在实验性中风中SGLT-2抑制剂和GLP-1受体激动剂对神经元和质细胞损伤的影响
Anna Murasheva1, Oksana Fuks1, Natalya Timkina1
1Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia.
Biomedicines
|January 8, 2025
概括
在中风模型中,-葡萄糖共运输体-2 (SGLT-2) 抑制剂和葡萄糖类-1 (GLP-1) 受体激动剂显示神经保护作用. GLP-1受体激动剂可以通过改善神经状态和减少非糖尿病大鼠的大脑损伤来提供更大的益处.
科学领域:
- 药理学和神经科学 药理学和神经科学
- 心血管和代谢疾病 心血管和代谢疾病
- 神经科学和中风研究
背景情况:
- -葡萄糖共运输体-2 (SGLT-2) 抑制剂和类似葡萄糖-1 (GLP-1) 受体激活剂已知具有心脏保护和脏保护作用.
- 它们的神经保护潜力,特别是在减轻中风严重程度和潜在机制方面,需要进一步阐明.
- 这项研究研究了不同选择性的SGLT-2抑制剂和GLP-1受体激动剂对非糖尿病和糖尿病动物模型中的脑损伤和神经功能的影响.
研究的目的:
- 评估SGLT-2抑制剂 (empagliflozin,canagliflozin) 和GLP-1受体激动剂 (dulaglutide) 对大脑损伤量和神经状态的神经保护作用.
- 在非糖尿病和2型糖尿病大鼠中风模型中比较这些药物的疗效与甲福明和安慰剂.
- 探索由这些治疗干预影响的机械路径,包括神经元和质损伤标志物.
主要方法:
- 在非糖尿病和2型糖尿病的Wistar大鼠中诱导了中风 (每组n=10).
- 治疗组在中风诱导前7天 (非糖尿病) 或8周 (糖尿病) 接受了empagliflozin,canagliflozin,dulaglutide或metformin.
- 在中风后评估了神经缺陷,大脑损伤量以及神经元 (神经纤维光链,神经元特异性化) 和质 (S100B) 损伤的标志物.
主要成果:
- 在非糖尿病大鼠中,所有测试药物都表现出抑制心脏病发作的效果,杜拉格卢提德和SGLT-2抑制剂的效果优于甲福林.
- 与甲福明和SGLT-2抑制剂相比,杜拉格胺显著改善了神经状态;所有药物都减少了神经元损伤标志物 (NLCs).
- 在糖尿病大鼠中,所有药物都减少了心脏病发作的大小和神经系统缺陷. 杜拉古和empagliflozin,但不是canagliflozin,也减少了质损伤标志物S100B.
结论:
- 在实验性中风模型中,SGLT-2抑制剂和GLP-1受体激活剂具有显著的神经保护性.
- GLP-1受体激动剂,如杜拉格卢提德,可能通过影响大脑损伤量和神经状态,特别是在非糖尿病条件下,提供更高的疗效.
- 虽然所有药物都能减少神经元损伤,但GLP-1受体激动剂和高度选择性的SGLT-2抑制剂 (empagliflozin) 在糖尿病中风模型中对神经质标记物产生更大的影响.
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