中文摘要：

目的 探讨氧化苦参碱对高脂饮食诱导载脂蛋白E（ApoE）基因敲除（ApoE^（-/-））小鼠模型肝脏胆固醇代谢调控基因的影响。方法 2014年4月—2015年1月,将17只SPF级C57BL/6J小鼠作为正常组（NC组）,给予基础饲料饲养;68只SPF级ApoE^（-/-）小鼠给予高脂饲料饲养;均喂养16周后,再将高脂饲料喂养的ApoE^（-/-）小鼠按照随机数字表法分为胰岛素抵抗模型组（IR组）、氧化苦参碱低剂量组（OXYL组）、氧化苦参碱中剂量组（OXYM组）、氧化苦参碱高剂量组（OXYH组）,每组17只,OXYL、OXYM、OXYH组分别给予氧化苦参碱25 mg·kg^（-1）·d^（-1）、50mg·kg^（-1）·d^（-1）、100 mg·kg^（-1）·d^（-1）连续灌胃8周,各组实验过程中均给予等体积的纯水。分别检测各组小鼠葡萄糖输注率（GIR）,空腹血糖（FBG）水平,血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平,空腹胰岛素（FINS）水平,并计算胰岛素抵抗指数（HOMA-IR）,并检测肝脏组织TC水平。采用RT-q PCR和Western blotting法检测肝脏组织固醇调节元件结合蛋白-2（SREBP-2）、固醇调节元件结合蛋白裂解激活蛋白（SCAP）、胰岛素诱导基因-2（INSIG2）、羟甲基戊二酸单酚辅酶A还原酶（HMGCR）、低密度脂蛋白受体（LDLr）mRNA及其蛋白水平。结果 IR组FBG水平,血清TC、TG、LDL-C、HDL-C水平均高于NC组（P〈0.05）;OXYL组血清TC、TG、LDL-C、HDL-C水平均低于IR组,OXYM、OXYH组FBG水平,血清TC、TG、LDL-C、HDL-C水平均低于IR组（P〈0.05）。IR组GIR低于NC组,OXYL组、OXYM组、OXYH组GIR均高于IR组（P〈0.05）。IR组FINS水平、HOMA-IR均高于NC组（P〈0.05）;OXYL组HOMA-IR低于IR组（P〈0.05）;OXYM、OXYH组FINS水平、HOMA-IR均低于IR组（P〈0.05）。IR组肝脏组织SREBP-2、HMGCR、LDLr mRNA及其蛋白水平低于NC组,SCAP、INSIG2 mRNA及其蛋白水平高于NC组

英文摘要：

Objective To investigate the effect of oxymatrine on genes regulated hepatic cholesterol metabolism in ApoE -/- mice induced by high fat diet. Methods From April 2014 to January 2015, seventeen SPF grade C57BL/6J mice were selected as normal control （NC） group and fed on the basal diet. Sixty - eight SPF grade ApoE-/- mice fed on high fat diet. After 16 weeks of feeding, according to the random number table method, ApoE-/- mice were averagely divided into insulin resistance model group （ 1R group）, low oxymatrine dose group （ OXYL group）, middle oxymatrine dose group （ OXYM group） and high oxymatrine dose group （OXYH group） . There were seventeen mice in each group. In OXYL group, OXYM group and OXYH group, 25 mg·kg-1· d-1, 50 mg·kg-1· d-1and 100mg·kg-1· d-1 oxymatrine were given by continuous oral garage for 8 weeks, and all groups were given equal volume of pure water. Glucose infusion rate （GIR）, blood glucose （FBG） level, serum leves of total cholesterol （ TC）, three glycerol （ TG）, low density lipoprotein cholesterol （ LDL-C）, high density lipoprotein cholesterol （HDL-C）, fasting insulin （FINS） level in each group of mice were measured, and the insulin resistance index （HOMA- IR） was calculated, and the TC level of liver tissue was detected. The expression of SREBP-2, SCAP, INSIG2, HMGCR and LDLr mRNA and its protein were detected using RT- qPCR and western -blotting methods in mice liver tissue. Results The FBG level, serum levels of TC, TG, LDL-C and HDL-C in IR group was significantly higher than NC group （P 〈 0.05） . The serum levels of TC, TG, LDL-C and HDL-C in OXYL group was significantly lower than IR group （ P 〈 0.05） . The FBG level, serum levels of TC, TG, LDL-C and HDL-C of in OXYM and OXYH group were significantly lower than IR group （ P 〈 0. 05） , CIR. in iR group was lower than NC group （ P 〈l）. 05 ） ; FiR in OXYL group, OXYI-I group and OXYM group was higher than IR group （ P 〈 0.05 ） ; The FINS level a