Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Jiangsu, 210008, Nanjing, China.
Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 210008, Nanjing, Jiangsu, China.
Lipids Health Dis. 2021 Jan 12;20(1):5. doi: 10.1186/s12944-021-01430-y.
Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown.
ApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA.
Empagliflozin reduced the atherosclerotic lesion burden (-8.6 %, P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g, P = 0.002), lipid profiles (TC: [-15.3 mmol/L, P = 0.011]; TG: [-2.4 mmol/L, P < 0.001]; LDL: [-2.9 mmol/L, P = 0.010]), RAAS (renin [-9.3 ng/L, P = 0.047]; aldosterone [-16.7 ng/L, P < 0.001]) and sympathetic activity (norepinephrine [-8.9 ng/L, P = 0.019]; neuropeptide Y [-8.8 ng/L, P = 0.002]). However, the anti-inflammatory effect of empagliflozin was not significantly evident.
The early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.
几项大型临床试验证实了钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）在 2 型糖尿病患者中的心脏保护作用。然而，依帕列净作为 SGLT2i 是否能减轻非糖尿病状态下的动脉粥样硬化进展尚不清楚。
ApoE-/- 小鼠喂食西方饮食 12 周以诱导动脉粥样硬化。在第 7 周时，一组小鼠用含有依帕列净（10mg/kg/天）的饮用水处理，另一组给予普通水。在第 12 周时，采集每组的整个主动脉。进行油红 O、HE 和 Movat 染色，以测量动脉粥样硬化病变面积和大小。通过 ELISA 测量小鼠血清脂质谱（总胆固醇[TC]、甘油三酯[TG]、低密度脂蛋白-c[LDL]和高密度脂蛋白-c[HDL]）、全身炎症水平（IL-1β、IL-6 和 IL-10）、肾素-血管紧张素-醛固酮系统（RAAS）成分和交感神经活性（去甲肾上腺素和神经肽 Y）指标。
依帕列净降低了 ApoE-/- 小鼠主动脉根部的动脉粥样硬化病变负担（-8.6%，P=0.004）。此外，依帕列净降低了体重（-3.27g，P=0.002）、脂质谱（TC：[-15.3mmol/L，P=0.011]；TG：[-2.4mmol/L，P<0.001]；LDL：[-2.9mmol/L，P=0.010]）、RAAS（肾素[-9.3ng/L，P=0.047]；醛固酮[-16.7ng/L，P<0.001]）和交感神经活性（去甲肾上腺素[-8.9ng/L，P=0.019]；神经肽 Y[-8.8ng/L，P=0.002]）。然而，依帕列净的抗炎作用并不明显。
依帕列净治疗的小鼠早期动脉粥样硬化病变大小不太明显。依帕列净可降低动脉粥样硬化中的脂质谱和交感神经活性。
