Zhao Shui-Ping, Li Rong, Dai Wen, Yu Bi-Lian, Chen Lu-Zhu, Huang Xian-Sheng
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
PLoS One. 2017 Sep 21;12(9):e0184949. doi: 10.1371/journal.pone.0184949. eCollection 2017.
Xuezhikang (XZK), an extract of Chinese red yeast rice, is recommended as an optimal choice for patients with coronary heart disease (CHD) with markedly elevated triglyceride (TG) levels. This study was designed to compare the hypotriglyceridemic effects between XZK and simvastatin. The role of apolipoprotein A5 (apoA5), a key regulator of TG metabolism and a target gene of peroxisome proliferator-activated receptor α (PPARα), was to be identified in XZK-related hypotriglyceridemic actions. For these goals, hypertriglyceridemia of rats was induced by a high-fructose diet. In order to investigate the hypotriglyceridemic effects of XZK and simvastatin on these animals based on an equivalent low-density lipoprotein cholesterol (LDL-C) lowering power, we titrated their doses (XZK 80 mg/kg/d versus simvastatin 1 mg/kg/d) according to plasma LDL-C reduction of rats. Similarly, we titrated the target doses of the two agents (XZK 500 μg/ml versus simvastatin 10 μM) according to hepatocyte LDL receptor expressions, and then compared the effects of the two agents on TG and apoA5 of hepatocytes in vitro. Our results showed that XZK (80 mg/kg/d) had higher hypotriglyceridemic performance than simvastatin (1 mg/kg/d) on these animals albeit their equivalent LDL-C lowering power. Higher plasma apoA5 levels and hepatic apoA5 expressions were observed in rats treated with XZK (80 mg/kg/d) than simvastatin (1 mg/kg/d). Further, XZK (80 mg/kg/d) contributed to higher hepatic PPARα expressions of rats than simvastatin (1 mg/kg/d). Although the two agents led to an equivalent up-regulation of LDL receptors of hepatocytes, more TG reduction and apoA5 elevation were detected in hepatocytes treated with XZK (500 μg/ml) than simvastatin (10 μM). However, PPARα knockdown eliminated the above effects of XZK on hepatocytes. Therefore, our study indicates that XZK has greater hypotriglyceridemic performance than simvastatin in the setting of an equivalent LDL-C lowering power, which is attributed to more apoA5 up-regulation by this agent via the PPARα signaling pathway.
血脂康（XZK）是一种从中国红曲米中提取的物质，被推荐为甘油三酯（TG）水平显著升高的冠心病（CHD）患者的最佳选择。本研究旨在比较血脂康与辛伐他汀的降甘油三酯效果。载脂蛋白A5（apoA5）是TG代谢的关键调节因子，也是过氧化物酶体增殖物激活受体α（PPARα）的靶基因，其在血脂康相关的降甘油三酯作用中的作用有待确定。为实现这些目标，通过高果糖饮食诱导大鼠出现高甘油三酯血症。为基于等效的低密度脂蛋白胆固醇（LDL-C）降低能力研究血脂康和辛伐他汀对这些动物的降甘油三酯效果，我们根据大鼠血浆LDL-C降低情况滴定它们的剂量（血脂康80毫克/千克/天，辛伐他汀1毫克/千克/天）。同样，我们根据肝细胞LDL受体表达滴定两种药物的目标剂量（血脂康500微克/毫升，辛伐他汀10微摩尔），然后在体外比较两种药物对肝细胞TG和apoA5的影响。我们的结果表明，尽管血脂康（80毫克/千克/天）和辛伐他汀（1毫克/千克/天）降低LDL-C的能力相当，但血脂康在这些动物上的降甘油三酯性能更高。与辛伐他汀（1毫克/千克/天）治疗的大鼠相比，血脂康（80毫克/千克/天）治疗的大鼠血浆apoA5水平和肝脏apoA5表达更高。此外，血脂康（80毫克/千克/天）使大鼠肝脏PPARα表达高于辛伐他汀（1毫克/千克/天）。尽管两种药物导致肝细胞LDL受体的上调程度相当，但与辛伐他汀（10微摩尔）相比，血脂康（500微克/毫升）处理的肝细胞中检测到更多的TG降低和apoA5升高。然而，PPARα基因敲除消除了血脂康对肝细胞的上述作用。因此，我们的研究表明，在等效的LDL-C降低能力情况下，血脂康的降甘油三酯性能比辛伐他汀更强，这归因于该药物通过PPARα信号通路使apoA5上调更多。
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