二苯乙烯苷对动脉硬化大鼠主动脉一氧化氮合酶表达及舒张作用的影响

Effects of 2,3,4',5-tetrahydroxystilbene-2-O-β-D glucoside on expression of nitric oxide synthase and endothelium dependent vasodilation in artery vessels of experimental atherosclerotic rats

目的探讨二苯乙烯苷(TSG)对动脉粥样硬化大鼠主动脉一氧化氮合酶(NOS)表达的影响及对主动脉的舒张作用。方法SD大鼠65只,(?),随机分为6组:正常对照组、模型组、辛伐他汀组、TSG 120 mg·kg^(-1)·d^(-1)组、TSG 60 mg·kg^(-1)·d^(-1)组及TSG 30 mg·kg^(-1)·d^(-1)组。采用高脂饲料喂饲+VitD_3复制大鼠动脉粥样硬化模型,造模12 wk后抽样检测大鼠主动脉,以大鼠动脉粥样硬化斑块形成为造模指标。经治疗6 wk后,分离主动脉,-70℃保存,Western blot检测主动脉组织中NOS含量,RT-PCR检测大鼠主动脉内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)mRNA表达,同时观察TSG对大鼠离体主动脉血管环内皮依赖性血管舒张作用的影响。结果与模型组相比,辛伐他汀组和TSG各剂量组均能显著增加主动脉组织eNOS表达及降低主动脉组织iNOS表达,并呈剂量依赖性。TSG抑制去甲肾上腺素(NA)诱发的内皮依赖性血管收缩、增强乙酰胆碱(Ach)内皮依赖性血管舒张;TSG的血管舒张作用可被NO前体物L-精氨酸增强,而NOS抑制药L-硝基精氨酸甲酯可部分削弱之。结论TSG能上调其主动脉eNOS和下调iNOS表达,并能使内皮依赖性血管舒张,这可能与TSG抗AS作用的机制有关。

AIM To investigate the effects of 2, 3, 4＇ , 5-tetrahydroxystilbene-2-O-β-D glucoside （TSG） on the expression of endothelium nitric oxide synthase （NOS） and endothelium dependent vasodilation in artery vessels of experimental atherosclerotic rats. METHODS The atherosclerosis model of rat was induced by high-fat diet and injected with VitD3. Sixty-five male rats were randomized into six groups： control group, model group, simvastatin group, TSG A group （TSG 120 mg·kg^-1·d^-1）, TSG B group （TSG 60mg·kg^-1·d^-1）, TSG C group （TSG 30 mg·kg^-1·d^-1） . Atherosclerotic plaque in aorta was observed to verify the model by randomsampling after 12 weeks. Six weeks after treatment, the aorta samples were separated from the bodies and placed at -70 ℃. Then western blotting method was adopted to detect the expressions of eNOS and iNOS, and half- quantitative reverse transcription polymerase chain reaction （RT-PCR） was used to measure the expressions of eNOS mRNA and iNOS mRNA in artery vessels. The effect of endothelium-dependent vasodilation of TSG was observed simultaneously. STATA8.0 software was used to analyze the differences among the groups. RESULTS Compared with model group, the expression of eNOS decreased significantly and the expression of iNOS increased remarkably in simvastatin group and three TSG group, and showed a dose-dependent effect. TSG inhibited endothelium dependent vasoconstriction induced by NA and enhanced the effect of endothelium dependent vasodilation. CONCLUSION TSG could upregulate the expression of eNOS, downregulate the expression of iNOS in aorta vessels of experimental atherosclerotic rats, and improve endothelium dependent vasodilation, which may be one of the anti-atherosclerosis mechanisms of TSG.