新化合物哌芳安他抗大鼠和兔动脉粥样硬化作用机理的初步研究

目的在早期和晚期动脉粥样硬化模型上研究新化合物哌芳安他抗动脉粥样硬化的机制.方法大鼠或家兔随机分为正常对照、模型对照和哌芳安他给药组,其中模型对照和哌芳安他给药组动物给予高胆固醇饲料,检测的指标包括:兔颈动脉HE染色;大鼠或兔血清TC, LDL-CHO, HDL-CHO, IL-8, ET-1, PGI2, TXA2 和NO水平;兔颈动脉MCP-1和 IL-8 mRNA表达量.结果哌芳安他能明显抑制早期和晚期动脉粥样硬化中TXA2的过量表达,在大鼠早期动脉粥样硬化中可见哌芳安他给药组动物血清NO增加而IL-8含量减少;在兔晚期动脉粥样硬化中可见IL-8和MCP-1 mRNA表达降低;哌芳安他对血脂水平、MDA 和SOD无明显影响.结论哌芳安他抗动脉粥样硬化机制与其升高血清NO水平,降低TXA2含量及抑制IL-8 和MCP-1过度表达相关.

Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis

AimTo investigate the anti-atherosclerotic mec hanisms of the novel compound pivanampeta in the early and later stages of ather osclerosis evolution. MethodsRats or rabbits were random ly assigned to the control, the model and the pivanampeta-treated groups. The r ats or rabbits in the model group and the pivan ampeta-treated group were fed with hypercholesterol diet. The carotids of rabb i ts were cut into pieces and stained with HE. The rat or rabbit serum levels of T C, LDL-CHO, HDL-CHO, IL-8, ET-1, PGI 2, TXA 2, and NO were assayed. The ex pres sions of MCP-1 and IL-8 mRNA on rabbit carotid were determined by semi-quanti tat ive RT-PCR. ResultsPivanampeta exerted an inhibitory ef f ect on TXA 2 formation without PGI 2 production in the early and later stages of atherosclerosis. The significantly increased release of NO and the decreased re lease of IL-8 in the animals in pivanampeta-treated group were both detected i n the rat atherosclerosis model. In the rabbit atherosclerosis model the expressio ns of IL-8 and MCP-1 mRNA in pivanampeta-treated group were decreased signifi can tly. However, the treatment with pivanampeta had no effect on the levels of plas ma cholesterol, MDA and SOD. ConclusionThe increase of s erum NO contents and the decrease of plasma TXA 2 level, as well as its inhibit ion of expression of IL-8 and MCP-1 are probably involved in the mechanisms un derlying the anti-atherosclerotic effects of pivanampeta.