非诺贝特对糖尿病血管保护机制研究  

Study on the Vascular Protection Mechanism of Fenofibrate in Diabetes

作　　者：张冲 崔建 ZHANG Chong;CUI Jian(The Sixth People's Hospital of Zibo City,Zibo 255000,China;Zibo Maternal and Child Health Hospital,Zibo 255000,China)

机构地区：[1]淄博市第六人民医院,山东淄博255000 [2]淄博市妇幼保健院,山东淄博255000

出　　处：《药物生物技术》2024年第6期657-663,共7页Pharmaceutical Biotechnology

摘　　要：通过对糖尿病小鼠和体外高糖诱导小鼠主动脉内皮细胞进行研究,初步探讨非诺贝特对糖尿病血管功能的保护机制。通过四通道血管张力测定系统,检测非诺贝特对糖尿病小鼠主动脉血管收缩和舒张功能的影响;通过检测试剂盒分别检测糖尿病小鼠主动脉中血管舒张调节物质一氧化氮(NO)、血管收缩调节物质血栓素A2、以及过氧化氢酶和超氧化物歧化酶等氧化应激调节物的表达情况;通过体外小鼠主动脉内皮细胞(MAECs)造模实验,免疫印迹法分别测定血管舒张因子PPARα、p-AMPK、p-eNOS和收缩因子NF-κB、COX-2的表达情况。结果显示:1.高血糖能够影响小鼠主动脉血管功能,非诺贝特治疗后糖尿病主动脉对去甲肾上腺素和乙酰胆碱依赖性调节降低,改善了其收缩和舒张功能;2.非诺贝特可以上调主动脉NO的表达,来改善糖尿病小鼠血管的舒张功能;3.非诺贝特可以升高超氧化物歧化酶和过氧化氢酶的表达量,明显抑制高血糖引起的主动脉氧化应激反应;4.非诺贝特可以显著降低糖尿病小鼠血管收缩剂血栓素A2的表达含量,调节血管收缩功能;5.非诺贝特通过提高血管舒张因子p-eNOS、PPARα和AMPK的表达,降低缩血管因子NF-κB和COX-2的表达,协同调节血管内皮细胞功能。结论:非诺贝特通过PPARα/AMPK/eNOS途径增加一氧化氮合酶的表达,促使NO的产生,并能抑制氧化应激功能,调节糖尿病血管舒张功能;通过抑制NF-κB/COX-2途径的表达,减少缩血管物质TxA2等的产生,调节糖尿病血管收缩功能;这两种途径协同调节血管张力,保护糖尿病对血管的损伤。To investigate the protective mechanism of fenofibrate on the vascular function of diabetic mice and the aorta endothelial cells induced by high glucose in vitro,the effect of fenofibrate on the vasoconstriction and diastole of aorta in diabetic mice was detected by four-channel vascular tension measurement system.The expression of NO,Thromboxane A2,catalase and superoxide dismutase oxidative stress regulators in aorta of diabetic mice were detected by testing kit.The expressions of PPARα,p-AMPK,p-eNOS and NF-kB and COX-2 were detected by western blotting in mouse aortic endothelial cells(MAECs).The results showed:1.Hyperglycemia can affect the vascular function of aorta in mice,after fenofibrate treatment,the dependent regulation of norepinephrine and acetylcholine in diabetic aorta decreased,and the systolic and diastolic functions were improved;2.Fenofibrate can up-regulate the expression of NO in the aorta to improve the diastolic function of blood vessels in diabetic mice;3.Fenofibrate can increase the expression levels of oxide dismutase and catalase,and significantly inhibit the oxidative stress reaction of aorta caused by hyperglycemia;4.Fenofibrate can significantly reduce the expression of thromboxane A2 in diabetic mice and regulate the function of vasoconstriction;5.Fenofibrate can enhance the expression of vasodilator p-eNOS,PPARαand AMPK,and decrease the expression of vasodilator NF-kB and COX-2,thus synergically regulating the function of vascular endothelial cells.Fenofibrate can increase the expression of nitric oxide synthase through PPARa/AMPK/eNOS pathway,promote the production of NO,inhibit the oxidative stress function,and regulate the vasodilation function of diabetes mellitus.By inhibiting the expression of NF-B/COX-2 pathway,the production of TxA2 and other vasoconstricting substances can be reduced to regulate the vasoconstriction function of diabetes mellitus.These two pathways work together to regulate vascular tone and protect blood vessel damage caused by diabetes.

关 键 词：非诺贝特 血管张力 氧化应激 小鼠主动脉内皮细胞 血管因子 

分 类 号：R965[医药卫生—药理学]