单剂量二甲双胍改善急性糖负荷对高血压患者血管内皮功能的损伤

Single Dose of Metformin Reduces the Endothelial Damages Induced by Acute Glucose Loading in Essential Hypertensive Patients

目的探讨单剂量二甲双胍(MF)对原发性高血压患者在急性糖负荷后的内皮依赖性血管舒张功能、血清抗氧化物质及游离脂肪酸的影响。方法入选未经降压治疗的原发性高血压(EH)患者39例,随机分为高血压对照组(EH 组,未服用降压药,n=26)和二甲双胍组(MF 组,服用单剂量 MF,0.5 g/d,n=13);另选择同期健康体检者设为正常对照组(n=15)。入选者禁食12 h 后,口服葡萄糖耐量试验(OGTT)。以高分辨率血管彩超测定糖负荷0、1、2、3 h 后肱动脉血流介导的内皮依赖性血管舒张功能(FMD)。检测血清中超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)、抗超氧阴离子自由基(AntiO_2^-)和游离脂肪酸(FFA)的水平。结果急性糖负荷1 h 后,EH 组和正常对照组的 FMD 显著下降[EH 组(9.5±3.3)%比负荷前(13.6±5.0)%,P<0.05;正常对照组(14.4±5.9)%比负荷前(17.4±5.7)%,P<0.05],MF 抑制糖负荷对 FMD 的影响[MF 组1 h:(14.5±6.2)%比负荷前:(14.5±6.0)%,P>0.05]。急性糖负荷后1 h,EH 组的 SOD、T-AOC 及 AntiO_2^-浓度较空腹时显著下降,MF 抑制了急性糖负荷引起的 SOD 和 T-AOC 水平下降(P<0.05),Anti O_2^-水平甚至比负荷前明显升高[(256.8±72.2)U/L 比负荷前(224.8±67.8)U/L,P<0.05],且 FFA 浓度比糖负荷前明显下降[(108.1±53.1)μmol/L 比负荷前(236.6±80.5)μmol/L,P<0.05]。结论单一剂量的 MF 能改善急性糖负荷对高血压患者血管内皮功能的一过性损害,该作用可能与恢复抗氧化能力、降低游离脂肪酸水平有关。

Objective To study the protective effect of single dose of metformin on the time-response changes of flow mediated dilatation（FMD）, and serum antioxidants as well as free fatty acid levels after acute glucose loading in hypertensive patients. Methods Thirty-nine untreated hypertensive patients randomly to receive a single dose of metformin （MF, 0.5 g, n= 13） or placebo（EH, n= 26） with 15 healthy subjects as normal controls （NS, n= 15）. All subjects underwent oral glucose tolerance test （OGTT） after fasting for 12 hours. Brachial artery FMD, serum levels of superoxide dismutase （SOD）, total antioxidative capacity （T-AOC）, superoxide anion （Anti O2^- ）, and free fatty acid were determined before and after acute glucose loaded. Results Acute glucose loading impaired FMD in both EH and NS groups（EH： 1 h：9.5% ± 3.3 % vs 0 h： 13.6% ± 5.0 %, P〈0. 05; NS： 1 h： 14. 4%±5.9% vs 0 h：17. 4%^±5.7%, P〈0. 05）. Metformin prevented the decreases of FMD induced by acute glucose loading （MF： 1 h：14.5%±6.2% vs 0 h： 14.5%±6.0%, P〉0.05）. After acute glucose loading for 1 hour, serum levels of SOD, T-AOC, Anti O2^- were significantly decreased in the EH group. However, Metformin inhibited the decreases in Anti O2^- （256.8 ±72.2 U/L vs 0 h：224.8±67.8 U/L, P〈0.05）, and decline of serum SOD, T-AOC change after acute glucose loading（P〉0.05） with concomitantly decreases in free fatty acid （108. 1±53.1 umol/L vs 0 h： 236.6±80.5 umol/L, P〈0.05）. Conclusion Single dose metformin prevents impairment of endothelial function induced by acute glucose load in hypertensive patients, which is associated with the improvement of antioxidant ability and the reduced free fatty acid levels.