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作 者:罗映[1] 何琦[1] 金磊[1] 周岐新[1] 杨俊霞[1]
机构地区:[1]重庆医科大学药理学教研室重庆市生物化学与生子生物学重点实验室,重庆400016
出 处:《中国生物制品学杂志》2012年第2期193-196,199,共5页Chinese Journal of Biologicals
基 金:国家自然科学基金资助项目(30600812)
摘 要:目的研究小檗碱(Berberine)对动脉粥样硬化家兔模型脂代谢和动脉粥样硬化的影响,并探讨其可能的作用机制。方法采用高脂饲料喂养家兔,建立家兔动脉粥样硬化模型,分别测定小檗碱灌胃前和灌胃后家兔血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;取主动脉,HE染色观察主动脉病理形态学变化;一氧化氮合酶测定试剂盒检测主动脉中诱导型一氧化氮合酶(Inductible nitric oxide synthase,iNOS)活性;实时荧光定量PCR法检测脂肪组织中过氧化物酶体增殖物激活受体γ(Peroxisome proliferator activated receptorγ,PPARγ)基因的水平。结果模型组家兔血清中TC、TG和LDL-C水平与正常对照组相比明显升高(P<0.05);血管内膜明显增厚,可见脂质沉积和泡沫细胞形成;且主动脉中iNOS活性和脂肪组织中PPARγ基因水平显著升高(P<0.05),经小檗碱干预后,家兔血清中TC、TG和LDL-C水平、主动脉iNOS活性和脂肪组织中PPARγ基因的水平较模型组显著降低(P<0.05),主动脉脂质沉积与泡沫细胞的形成减少且均以低剂量小檗碱作用明显。结论小檗碱具有明显的降血脂和抗动脉粥样硬化作用,其作用机制与抑制iNOS的活性和下调PPARγ基因水平有关。Objective To investigate the effect of berberine on lipids metabolism and atherosclerosis of atherosclerotic rabbits as well as the potential mechanism. Methods Rabbit model of atherosclerosis was established by feeding with high fat diet. The serum total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels in sera of model rabbits before and after administration with berberine by gavage were determined. The aortic arteries were observed for pathomorphology by HE staining, and determined for inducible nitric oxide synthase (iNOS) activity by iNOS detection kit. The peroxisome proliferator activated receptor Υ (PPAR',/) mRNA level in adipose tissue was determined by real time fluorescent quantitative PCR method. Results As compared with those of normal rabbits as control, the serum TC, TG and LDL-C levels of model rabbits increased significantly (P 〈 0. 05), while the endangium was thickened, the lipid deposition was observed, the foam cells were formed, and both the iNOS activity in aortic arteries and PPARΥmRNA level in adipose tissue increased significantly (P 〈 0. 05). However, after invention with berberine especially that at a low dosage, the serum TC, TG and LDL-C levels as well as the iNOS activity in aortic arteries and PPARΥmRNA level in adipose tissue decreased significantly (P 〈 0. 05), while the lipid deposition and foam cell formation were relieved. Conclusion Berberine obviously reduced the blood lipid levels and aortic atherosclerosis, of which the mechanisms was associated with the inhibition of iNOS activity and down-regulation of PPAR~ mRNA level.
关 键 词:小檗碱 动脉粥样硬化 脂代谢 诱导型一氧化氮合酶 PPARΓ
分 类 号:Q285.5[生物学—细胞生物学] R543[医药卫生—心血管疾病]
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