苏晴+邓小飞++周人杰

[摘要] 目的 探讨脂蛋白酯酶在compound K调节血脂水平中的作用。 方法 36只雄性SD大鼠随机分为6组，除对照组外均给予高脂饮食，对照组和模型组给予生理盐水腹腔注射，compound K给药组分别给予compound K 1、3、9 mg/kg腹腔注射，GGPP组同时给予compound K 3、9 mg/kg GGPP。4周后处死动物，取样测定血脂、肝素后脂蛋白酯酶活性、脂蛋白酯酶表达水平等；培养大鼠肝细胞株BRL，分别给予compound K 3、10、30 μmol/L处理12 h后，检测脂蛋白酯酶表达水平。 结果 与模型组比较，compound K 3、9 mg/kg组的总胆固醇、低密度脂蛋白胆固醇、三酰甘油显著降低，高密度脂蛋白胆固醇、肝素后血清脂蛋白酯酶活性和脂蛋白酯酶表达量显著增高，差异有统计学意义（P < 0.05），且呈剂量依赖性。体外细胞试验结果与动物实验一致。 结论 compound K能够通过增加脂蛋白酯酶的表达和活性达到降低高脂饮食大鼠血清三酰甘油的作用，其机制与compound K激活肝X受体α相关。

[关键词] compound K；动脉粥样硬化；脂蛋白酯酶；肝X受体α

[中图分类号] R543 [文献标识码] A [文章编号] 1673-7210（2017）01（b）-0020-05

Role of lipoprotein lipase on serum lipid modulation of compound K

SU Qing DENG Xiaofei ZHOU Renjie

Department of Emergency， Xinqiao Hospital， the Third Military Medical University of PLA， Chongqing 400037， China

[Abstract] Objective To explore the role of lipoprotein lipase （LPL） on serum lipid modulation of compound K. Methods 36 male SD rats were divided into 6 groups. All animals were fed with high fat diet except control group. Control group and model group were given intraperitoneal injection of saline. compound K groups were treated with different doses of compound K （1， 3， 9 mg/kg）. GGPP group was administrated with compound K 3 and 9 mg/kg GGPP simultaneously. After 4 weeks， animals were sacrificed. Serum lipid profile， LPL activity and the expression of LPL mRNA and protein were measured. BRL cells were treated with different doses of compound K （3， 10， 30 μmol/L） for 12 h， and the expression levels of LPL were measured. Results Compared with model group， total cholesterol， low-density lipoprotein cholesterol and triglycerides levels of compound K 3 and 9 mg/kg groups were significantly decreased， high density lipoprotein cholesterol， serum lipoprotein lipase activity after heparin and LPL expression of compound K 3 and 9 mg/kg groups were significantly increased， with statistical differences （P < 0.05）， and the action depended on its dose. The results of in vitro cell experiments were consistent with animal experiments. Conclusion compound K can reduce the expression of serum triglyceride via up-regulation of LPL expression and activity， and the mechanism is associated with compound K activated liver X receptor α.

[Key words] compound K； Atherosclerosis； Lipoprotein lipase； Liver X receptor α

近年來，因动脉粥样硬化导致的心肌梗死、中风等多种严重心脑血管疾病引发的死亡人数居各类疾病之首[1]。在目前广泛采取防治措施的情况下，动脉粥样硬化的发病率并没有出现显著的下降，提示现有防治手段尚待改进，并亟需作用于新靶点的动脉粥样硬化防治药物。compound K是二醇型人参皂苷经过消化代谢后产生并吸收入血液循环的活性物[2-3]，具有多种药理学活性。近期有研究证实，compound K能够通过激活肝X受体α（liver X receptor α，LXRα）达到调节血脂和抗炎的作用，从而延缓实验动物动脉粥样硬化的形成[4]。

compound K作用靶点与现有调节血脂药物不同，其机制也不相同。但目前的研究只关注了胆固醇逆转运通路的变化，解释了低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）水平变化的机制，但对于三酰甘油（triglyceride，TG）水平变化的机制尚缺乏探讨[4]。……