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很多研究表明血浆血清C-反应蛋白(CRP)预告健康人及冠心病患者的心血管事件,提示它可能在动脉粥样硬化的发生中起一定作用。然而我们利用易于发生动脉粥样硬化的apoE基因敲除的小鼠模型,转基因使之表达人CRP,发现此种转基因雄性小鼠生存至第56周时,CRP并不影响自发性动脉粥样硬化的发生、进展或严重程度,亦不影响死亡率及罹患率。尽管雌性apoE-/-小鼠发生动脉粥样硬化的时间比雄性小鼠更快,转基因表达的人CRP受到性激素调控,且仅在雄性小鼠中的表达水平与人相同。因此本研究仅在雄性小鼠中进行。小鼠血清amyloidP成分,一个炎症反应的极敏感标志物,在整个实验过程中未发生改变,提示该小鼠模型发生动脉粥样硬化的机制与急性炎症反应无关。与野生型对照小鼠比较,转CRP基因的apoE-/-小鼠血中CRP浓度较高,而且高CRP水平与低estradiol浓度相关,表明在apoE-/-小鼠中转入的人CRP基因表达上调,与改变的雌激素水平有关。因此,该研究结果表明炎症标志CRP可能并不参与动脉粥样硬化的发生,即既不促进动脉粥样硬化,亦不保护机体不发生动脉粥样硬化。但作者又指出,本研究中的转入的人CRP基因,它所处的环境是鼠的脂蛋白、鼠的补体和细胞外基质,鼠的组织和炎症,鼠的细胞因子、介质和细胞受体,而不是人的,所以不宜将此模型或类似模型的结论推广应用于人体。
Many studies have shown that plasma serum C-reactive protein (CRP) to predict cardiovascular events in healthy people and patients with coronary heart disease, suggesting that it may play a role in the development of atherosclerosis. However, we used a mouse model of apoE gene knock-out prone to atherosclerosis to express human CRP. We found that CRP did not affect spontaneous atherosclerosis The occurrence, progress or severity of the disease does not affect the mortality and the rate of attack. Although atherosclerosis occurs more frequently in female apoE - / - mice than in male mice, the transgene expressed human CRP is regulated by sex hormones and is expressed in the same manner in humans only in male mice. Therefore, this study was performed in male mice only. The serum amyloidP component of mouse serum, a very sensitive marker of inflammation, remained unchanged throughout the experiment, suggesting that the mechanism of atherosclerosis in this mouse model is not related to the acute inflammatory response. Compared to wild-type control mice, CRP concentrations were higher in apoE - / - mice transfected with the CRP gene, and high CRP levels correlated with lower estradiol concentrations, indicating that the human CRP gene transfected in apoE - / - mice The expression is up-regulated, which is related to the changed estrogen level. Therefore, the results of this study suggest that the inflammatory marker CRP may not be involved in the development of atherosclerosis, that is, it neither promotes atherosclerosis nor protects the body from atherosclerosis. However, the authors note that the human CRP gene introduced in this study is in the context of murine lipoproteins, murine complement and extracellular matrix, murine tissue and inflammation, murine cytokines, media and cellular receptors Body, not human, so it is not appropriate to apply the conclusion of this model or similar model to the human body.