黄连素降低ApoE-/-小鼠内脏脂肪素表达

Berberine Down-regulating Visfatin Expression in ApoE Knockout Mice

摘要:

目的: 观察黄连素(Ber)对载脂蛋白E基因敲除(ApoE^-/-)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ApoE^-/-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。

Abstract:

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-old ApoE^-/- mice were fed with a high fat diet and randomly assigned into five groups:model group, low-dose Ber(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 blotting and by immunohistochemistry. 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.