小檗碱对脂代谢及血管粥样硬化的影响及机制探讨

Effects of Berberine on lipid metabolism and atherosclerosis in hyperlipidemic rabbits and its mechanism

摘要:

目的：研究小檗碱（Berberine，Ber）对高脂兔模型脂代谢和血管硬化的影响，并探讨其可能的作用机制。方法：采用高脂饲料喂养2月建立高脂兔动物模型。40只新西兰大耳白兔随机分成普通饲料组（普食组）、高脂模型组、高脂+Ｂer组[28、112 mg/（kg·d）]、高脂+非诺贝特组[30 mg/（kg·d）]。2月后测定各组血清总胆固醇（Total cholesterol，TC）、三酰基甘油（Triglycerides，TG）、低密度脂蛋白胆固醇（Low density lipoprotein-cholesterol，LDL-C）、高密度脂蛋白胆固醇（High density lipoprotein-choles－terol，HDL-C）水平；HE染色观察主动脉组织形态学变化；实时荧光定量PCR检测主动脉诱导型一氧化氮合酶（Inductible nitric oxide synthase，iNOS）和B类1型清道夫受体（Scavenger receptor class-B type 1，SR-B1）基因表达的变化。结果：与普食组相比，高脂模型组 TC、TG和LDL-C水平显著升高（P<0.05），主动脉内膜出现明显的脂质沉积和泡沫细胞形成，iNOS和SR-B1 mR－NA表达显著升高（P<0.05）；与高脂模型组相比，高脂＋Ber处理组血清TC、TG和LDL-C的水平显著降低（P<0.05），而HDL水平显著升高（P<0.05），主动脉粥内膜脂质沉积减轻，泡沫细胞明显减少，iNOS和SR-B1 mRNA表达显著降低（P<0.05）。结论：Ber具有明显的调血脂和抗血管硬化作用，其作用机制与抑制iNOS和SR-B1基因表达相关。

Abstract:

Objective：To investigate the effects of Berberine（Ber） on lipids metabolism and atherosclerosis in hyperlipidemic rabbits and to study the possible mechanism. Methods：The hyperlipidemic rabbit model was established by feeding high fat diet for 2 months. 40 New-Zealand rabbits were randomly divided into control group，high fat diet model group，high fat diet and Ber treated group[28，112 mg/（kg·d）]，high fat diet and Fenofibrate treated group[30 mg/（kg·d）]. The levels of serum total cholesterol（TC），triglycerides（TG），low density lipoprotein-cholesterol（LDL-C） and high density lipoprotein-cholesterol（HDL-C） were determined after 2 months，pathomorphological changes of aortic arteries was observed and inductible nitric oxide synthase（iNOS） and scavenger receptor class-B type 1（SR-B1） mRNA expression in aortic tissue were quantified by quantitative real time PCR. Results：The levels of serum TC，TG and LDL-C were obviously elevated（P<0.05），apparent atherosclerotic plaque was observed in aortic arteries and iNOS and SR-B1 mRNA expressions were obviously increased（P<0.05） in high fat diet group compared with those in control group. Serum TC，TG and LDL-C levels were decreased（P<0.05），HDL-C level was increased（P<0.05），degree of aortic atherosclerosis was mitigated，foam cells were reduced and iNOS activity and SR-B1 mRNA expressions were reduced（P<0.05） in high fat diet and Ber treated group than in high fat diet model group. Conclusions：Ber can obviously reduce the blood lipid levels and aortic atherosclerosis in the hyperlipidemic rabbits. The mechanisms may be related with the down-regulation of the iNOS and SR-B1 mRNA expressions.