黄连素降低ApoE^(-/-)小鼠内脏脂肪素表达

Berberine Down-regulating Visfatin Expression in ApoE Knockout Mice

目的:观察黄连素(Ber)对载脂蛋白E基因敲除(Apo E-/-)小鼠主动脉粥样硬化(AS)病变、内脏脂肪素(visfatin)及炎症因子表达的影响。方法:50只SPF级8周龄雄性Apo E-/-小鼠予高脂饲料喂养随机分为5组:Ber低、中、高剂量组分别ip给予Ber 2.5,5,7.5 mg·kg-1·d-1;辛伐他汀组ig辛伐他汀5 mg·kg-1·d-1;模型组ig等量生理盐水。另设10只相同基因背景和周龄的雄性C57BL/6J小鼠为对照组予普通饲料喂养。16周后测小鼠体重、血清脂质及visfatin,血浆白介素(IL-6)及肿瘤坏死因子-α(TNF-α)水平;HE染色观察小鼠主动脉组织AS斑块面积;免疫组化法测AS斑块内visfatin的表达;Western blotting测小鼠主动脉visfatin蛋白的表达。结果:小鼠体重增加值,血清visfatin,总胆固醇(TG),三酰甘油(TC),低密度脂蛋白胆固醇(LDL-C)水平,血浆IL-6及TNF-α含量,主动脉visfatin蛋白表达方面,模型组均显著高于对照组(P<0.05),各给药组均显著低于模型组(P<0.05);辛伐他汀组,Ber中、高剂量组小鼠主动脉AS斑块面积比显著低于模型组(P<0.05)。结论:Ber可通过降血脂、减小AS斑块面积、降低IL-6及TNF-α含量等发挥抗AS效应,其机制可能与降低visfatin表达有关。

Objective： To study the effect of berberine （Ber） on plaque area quantification, visfatin and inflammatory cytokines expression in ApoE knockout （ApoE-/-） mice. Method： Fifty male 8-week-o｜d ApoE-/- mice were fed with a high fat diet and randomly assigned into five groups： model group, low-dose Bet （2.5 mg·kg^-1·d^-1） group, medium-dose Ber （5 mg·kg^-1·d^-1） group, high-dose Ber （7.5 mg·kg^-1·d^-1） group and simvastatin （5 mg·kg^-1·d^-1） group. Ten C57BL/6J mice fed with a common diet were served as control group. Serum lipids and visfatin, plasma interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） levels were determined after 16 weeks. Atherosclerotic lesions in the aortic root were examined by H＆E staining. Visfatin expression in the aorta and distribution in atherosclerotic plaques were identified by Western blottingand byimmunohistochemistry. Result： The add weight value, serum visfatin, triglyceride （TG）, total cholesterol （TC） and low densty lipoprotein chdesterol （LDL-C）, plasma IL-6 and TNF-α, visfatin expression in the aorta of model group were statistically increased compared with control group and each treatment group （P 〈 0.05 ）. Atherosclerosis plaque lesions in aorta of simvastatin group, high-dose Ber group and medium-dose Ber group were statistically decreased compared with model group （P 〈 0.05）. Conclusion： Ber can inhibit the development of atherosclerosis by reducing serum lipids, atherosclerosis plaque, plasma IL-6 and TNF-α levels in ApoE-/- mice, the mechanism is related to down-regulating visfatin expression.