动态观察实验性高脂血症对血管内皮活性物质含量及其基因表达的影响以及DDPH的内皮细胞保护作用

Dynamic observation on the effect of various degree hyperlipidemia on the concentration of endothelin, nitric oxide and the expression of endothelin, endothelial nitric oxide synthase mRNA in experimental hyperlipidemia model

目的 观察在高脂血症动物模型形成过程中不同程度的高血脂以及DDPH对动脉血中NO、ET 1含量以及动脉壁eNOS、内皮素 1基因表达的影响。方法 在实验性家兔高脂血症模型基础上 ,采用半定量逆转录多聚酶链式反应(RT PCR)等技术 ,观察了不同时期的高脂血症对内皮素及一氧化氮代谢的影响以及DDPH的干预作用。结果 不同时期的高脂饮食可造成不同程度的高脂血症 ,相应的血管内皮细胞的内皮素 1和一氧化氮的代谢紊乱也有所不同 :轻、中度高脂血症可引起eNOS及内皮素 1mRNA表达水平升高和外周血ET 1含量增高 ;而重度高脂血症可引起eNOS及内皮素mRNA表达水平下降和外周血NOP、ET 1浓度降低 ;DDPH(ig)可明显降低实验性家兔的高血脂 ,并同时促进一氧化氮代谢产物 (NOP)、ET 1含量的升高和eNOS、ET 1mRNA的表达。结论 不同程度的高脂血症对血管内皮活性物质及其基因表达的影响是不同的。DDPH可保护血管内皮细胞 ,恢复血管活性物质合成和释放 。

AIM To observe the effects of different degrees of hyperlipidemia on the concentration of NO and ET 1 in the aortic blood and gene expression of endothelin 1 and endothelial synthase in aorta, simultaneously, examine the mechanism of DDPH in the protection of endothelium of vascular vessel. METHODS On the basis of experimental hyperlipidemia models, the mRNA level of endothelial nitric oxide synthase (eNOS) and endothelin 1 in rabbit aortic vessel were examined by quantitative reverse transcription polymerase chain reaction (RT PCR), simultaneously, the concentration of plasma endothelin 1 and nitric oxide production (NOP) were measured in six groups which were divided by various span of hyperlipidemic feeding. In addition, we also studied the effect of DDPH (ig) on the metabolism of nitric oxide and endothelin 1. RESULTS Various degrees of hyperlipidemia resulting from different period hyperlipidemic feeding caused different metabolic disorders of endothelin 1 and nitric oxide in vascular endothelial cells: in the early or middle period of hyperlipidemia, the mRNA level of eNOS and endothelin 1 in aortic vessel and the concentration of ET 1 in peripheral blood increased significantly comparing with that in control group; in the late period of hyperlipidemia, both the mRNA level of eNOS and endothelin 1 and the content of NOP and ET 1 decreased markedly comparing with that in control group; DDPH could reduce significantly the level of lipid, and promoted the expression of eNOS, ET 1 gene and the synthesis of NOP and ET 1. CONCLUSION Different degrees of hyperlipidemia had different effects on the synthesis and gene expression of endothelial vasomotory material. DDPH could partly reverse the impairment of ET 1 and NO system, resumed the synthesis, release of vasomotory material in endothelium and thereby protected the endothelium and its vasoreactivity.