在PPARγ激活剂中添加SGLT2共载体抑制剂并没有在治疗糖尿病引起的血管功能障碍方面产生添加效应
Aneta Cinakova1, Peter Krenek1, Jan Klimas1
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia.
Pharmacology
|October 16, 2023
概括
皮奥格利塔单一治疗改善了糖尿病大鼠的血管功能和减少了炎症,而达帕格利弗洛辛的效果较低. 组合疗法对血管活性或氧化应激没有增加的益处,但确实降低了IL6水平.
科学领域:
- 心血管药理学心血管药理学
- 内分泌学 在内分泌学.
- 糖尿病学 糖尿病学
背景情况:
- 内皮功能障碍 (ED) 是糖尿病血管并发症的核心原因.
- 达帕格利弗洛辛 (Dapa) 和皮奥利塔 (Pio) 均显示出糖尿病单独治疗的治疗潜力.
- 研究SGLT2抑制和PPAR-γ激活在1型糖尿病 (T1DM) 中对ED的联合抑制.
研究的目的:
- 评估PPAR-γ同时激活和SGLT2抑制对实验T1DM中的内皮功能障碍的疗效.
- 为了确定组合治疗是否比单一治疗更有效地使血管反应正常化.
主要方法:
- 实验T1DM诱导在Wistar大鼠使用链毒素 (STZ).
- 口服Dapa (10 mg/kg),Pio (12 mg/kg) 或它们的组合.
- 通过功能研究和实时qPCR进行大动脉评估,STZ后六周.
主要成果:
- 糖尿病老鼠的大动脉显示放松功能受损,血管活性因子 (eNos,Et1) 失衡,炎症和氧化应激标志物增加.
- 皮奥格利塔单独治疗使血管活性正常化并恢复Et1-eNos平衡;但达帕格利弗洛单独治疗无效.
- 这两种单一疗法都显著降低了炎症和氧化应激标志物. 组合疗法显示增加IL6减少.
结论:
- 皮奥格利塔单一治疗在实验T1DM中显示出显著的血管保护作用.
- 与达帕格利弗洛辛的联合疗法在血管活性或氧化应激方面没有产生添加效益.
- 联合治疗有效地影响了IL6的下调,这表明它具有特定的抗炎作用.
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