小檗碱对兔血脂代谢及维生素D受体和胰岛素诱导基因2基因表达的影响

Effects of berberine on lipid metabolism and vitamin D receptor as well as insulin-induced gene 2 gene expression of rabbits

目的研究小檗碱对高脂模型兔血脂代谢的影响,并探讨其调血脂作用是否与维生素D受体(vitamin D receptor,VDR)、胰岛素诱导基因2(insulin-induced gene 2,Insig-2)的表达变化有关。方法雄性新西兰大耳白兔40只随机分为对照组、模型组、阳性药非诺贝特(30 mg/kg)组和小檗碱低、高剂量(28、112 mg/kg)组。兔喂饲高脂饲料8周建立高脂模型,给药8周后测定各组兔血清中总胆固醇(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)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)和脂蛋白a(LPa)等指标的水平。RT-PCR法检测脂肪组织中VDR和Insig-2基因表达的变化。结果与对照组比较,模型组兔血清TC、TG、LDL-C、ApoB及LPa水平明显升高(P<0.05),而ApoA1水平则明显降低(P<0.05);经小檗碱处理后,兔血清中TC、TG、LDL-C、ApoB及LPa的水平较模型组显著降低(P<0.05),同时ApoA1水平则明显升高(P<0.05);RT-PCR检测结果显示,小檗碱干预后兔脂肪组织中VDR、Insig-2 mRNA的表达较模型组显著升高(P<0.05),且低剂量小檗碱的效果更明显。结论小檗碱具有明显的调血脂作用,其机制可能是通过上调脂肪组织VDR和Insig-2 mRNA表达来实现的。

Objective To investigate the effects of berberine on lipids metabolism of hyper-lipidemic rabbits and to explore whether its mechanism was involved in the vitamin D receptor （VDR） gene and insulin-induced gene 2 （Insig-2） gene expressions in adipose. Methods Forty male New Zealand white rabbits were randomly divided into five groups： normal diet （ND）, high-fat diet （HFD）; high-fat diet ＋ pretreatments of either Fenofibrate （30 mg/kg） or berberine low dose （28 mg/kg, BLD）, and berberine high dose （112 mg/kg, BHD） groups. The serum TC, TG, LDL-C, HDL-C, ApoA1, ApoB, and LPa in each different treated rabbit group were determined after 8-week administration. The mRNA expressions of VDR and Insig-2 in adipose tissue were quantified by RT-PCR. Results Compared with normal diet group, the serum TC, TC- LDL-C, ApoB, and LPa in high fat diet group obviously elevated （P 〈 0.05）, while ApoA1 obviously descend （P 〈 0.05）. Compared with the high fat diet group, the levels of serum TC, TC- LDL-C, ApoB, and LPa in berberine treated group were significantly decreased （P 〈 0.05）, while ApoA1 was elevated obviously （P 〈 0.05）. The result of RT-PCR demonstrated that the mRNA expressions of VDR and Insig-2 in high fat diet group were significantly higher than those of the normal diet group （P 〈 0.05）, and the VDR and Insig-2 rnRNA expressions were significantly up-regulated by berberine （P 〈 0,05）, especially in BLD. Conclusion Berberine could significantly decrease the levels of blood lipids of the hyperlipidemic rabbits, the mechanism may be related to elevating the expressions of VDR and Insig-2 gene.