摘要
目的探索香青兰总黄酮对高脂饲料诱导ApoE基因敲除小鼠动脉粥样硬化及TGF-β 1/Smad通路的影响。方法C57BL/6J小鼠为正常对照组,ApoE-/-小鼠随机分为模型组、香青兰总黄酮低、中、高剂量组(21、42、84 mg/kg/d)和辛伐他汀组(3.5 mg/kg/d)。小鼠给药12周后处死,观察主动脉病理形态学变化;采用酶联免疫吸附测定法(ELISA)检测了血清中白介素1β(IL-1β),白介素6(IL-6),肿瘤坏死因子α(TNF-α)及单核细胞趋化因子1(MCP-1)的表达;采用蛋白免疫印迹法(Western Blot)检测了各组主动脉TGF-β1,Smad2/3及P-Smad2/3蛋白的表达情况。结果与模型组相比,各给药组动脉粥样硬化病变减轻,斑块面积与管腔面积比值明显降低(P<0.05或P<0.01),血清中IL-1β、IL-6、TNF-α、MCP-1浓度显著低于模型组(P<0.05或P<0.01)。Western Blot显示各给药组主动脉中TGF-β1、p-Smad2/3以及Smad2/3的蛋白水平显著低于模型组(P<0.01)。结论香青兰总黄酮具有抗动脉粥样硬化的作用,其机制可能与抑制炎症因子表达和干预TGF-β 1/Smad信号通路的转导有关。
Objective To study the effect of Dracocephalum moldavica L.total flavones on the atherosclerosis and TGF-β 1/Smad pathway in high-fat fed ApoE knockout mice. Methods C57 BL/6 J mice were used as normal control group,and ApoE-/-mice were randomly divided into model group,TFDM low,middle,high dose groups(21,42,84 mg/kg/d) and simvastatin group(3.5 mg/kg/d).After 12 weeks of administration,mice were sacrificed to observe the pathological changes of aorta.Serum interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α) and monocyte chemoattractant-1(MCP-1) was detected by enzyme-linked immunosorbent assay(ELISA).Moreover,TGF-β1,Smad2/3 and P-Smad2/3 protein expression in aorta was investigated by Western Blot. Results Compared with the model group,administration groups demonstrated more alleviative atherosclerotic lesions with obvious decrease of the ratio of plaque area to luminal area(P <0.05 or P<0.01).Serum IL-1β,IL-6,TNF-α and MCP-1 levels were significantly lower than those in the model group(P<0.05 or P<0.01).The results of Western Blot showed that the protein levels of TGF-β1,p-Smad2/3 and Smad2/3 in the aortas of each administration group were significantly lower than those in the model group(P<0.01). Conclusion TFDM has anti-atherosclerotic effects,which may be related to the inhibition of inflammatory cytokine expression and intervention in the transduction of TGF-β 1/Smad signaling pathway.
引文
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