The effects of berberine on hyperhomocysteinemia and hyperlipidemia in rats fed with a long-term high-fat diet.

The effects of berberine on hyperhomocysteinemia and hyperlipidemia in rats fed with a long-term high-fat diet.
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小檗碱对长期高脂饮食大鼠高同型半胱氨酸血症和高脂血症的影响

DOI:
10.1186/1476-511x-11-86
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发表时间:
2012-07-04
影响因子:
4.5
通讯作者:
Gao X
Gao X
中科院分区:
医学3区
文献类型:
--
作者:
Chang XX;Yan HM;Xu Q;Xia MF;Bian H;Zhu TF;Gao X

文献摘要

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本研究观察了小檗碱(BBR)对长期高脂饮食(HFD)喂养的SD大鼠血清同型半胱氨酸(Hcy)、血脂及主动脉病变的影响。健康雄性SD大鼠,体重190-210 g,随机分为标准饲料组和高脂饲料组,每组24周。喂饲8周后,随机分为小檗碱组(200 mg · kg-1·d-1)和溶媒组(200 mg · kg-1·d-1)。禁食过夜后处死大鼠,取血测定空腹血清同型半胱氨酸(Hcy)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-c)水平。主动脉行HE染色和苏丹红染色,观察主动脉病变程度。将肝脏解剖并在液氮中快速冷冻,用于肝脏TC含量和分子分析。实时荧光定量PCR检测肝脏3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR)、脂蛋白受体和载脂蛋白基因表达。黄连素灌胃16周可降低高脂饮食大鼠的血清Hcy水平。同时,它还降低了体重,改善了血清TC和LDL-c。黄连素也倾向于降低肝脏胆固醇。小檗碱还可上调LDL受体(LDLR)mRNA水平,抑制HMGR基因表达。同时,小檗碱处理组大鼠肝脏载脂蛋白E(apoE)mRNA表达显著增加,而apoAI和清道夫受体(SR)mRNA表达无明显变化。此外,小檗碱治疗大鼠16周未出现动脉粥样硬化病变。黄连素可通过上调LDLR和apoE mRNA水平,抑制HMGR基因表达,部分对抗HFD引起的高同型半胱氨酸血症和高脂血症。
The study was undertaken to examine the effects of berberine (BBR) on serum homocysteine, lipids and the aortic lesion in Sprague–Dawley (SD) rats fed with a long-term high-fat diet (HFD). Healthy male SD rats weighing 190-210 g received randomly standard diet or a high-fat diet for 24 weeks. After 8 weeks of feeding, rats fed with HFD were randomized to receive berberine (200 mg · kg-1· day-1) or vehicle by gavage for 16 weeks. After overnight fasting, all rats were sacrificed and total blood samples were also collected for determinant of fasting serum homocysteine (Hcy), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) levels. The aorta was stained with hematoxylin and eosin (HE) and Sudan Ш to evaluate aortic lesion. The livers were dissected out and snap-frozen in liquid nitrogen for hepatic TC content and molecular analysis. 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), Lipoprotein receptors and apolipoproteins gene expression in the liver were determined by real-time PCR. Intragastrical administration with berberine for 16 weeks lowered serum Hcy in rats fed with a high-fat diet. In parallel, it also decreased body weight and improved serum TC and LDL-c. Berberine also tended to decrease hepatic cholesterol. Consistently, berberine also upregulated LDL receptor (LDLR) mRNA level and suppressed HMGR gene expression. Meanwhile, upon berberine-treated rats, there was a significant increase in apolipoprotein E (apoE) mRNA, but no change in apoAI and scavenger receptor (SR) mRNA in the liver. Further, no atherosclerotic lesions were developed in berberine-treated rats for 16 weeks. Berberine can counteract HFD-elicited hyperhomocysteinemia and hyperlipidemia partially via upregulating LDLR and apoE mRNA levels and suppressing HMGR gene expression.