Pan Si-Yuan, Dong Hang, Han Yi-Fan, Li Wen-Yuan, Zhao Xing-Ye, Ko Kam-Ming
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, China.
Eur J Pharmacol. 2006 May 10;537(1-3):200-4. doi: 10.1016/j.ejphar.2006.03.001. Epub 2006 Mar 10.
Mice were intragastrically treated with single doses (0.05-0.8 g/kg) of schisandrin B (a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis). Twenty-four hours after schisandrin B administration, the serum triglyceride level was increased by 10-235% in a dose-dependent manner. However, the serum low density lipoprotein cholesterol level was significantly decreased by 28% at a dose of 0.8 g/kg. When given once daily (0.01-0.2 g/kg) for 4 days, schisandrin B also dose-dependently elevated the serum triglyceride level (17-134%). Kinetics parameters estimated by Scott's plot analysis of schisandrin B-induced changes in serum and hepatic triglyceride levels were determined: serum-E(max) (maximal effect)=6 mmol/L (384% increase, P<0.001); K(D) (affinity)=0.59 mmol/kg; pD(2) (an index of affinity)=6.62; liver-E(max)=21 micromol/g (68% increase, P<0.001); K(D)=0.37 mmol/kg; pD(2)=6.83. The efficacy of schisandrin B in increasing the triglyceride level was 5.6-fold higher in serum than in liver tissue. Fenofibrate (0.2g/kg) treatment, when in combination with schisandrin B (0.2g/kg), for 4 days significantly reduced the schisandrin B-induced increase in serum triglyceride level (by 81%, P<0.001). Hepatic triglyceride level was also decreased (by 100%, P<0.001) by co-treatment with fenofibrate. Our results suggest that schisandrin B treatment can be used to establish a mouse model of acute hypertrigylceridemia.
用单剂量（0.05 - 0.8 g/kg）的五味子醇甲（从五味子果实中分离出的一种二苯并环辛二烯衍生物）对小鼠进行灌胃处理。给予五味子醇甲24小时后，血清甘油三酯水平以剂量依赖性方式升高了10% - 235%。然而，在剂量为0.8 g/kg时，血清低密度脂蛋白胆固醇水平显著降低了28%。当每天一次（0.01 - 0.2 g/kg）给予4天时，五味子醇甲也剂量依赖性地升高了血清甘油三酯水平（17% - 134%）。通过对五味子醇甲诱导的血清和肝脏甘油三酯水平变化进行Scott作图分析，确定了动力学参数：血清 - E(max)（最大效应）=6 mmol/L（增加384%，P<0.001）；K(D)（亲和力）=0.59 mmol/kg；pD(2)（亲和力指数）=6.62；肝脏 - E(max)=21 μmol/g（增加68%，P<0.001）；K(D)=0.37 mmol/kg；pD(2)=6.83。五味子醇甲升高甘油三酯水平的效力在血清中比在肝脏组织中高5.6倍。非诺贝特（0.2g/kg）与五味子醇甲（0.2g/kg）联合处理4天，显著降低了五味子醇甲诱导的血清甘油三酯水平升高（降低81%，P<0.001）。联合非诺贝特处理也降低了肝脏甘油三酯水平（降低100%，P<0.001）。我们的结果表明，五味子醇甲处理可用于建立急性高甘油三酯血症小鼠模型。
