目的：探讨过氧化物酶体增殖物受体γ（ PPARγ）对高糖介导的血管内皮细胞活性氧（ ROS）生成的影响及机制。方法：人脐静脉内皮细胞（ HUVECs ）以高糖（33 mmol／L D-葡萄糖）培养基培养，并以低糖培养基（5.5 mmol／L D-葡萄糖）作为对照。分别利用超氧阴离子和一氧化氮（ NO）的荧光探针观察PPARγ激动剂比格列酮对高糖环境下内皮细胞超氧阴离子和NO水平的影响，以Western blotting 法观察解偶联蛋白2（ UCP2）的表达。结果：PPARγ激动剂比格列酮可显著抑制高糖介导的ROS生成，并可防止高糖介导的内皮细胞NO水平的下降，而上述作用可被PPARγ的阻断剂GW9662所阻断。 PPARγ激动剂可上调内皮细胞UCP2的表达，而通过genipin抑制UCP2可显著减弱PPARγ激动剂的作用。结论：激活PPARγ可显著抑制高糖介导的ROS的生成，而该作用可能与其上调UCP2的表达有关。%AIM:To explore the effects of PPARγon the elevated level of reactive oxygen species ( ROS) in-duced by high glucose and its mechanism .METHODS:Human umbilical vein endothelial cells ( HUVECs) were cultured with DMEM containing high glucose (33 mmol/L D-glucose), and DMEM containing lower glucose (5.5 mmol/L D-glu-cose) was used as control .Superoxide anion and nitric oxide fluorescence probes were used to observe the effects of PPAR γagonist on ROS and NO productions in the HUVECs .The uncoupling protein 2 (UCP2) protein level in the HUVECs was detected by Western blotting .RESULTS:PPARγagonist pioglitazone inhibited the ROS generation and prevented the de-crease in NO level under high glucose condition , and these effects were reversed by pretreatment with PPARγantagonist GW9662.The results of Western blotting indicated that PPARγagonist pioglitazone up-regulated the UCP2 expression un-der high glucose condition , and this effect was also blocked by GW 9662.Inhibition of UCP2 by genipin attenuated the effect of pioglotazone on the ROS production .CONCLUSION: Activation of PPARγinhibits ROS generation under high glucose condition , and this effect may mediate by up-regulation of UCP2.
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