效.
主要方法:
- 使用细胞膜染色学 (CMC) 用GLP-1R-HEK293细胞膜柱对TCM小分子进行查.
- 使用MTT测定,流细胞计和免疫光检测,对暴露于高葡萄糖/过氧化 (HG/H2O2) 的PC12细胞的mollugin影响的评估.
- 通过实时PCR对小鼠大脑皮层的mRNA表达的分析和使用T2DM小鼠水迷宫测试评估认知功能.
主要成果:
- 莫卢金被证明与GLP-1R结合,促进的流入,增加β-TC-6细胞中的胰岛素分泌和cAMP水平.
- 在HG/H2O2诱导的损伤中,mollugin增强了PC12细胞活力,减少了亡,并降低了活性氧物种 (ROS) 水平.
- 在T2DM小鼠中,软蛋白缩短了逃逸延迟,改善了神经元损伤,并减少了Pik3ca,Akt1和Mapk1在大脑皮层中的mRNA表达.
结论:
- 莫卢金有效地改善了T2DM小鼠的认知功能障碍.
- 软菌素的治疗作用归因于GLP-1R/cAMP/PKA信号通路的激活.
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