阿托伐他汀对ApoE基因敲除小鼠血管外膜成纤维细胞表型的影响

发布时间：2018-03-25 14:21

本文选题：ApoE-/-小鼠　切入点：动脉粥样硬化　出处：《中国病理生理杂志》2016年09期

【摘要】：目的:观察载脂蛋白E基因敲除(ApoE~(-/-))小鼠动脉粥样硬化斑块形成过程中血管外膜α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β1(TGF-β1)的表达变化,同时探讨阿托伐他汀抗动脉粥样硬化的作用机制。方法:选择40只6周龄雄性ApoE~(-/-)小鼠随机分为模型组和阿托伐他汀干预组,给予高脂饲料喂养。阿托伐他汀干预组给予阿托伐他汀(20 mg·kg~(-1)·d~(-1))灌胃,模型组给予等量生理盐水灌胃。20只同龄C57BL/6小鼠给予普通饲料喂养作为正常对照组。各组小鼠喂养至10、15周龄,在各个时点处死动物,取升主动脉制备连续切片,通过Movat染色进行形态学观察,测量并计算血管外膜厚度及斑块相对面积;天狼星红染色检测胶原的表达;免疫组织化学染色检测不同时点血管外膜α-SMA及TGF-β1的表达变化。用实时荧光定量PCR检测胸主动脉外膜中TGF-β1 mRNA的表达水平,通过Western blot法检测主动脉外膜中TGF-β1蛋白的表达。结果:与模型组相比,阿托伐他汀干预组的斑块相对面积明显减小,血管外膜厚度及胶原合成明显下降;免疫组化结果显示15周龄模型组血管外膜α-SMA及TGF-β1的表达高于10周龄模型组;与模型组相比,阿托伐他汀干预组血管外膜α-SMA及TGF-β1的表达明显下降。各时点模型组的TGF-β1 mRNA和蛋白的表达明显高于对照组,给药干预后TGF-β1 mRNA和蛋白的表达明显降低。15周龄模型组血管外膜TGF-β1 mRNA和蛋白的表达高于10周龄模型组。结论:阿托伐他汀可能通过下调TGF-β1的表达调控血管外膜成纤维细胞表型的改变,进而延缓ApoE~(-/-)小鼠动脉粥样硬化的进程。
[Abstract]:Aim: to observe the expression of 伪 -SMA- and TGF- 尾 1 in adventitia during atherosclerotic plaque formation in apolipoprotein E knockout (ApoE) knockout mice. Methods: forty 6-week-old male ApoE-/ -r-/-mice were randomly divided into two groups: model group and Atto vastatin intervention group. The Atto vastatin intervention group was given Atto vastatin (20 mg kg / kg) DX)) and the model group was given the same amount of normal saline. 20 C57BL/6 mice of the same age were fed with normal diet as the normal control group. The mice in each group were fed to 10 ~ 15 weeks of age. At each time point, the animals were killed and the ascending aorta was taken to prepare serial sections. The thickness of adventitia and the relative area of plaque were measured and calculated by Movat staining, and the expression of collagen was detected by Sirius red staining. The expression of 伪 -SMA and TGF- 尾 1 in the adventitia of thoracic aorta was detected by immunohistochemical staining. The expression of TGF- 尾 1 mRNA in thoracic aortic adventitia was detected by real-time fluorescence quantitative PCR. The expression of TGF- 尾 1 protein in the aortic adventitia was detected by Western blot. Results: compared with the model group, the relative area of plaque, the thickness of adventitia and collagen synthesis in the Atto vastatin intervention group were significantly decreased. The expression of 伪 -SMA and TGF- 尾 1 in vascular adventitia of 15-week-old model group was higher than that of 10-week-old model group. The expression of 伪 -SMA and TGF- 尾 1 in the vascular adventitia of the Atto vastatin intervention group was significantly decreased, and the expression of TGF- 尾 1 mRNA and protein in the model group was significantly higher than that in the control group. The expression of TGF- 尾 1 mRNA and protein in vascular adventitia of 15 weeks old model group was significantly lower than that of 10 week old model group. Conclusion: Atto vastatin may regulate vascular adventitial fibrogenesis by down-regulation of TGF- 尾 1 expression. Changes in the phenotypes of vascular cells, This in turn delays the progression of atherosclerosis in ApoEG-r-r-mice.
【作者单位】：滨州医学院病理生理学教研室;滨州医学院附属医院;
【基金】：国家自然科学基金资助项目(No.81401625)
【分类号】：R543.5

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