GW0742对高糖损伤大鼠胸主动脉内皮的保护作用

发布时间：2018-03-31 23:24

本文选题：GW　切入点：高糖　出处：《中国药理学通报》2015年12期

【摘要】：目的探讨GW0742对高糖损伤大鼠胸主动脉内皮的作用及可能机制。方法葡萄糖55 mmol·L~(-1)(high glucose,HG)孵育大鼠胸主动脉,以乙酰胆碱(acetylcholine,ACh)诱导的内皮依赖性舒张作用为内皮功能完整性指标,HE染色观察血管形态结构变化,硝酸还原法测量血管内一氧化氮(nitric oxide,NO)含量,利用q RT-PCR和Western blot方法检测血管中过氧化物酶增殖物激活受体β(peroxisome proliferator-activated receptorβ,PPARβ)、核转录因子κB(nuclear transcription factor-κB,NF-κB)及内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)m RNA和蛋白表达。结果 HG条件下,ACh的内皮依赖性舒张作用明显减弱(P0.01),内皮功能受损;血管内皮细胞和平滑肌细胞结构完整性也被破坏;同时,PPARβm RNA和蛋白表达明显降低(P0.01),而NF-κB p65的表达则升高(P0.01),e NOS的表达下降(P0.01),血管内NO含量亦减少(P0.01);GW0742(0.01、0.1、1μmol·L~(~(-1)))能剂量依赖性地改善高糖损伤的ACh内皮依赖性舒张作用(P0.01),减轻内皮细胞和平滑肌细胞的损伤,上调PPARβ表达,减少NF-κB p65的表达,增加e NOS表达和NO的浓度(P0.01)。结论 GW0742对高糖损伤的大鼠胸主动脉内皮有保护作用,该作用可能与其激活PPARβ,下调NF-κB,改善e NOSNO系统有关。
[Abstract]:Objective to investigate the effect of GW0742 on the endothelium of thoracic aorta of rats with high glucose injury and its possible mechanism. Methods the thoracic aorta of rats was incubated with glucose 55 mmol L~(-1)(high glucose. The endothelium-dependent relaxation induced by acetylcholine acetylcholine acetylcholine (ache) was used as an index of endothelial functional integrity to observe the changes of vascular morphology and structure by HE staining, and the nitric oxide nitric oxide (no) content in blood vessels was measured by nitric acid reduction method. Q RT-PCR and Western blot were used to detect the expression of peroxisome proliferator-activated receptor 尾 PPAR 尾, nuclear transcription factor B(nuclear transcription factor- 魏 B, endothelial nitric oxide synthase NOS)m RNA and protein in blood vessels. The dependent diastolic effect was significantly decreased, and the endothelial function was impaired. The structural integrity of vascular endothelial cells and smooth muscle cells was also destroyed. At the same time, the expression of PPAR 尾 m RNA and protein decreased significantly, while the expression of NF- 魏 B p65 increased and the expression of P0.01e NOS decreased. The content of no in blood vessel also decreased P0.01GW0742C0.01 渭 mol L-1). It can improve the endothelium-dependent relaxation effect of ACh induced by high glucose injury in a dose-dependent manner and alleviate the endothelium-dependent relaxation effect of P0.01. Damage to cells and smooth muscle cells, The expression of PPAR 尾 was up-regulated, the expression of NF- 魏 B p65 was decreased, the expression of e NOS and the concentration of no were increased. Conclusion GW0742 has protective effect on thoracic aorta endothelium in rats with high glucose injury, which may be related to its activation of PPAR 尾, down-regulation of NF- 魏 B and improvement of e NOSNO system.
【作者单位】：重庆医科大学药理学教研室重庆市生物化学与分子药理学重点实验室;遵义医学院药理教研室基础药理省部共建教育部重点实验室;重庆科瑞制药(集团)有限公司;
【基金】：国家自然科学基金资助项目(NO 81100905)
【分类号】：R965

【相似文献】