摘要
目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂对AngⅡ刺激血管内皮细胞分泌血管活性因子的影响,并与AngⅡⅠ型受体(AT1R)拮抗剂losartan相对照,即从细胞水平进一步揭示PPARγ与高血压病的关系。方法以脐静脉内皮细胞为研究对象,观察PPARγ激动troglitazone对内皮细胞分泌内皮素-1(ET-1)和NO的影响,及其对AngⅡ刺激内皮细胞分泌ET-1和NO的影响,并与losartan相对照。结果10μmol/L和50μmol/Ltroglitazone使人脐静脉内皮细胞分泌ET-1含量与对照组相比虽有下降但无统计学意义,而NO与对照组相比明显升高(P<0.05);50μmol/Ltroglitazone可明显抑制AngⅡ(1×10-6mol/L)刺激的ET的分泌(P<0.05);两种浓度troglitazone均能抑制AngⅡ对内皮细胞生成NO的减低作用(P<0.05);losartan抑制AngⅡ刺激内皮细胞合成和分泌ET-1增加和抑制AngⅡ减弱内皮细胞合成和分泌NO的作用比troglitazone更为明显(P<0.05)。结论PPARγ激动剂troglitazone可抑制AngⅡ刺激内皮细胞合成和分泌ET-1的增加和NO的减少,但其作用并没有losartan明显,提示troglitazone通过影响血管活性因子的分泌而调节血压的作用并非完全是通过AT1R途径。
Objective To investigate the effects of peroxisome proliferator-activated receptor-γ （PPAR-γ） ligand on angiotensin Ⅱ （Ang Ⅱ ）-induced endothelin-1 （ET-1） and NO secretion by endothelial cells in comparison with Ang Ⅱ type Ⅰ receptor （AT1R） antagonist losartan, so as to reveal the relationship between PPAR γ and essential hypertension. Methods Cultured human umbilical vein endothelial cells （HUVECs） were treated with Ang Ⅱ, PPAR γ ligand troglitazone, Ang Ⅱ plus troglitazone, and Ang Ⅱ plus AT1R antagonist losartan, respectively, and the concentrations of NO and ET-1 in the cell culture supematant were measured to evaluate the effects of troglitazone and losartan on Ang Ⅱ -induced NO and ET-1 production by human endothelial cells. Results Treatment of the HUVECs with troglitazone at 10 μmol/L and 50 μmol/L did not produce significant changes in ET-1 concentration in the cell culture supematants, but significantly increased NO concentration as compared with the control group （P〈0.05）. Triglitazone at the concentration of 50 μmol/L significantly inhibited Ang Ⅱ （1×10^6 mol/L）-induced ET-1 production （P〈0.05）, and at both 10 and 50 μmol/L, troglitazone inhibited the NO release-lowering effect or Ang Ⅱ in the endothelial cells （P〈0.05）. Both troglitazone and losartan inhibited Ang Ⅱ -induced ET-1 production by the endothelial cells, but losartan showed more potent effect （P〈0.05）. Similarly, both troglitazone and losartan inhibited decreased NO production in response to Ang Ⅱ treatment, and again losartan showed stronger effect （P〈 0.05）. Conclusion PPAR γ ligand troglitazone can inhibit Ang Ⅱ -induced ET- 1 production enhancement and decreased NO release by the endothelial cells, but its effect is not so strong as losartan, suggesting that troglitazone modulates blood pressure not solely through AT1R pathway.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2007年第7期1030-1033,共4页
Journal of Southern Medical University
基金
陕西省科技攻关项目基金资助(2004K14-G1)~~
