新型siRNA药物：Inclisiran在降脂治疗中的研究进展

摘要/Abstract

摘要： 在心血管疾病的危险因素中，脂质代谢失调是最常见和最危险的因素之一，因而降脂治疗在减少心血管疾病发病率和死亡率方面具有重要意义。Inclisiran是一种以前蛋白转化酶枯草溶菌素9（PCSK9）为靶点的新型小干扰RNA（siRNA）药物。Inclisiran复合物能特异性结合PCSK9的信使RNA，阻断PCSK9蛋白质的合成，促进低密度脂蛋白受体的再循环，增加血液中低密度脂蛋白胆固醇（LDL-C）的再摄取和降解，从而降低LDL-C水平。Inclisiran是一种高效、长效、不良反应少的新型降脂药物，每年两次给药可使血中LDL-C水平下降50%以上，为降脂治疗带来了新的选择。通过查阅近年来国内外相关文献，本文对Inclisiran的化学结构、药理作用机制、在降脂方面的药物临床试验及安全性研究等方面的研究进行综述。

关键词: font-size:medium, ">Inclisiran；降脂治疗；小干扰RNA；前蛋白转化酶枯草溶菌素9；低密度脂蛋白胆固醇

Abstract: Dyslipidemia is one of the main risk factors of cardiovascular diseases. Lipid-lowering therapy plays an important role in reducing the morbidity and mortality of cardiovascular diseases. Inclisiran is a new tpye of small interfering RNA(siRNA) drugs， which can specifically bind to the corresponding messenger-RNA(mRNA) of the target-protein PCSK9， suppress PCSK9 protein synthesis， and elevates LDL-R recycling， increase the reuptake and degradation of low-density lipoprotein cholesterol(LDL-C) in the blood， thereby reducing LDL-C levels. About 50% reduction in low-density lipoprotein cholesterol levels have been observed in randomized controlled trials without severe adverse reactions. Inclisiran may provide substantial LDL-C lowering benefits and provide new option for lipid-lowering treatments. In this study the chemical construction， pharmacological mechanism， clinical trials in lipid lowering and safety studies of Inclisiran were reviewed.

Key words: font-size:medium, ">Inclisiran； Lipid-lowering therapy； siRNA； PCSK9； LDL-C

中图分类号:

侯立强, 孙燕, 任雷, 邢俊香, 陈萍. 新型siRNA药物：Inclisiran在降脂治疗中的研究进展[J]. 中国医药导刊, 2023, 25(2): 140-145.

HOU Liqiang, SUN Yan, REN Lei, XING Junxiang, CHEN Ping. Research Progress of A New siRNA Drug： Inclisiran for LDL-Cholesterol Lowering Treatment[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2023, 25(2): 140-145.

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