米诺环素抗兔动脉粥样硬化作用及机制
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Resistance Effect and Mechanism of Minocycline Against Atherosclerosis in Rabbit
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    摘要:

    目的观察米诺环素对动脉粥样硬化斑块干预治疗后基质金属蛋白酶的分子病理学改变,评价该药对动脉粥样硬化的治疗效果,并分析其作用机制。方法40只新西兰兔,随机取5只设为正常对照组。另35只建立动脉粥样硬化斑块兔模型(经腹主动脉使用兔气囊致动脉去上皮化损伤,并连续用高脂饲料喂养3个月)后,除在实验过程死亡或患病5只兔外,其余随机分4组,即动脉粥样硬化模型组(8只,继续高脂喂养1个月)、普食恢复组(7只,改用常规饲料喂养1个月)、氟伐他汀组[7只,给予氟伐他汀1 mg/(kg.d)连续干预治疗1个月]和米诺环素组[8只,连续给予米诺环素3 mg/(kg.d)治疗1个月]。各组动物分别麻醉后处死并切取腹主动脉,按常规石蜡包埋切片,以M asson染色法观察动脉粥样硬化斑块病理形态学变化,免疫组织化学法检测动脉粥样硬化斑块内炎症细胞及基质金属蛋白酶表达水平,原位杂交Tunel染色法检测细胞凋亡。结果动脉管壁组织经M asson染色观察显示,正常对照组未见异常病理变化,模型组和普食恢复组均呈现典型动脉粥样硬化病变特征,而米诺环素和氟伐他汀两治疗组病变明显减轻,尤以前者改善突出。各组动脉粥样硬化斑块巨噬细胞含量及基质金属蛋白酶3和9的表达水平与病变程度相一致,前三者间在各组动物中的表达水平均呈正相关关系(P<0.001)。斑块内巨噬细胞含量、基质金属蛋白酶3和9的水平在米诺环素组均显著低于模型组和普食恢复组(P<0.05),且在米诺环素组可见平滑肌细胞明显增加。结论米诺环素具有改善动脉粥样硬化病变程度和稳定动脉粥样硬化斑块的作用。

    Abstract:

    Aim To observe the effect of minocycline on atherosclerosis(As) after the treatment of atherosclerosis plaque-intervention with changes in the level of molecular pathology,evaluate drug effects on treatment of As and analyze its mechanism. Methods 5 as normal control group were randomly taken from 40 New Zealand rabbits. 35 rabbits were used as atherosclerotic animal model after balloon-induced arterial injury to the epithelium and use of high-fat diet for 3 months.In addition to death or illness of five rabbits during experiment,remaining 30 rabbits were randomly divided into 4 groups,namely,model group(8 rabbits,high fat diet for 1 month),reconverted normal diet group(7 rabbits,conventional feeding for 1 month),fluvastatin treatment group(7 rabbits,given fluvastatin 1 mg/(kg·d) intervention for 1 month);minocycline treatment group(8 rabbits,given minocycline with a dose on 3 mg/(kg·d)).The animals were sacrificed and the abdominal aorta in each group were cut,paraffin-embedded sections,Masson staining were used to observe the morphological changes of As plaque and inflammatory cells,expression levels of matrix metalloproteinases(MMP) were examined with the immuno-histochemistrical staining,using in situ hybridization-Tunel staining detection of apoptotic cells in As plaque of these animal. Results Histopathology artery wall by Masson staining showed no pathological changes in normal group,model control group and reconverted normal diet group showed the typical features of As lesions,and two groups with treatment of the minocycline and fluvastatin significantly reduce the pathological change,especially the former.In plaque of As of each group,macrophage(RAM-11) and expression levels of matrix metalloproteinase(MMP-3 and MMP-9)had positive correlation (P<0.001).But macrophage content in plaque and MMP expression level in the minocycline treatment and the fluvastatin treatment group were significantly lower compared with the model control group(P<0.05).And smooth muscle cells markedly increased in minocycline group. Conclusion Minocycline can relieve severity of As treatment of diseases and improve the stability of atherosclerotic plaque.

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周军,周丽,曾庆仁.米诺环素抗兔动脉粥样硬化作用及机制[J].中国动脉硬化杂志,2009,17(11):912~916.

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  • 收稿日期:2009-07-06
  • 最后修改日期:2009-10-05
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