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目的:观察球状脂联素(gANT)对高脂血症大鼠血管内皮功能的影响,并探讨其主要信号转导机制。方法:选14只8周龄雄性SD大鼠分为对照组及高脂血症组(每组7只),分别以普通和高脂饲料喂养14周后,麻醉采血,用生化分析仪检测血清胆固醇和三酰甘油的水平,用ELISA法检测血浆脂联素(ANT)的水平。分离大鼠主动脉,与gANT共孵育,观察gANT对血管内皮功能、血管超氧化物生成量以及一氧化氮合酶(NOS)表达水平的影响。结果:与对照组比较,高脂血症组大鼠血浆胆固醇、三酰甘油及ANT的水平显著升高(P<0.01;P<0.05;P<0.05);血管内皮功能明显失调[乙酰胆碱引起的血管最大舒张率显著降低:(70.3±3.3)%vs.(95.2±2.5)%,P<0.01];血管组织中超氧化物生成显著增多(P<0.01);磷酸化内皮型NOS(p-eNOS)的表达降低(P<0.05),诱导型NOS(iNOS)的表达明显增加(P<0.01)。gANT可显著改善高脂血症组大鼠血管对ACh的舒张反应(P<0.01),降低超氧化物生成(P<0.01),上调p-eNOS表达(P<0.05)及抑制iNOS过表达(P<0.05)。结论:gANT可显著改善高脂血症组大鼠血管内皮功能,其机制与促进具有血管保护作用的一氧化氮(NO)的生成有关,也与其减少NO破坏有关。
Objective: To observe the effect of globular adiponectin (gANT) on vascular endothelial function in hyperlipidemic rats and to explore its main signal transduction mechanism. Methods: Fourteen 8-week-old male Sprague-Dawley rats were divided into control group and hyperlipidemia group (7 in each group). The rats were fed with normal and high-fat diet for 14 weeks respectively, then blood was collected by anesthesia and serum was detected by biochemical analyzer Cholesterol and triglyceride levels were measured by ELISA for plasma adiponectin (ANT) levels. The aorta of rats were isolated and incubated with gANT to observe the effect of gANT on vascular endothelial function, vascular superoxide production and nitric oxide synthase (NOS) expression. Results: Compared with the control group, the levels of plasma cholesterol, triglyceride and ANT in hyperlipemia group were significantly increased (P <0.01; P <0.05; P <0.05); the vascular endothelial dysfunction [acetylcholine-induced (70.3 ± 3.3)% vs (95.2 ± 2.5)%, P <0.01]. The production of superoxide in vascular tissue was significantly increased (P <0.01). The phosphorylation of endothelial nitric oxide synthase (p-eNOS) ) (P <0.05). The expression of iNOS increased significantly (P <0.01). gANT significantly reduced the vasorelaxation of ACh in rats with hyperlipidemia (P <0.01), decreased the production of superoxide (P <0.01), up-regulated the expression of p-eNOS and inhibited the expression of iNOS P <0.05). Conclusion: gANT can significantly improve the vascular endothelial function in rats with hyperlipidemia, which is related to the promotion of the production of nitric oxide (NO) with vascular protection and also to the reduction of NO destruction.