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本文检测了Gemfibrozil(GF,商品名Lopid降脂灵是一种常用的抗动脉硬化药物,具有降低甘油三脂和升高高密度脂蛋白(HDL)的作用)对肝细胞载脂蛋白AI的合成与分泌的作用以及可能的作用机制。在本研究中我们使用了ELISA,免疫沉淀、分子生物学技术(如mRNA定量、半寿期和新mRNA合成率等)和特异性抗体。结果发现,GF可增加载脂蛋白AI(apoAI)的分泌及放射标记蛋氨酸的掺入(合成)。与对照组相比使用200μm的GF可以增加apoAI的分泌及合成分别达158%和130%(短期冲击)。分子生物学结果显示,使用不同浓度的GF可以增加稳定状态的mRNA表达(最高达204%)。mRNA的半寿期由14.5h延长到35h。而新的mRNA的合成率无变化。结论:GF的心脏保护作用是因为该药刺激肝脏增加apoAI的合成及分泌。其机制则为延长apoAImRNA的半寿期从使mRNA在肝细胞内的含量增加,而与新的mRNA的生成无关。
This article examined the effect of Gemfibrozil (GF, a trade name Lopid lowering lipid, a commonly used antiatherosclerotic drug with the effect of lowering triglycerides and increasing high density lipoprotein (HDL)) on hepatocyte apolipoprotein AI And secretion of the role and possible mechanism of action. In this study we used ELISA, immunoprecipitation, molecular biology techniques such as mRNA quantitation, half-life and rate of new mRNA synthesis, and specific antibodies. As a result, GF was found to increase the secretion of apolipoprotein AI (apoAI) and the incorporation of radiolabeled methionine (synthesis). The use of 200 μm GF increased the secretion and synthesis of apoAI by 158% and 130%, respectively (short-term impact) compared to the control group. Molecular biology results show that using different concentrations of GF can increase steady-state mRNA expression (up to 204%). The half-life of mRNA was extended from 14.5 h to 35 h. The new mRNA synthesis rate unchanged. CONCLUSION: The cardioprotective effect of GF is due to the drug stimulating the liver to increase the synthesis and secretion of apoAI. The mechanism is to prolong the half-life of apoAI mRNA from increasing the content of mRNA in hepatocytes, but not with the generation of new mRNA.