| 王翅遥,高严格,张晓东,康晓军,陈蕊蕊.葛根素延缓动脉粥样硬化进展的机制研究[J].,2020,(16):3022-3027 |
| 葛根素延缓动脉粥样硬化进展的机制研究 |
| Study on the Mechanism of Puerarin in Preventing the Progression of Atherosclerosis |
| 投稿时间：2020-03-03 修订日期：2020-03-28 |
| DOI：10.13241/j.cnki.pmb.2020.16.005 |
| 中文关键词: 葛根素 动脉粥样硬化 Sirt3 凋亡 巨噬细胞 |
| 英文关键词: Puerarin Atherosclerosis Sirt3 Apoptosis Macrophages |
| 基金项目:国家自然科学基金青年项目（81800346）；陕西省自然科学基础研究计划-一般项目（2019JQ-422，808081369018） |
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| 中文摘要: |
| 摘要 目的：明确葛根素（Pur）对小鼠动脉粥样硬化斑块稳定性的治疗作用及其潜在机制。方法：用高脂饮食喂养成年小鼠诱导动脉粥样硬化模型，将小鼠分为Con组，ApoE-/-组，ApoE-/-+ Pur组。采用HE染色分别检测各组小鼠中动脉粥样硬化斑块面积，免疫荧光染色检测斑块中MMP2的阳性区域面积。用50 μg/mL ox-LDL干预巨噬细胞诱导动脉粥样硬化细胞模型，并用Ad-sh-Sirt3干扰Sirt3表达，将细胞分为Con组、ox-LDL组、ox-LDL+Pur组、ox-LDL+Pur+Ad-sh-Sirt3组。Western-blot检测Sirt3表达含量，TUNEL法检测巨噬细胞凋亡。结果：动物水平，与Con组相比，ApoE-/-组小鼠出现了显著的动脉粥样硬化斑块，ApoE-/-组小鼠MMP2阳性区域面积显著高于Con组（P<0.05）；Pur处理后，ApoE-/-+ Pur组动脉粥样硬化斑块面积明显低于ApoE-/-组（P<0.05），MMP2的阳性区域面积显著低于ApoE-/-组（P<0.05）。细胞水平，Western结果显示，与对照组相比，ox-LDL组Sirt3表达量显著降低（P<0.05），ox-LDL+Pur组Sirt3表达水平显著高于ox-LDL组（P<0.05）。相比于Con组，ox-LDL组巨噬细胞凋亡水平显著升高（P<0.05）；给予Pur处理后，相比于单纯ox-LDL组，ox-LDL+Pur组巨噬细胞的凋亡水平显著降低（P<0.05）。Ad-sh-Sirt3处理消除了葛根素对于巨噬细胞凋亡的抑制作用（P<0.05）。结论：外源性Pur可能通过激活Sirt3表达，进一步降低巨噬细胞凋亡水平，减少巨噬细胞的浸润，增加动脉粥样硬化斑块稳定性。 |
| 英文摘要: |
| ABSTRACT Objective: To clarify the therapeutic effect of Puerarin (Pur) on stability of atherosclerotic plaques and its underlying mechanism. Methods: High-fat-diet was used to induce atherosclerosis model, the mice were divided into Con group, ApoE-/- group and ApoE-/-+Pur group. The plaque area was measured by HE staining, the positive area of MMP2 in plaques were detected by immunofluorescence staining. In vitro, 50 μg/mL ox-LDL was used to simulate atherosclerosis and Ad-sh-Sirt3 was used to inhibit Sirt3 expression. Cells were divided into Con group, ox-LDL group, ox-LDL + Pur group, ox-LDL + Pur + Ad-sh-Sirt3 group. Western-blot was used to detect the expression of Sirt3. The level of apoptosis in macrophages was detected by TUNEL assay. Results: Compared with the Con group, the mice in the ApoE-/- group showed significant atherosclerotic plaques, the positive area of MMP2 in ApoE-/- mice were significantly higher than Con group(P<0.05). The plaque area and the positive area of MMP2 in ApoE-/- mice were significantly higher than ApoE-/-+Pur group (P<0.05). In cell level, western blot showed that compared with Con group, the expression of Sirt3 in ox-LDL group was significantly reduced (P<0.05). Treatment with Pur significantly increased the expression of Sirt3 compared with ox-LDL group (P<0.05). Furthermore, compared with the Con group, the level of macrophage apoptosis with ox-LDL administration was significantly increased (P<0.05), and Pur administration significantly reduced the apoptosis levels of cells compared with ox-LDL group (P<0.05). Conclusion: Pur effectively reduced the level of macrophage apoptosis and the infiltration of macrophages, increased the stability of atherosclerotic plaques by activating Sirt3 expression. |
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