厄贝沙坦抑制高浓度葡萄糖诱导的脂质氧化效应和人脐静脉血管内皮细胞损伤

Irbesartan inhibits high glucose-induced lipid oxidation effect and human umbilical vein endothelial cell injury

目的探讨厄贝沙坦对高浓度葡萄糖诱导的脂质氧化效应及人脐静脉血管内皮细胞(HUVEC)损伤的影响。方法取生长良好的HUVEC进行实验。将细胞分为4组:正常浓度葡萄糖对照组(葡萄糖终浓度为5.5mmol/L)、高糖组(葡萄糖终浓度为33.3mmol/L)、厄贝沙坦干预组和抗氧化剂N-乙酰半胱氨酸(N-acetyl-cysteine,NAC)干预组。干预组首先用厄贝沙坦(10-5mol/L)和NAC(10mmol/L)分别预作用1h,而后加入33.3mmol/L葡萄糖共同孵育24、48、72h。分别采用TBARS法和分光光度比色法检测培养上清液中丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果与正常浓度葡萄糖组比较,高糖组MDA含量显著升高(P<0.01),SOD活性明显降低(P<0.01);高糖作用24h时MDA含量已达到较高水平(P<0.01),且随葡萄糖作用时间的延长(48、72h)MDA含量呈上升趋势,但与高糖作用24h比较,差异无统计学意义(P>0.05)。与高糖组比较,厄贝沙坦组和NAC组MDA含量均显著下降(P<0.05),SOD活性则均明显升高(P<0.05)。与高糖组比较,厄贝沙坦组和NAC组各时点细胞凋亡率均显著降低(P<0.05),高糖对HUVEC细胞形态的损伤明显减轻。结论厄贝沙坦部分通过抑制氧化应激作用降低高浓度葡萄糖诱导的脂质氧化效应,保护HUVEC。

Objective To discuss the influences of irbesartan on high glucose-induced lipid oxidation effect and human umbilical vein endothelial cell （HUVEC） injury. Methods HUVECs of the logarithmic phase were divided into four groups：normal-concentration glucose control group （glucose final concentration of 5.5 mmol/L）,high-glucose group （glucose final concentration of 33.3 mmol/L）,irbesartan intervention group,and anti-oxidant N-acetyl-cysteinyl acid （NAC） intervention group. The intervention groups were first treated with irbesartan （10-5mmol/L） and NAC （10 mmol/L） for 1 h,respectively,then co-incubated with high glucose （glucose final concentration of 33.3 mmol/L） for 24 h,48 h and 72 h. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity of culture supernatant were determined by TBARS method and spectrophotometric assay,respectively. Results MDA content increased significantly （P0.01） and SOD activity decreased significantly （P0.01） in high glucose group compared with control group. MDA content reached a considerable level （P0.05） when HUVECs were treated with high glucose for 24 hours; with time prolonging for 48 hours and 72 hours,the level of MDA had a slightly upward trend,but with no statistical significance （P0.05）. Compared with that in high glucose group,MDA content significantly decreased （P0.05） and SOD activity significantly increased （P0.05） in irbesartan-and NAC-treated groups. Apoptosis of HUVECs was significantly reduced （both P0.05） at each time point in irbesartan-and NAC-treated groups,and the damage of high glucose on morphology of HUVECs also reduced significantly. Conclusion Irbesartan reduces lipid oxidation induced by high glucose partially by inhibiting oxidative stress and thus protects HUVEC.