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田蓟苷对动脉粥样硬化模型小鼠的改善作用及机制研究
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| 篇名： | 田蓟苷对动脉粥样硬化模型小鼠的改善作用及机制研究 |
| TITLE： | Improvement effects of tilianin on atherosclerosis model mice and its mechanism study |
| 摘要： | 目的 研究田蓟苷对动脉粥样硬化（AS）模型小鼠的改善作用及可能机制。方法以8只C57BL/6J小鼠作为正常组；将40只载脂蛋白E基因敲除（ApoE－/－）小鼠随机分为模型组，田蓟苷低、中、高剂量组[2.1、3.5、7.0mg/（kg·d）]和辛伐他汀组[阳性对照药物，3.5mg/（kg·d）]，每组8只。正常组小鼠饲以普通饲料，其余各组小鼠饲以高脂饲料建立AS模型。同时，正常组和模型组小鼠灌胃生理盐水，各给药组小鼠灌胃相应药液，每天1次，连续12周。测定小鼠血浆中总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、氧化低密度脂蛋白（Ox-LDL）、白细胞介素1β（IL-1β）、IL-6、单核细胞趋化蛋白1（MCP-1）、肿瘤坏死因子α（TNF-α）水平；观察小鼠主动脉病理形态学变化；测定小鼠主动脉中细胞间黏附分子1（ICAM-1）、血管细胞间黏附分子1（VCAM-1）和增殖细胞核抗原（PCNA）的阳性率；测定小鼠主动脉中基质金属蛋白酶2（MMP-2）、MMP-9、转化生长因子（TGF-β1）、Smad2、Smad3mRNA的表达水平以及TGF-β1、Smad2/3、磷酸化Smad2/3（p-Smad2/3）蛋白的表达水平。结果与正常组比较，模型组小鼠血浆中TC、TG、LDL-C、Ox-LDL、IL-1β、IL-6、MCP-1、TNF-α水平均显著升高（P＜0.01），HDL-C水平显著降低（P＜0.01）；主动脉有脂质斑块生成，且斑块面积较大并致使管腔严重狭窄；主动脉中MMP-2、MMP-9、TGF-β1、Smad2和Smad3mRNA的表达水平，ICAM-1、VCAM-1、PCNA蛋白表达阳性率以及TGF-β1、Smad2/3、p-Smad2/3蛋白的表达水平均显著升高（P＜0.01）。与模型组比较，各给药组上述指标水平大部分均显著回调（P＜0.05或P＜0.01）。结论田蓟苷可能是通过抑制TGF-β1/Smads信号通路的激活，进而抑制血管平滑肌细胞增殖、减轻炎症反应、调节脂质代谢来抑制AS的形成。 |
| ABSTRACT： | OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis （AS）model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE－/－ mice were randomly divided into model group ，tilianin low-dose ，medium-dose and high-dose groups [ 2.1，3.5，7.0 mg/（kg·d）] and simvastatin group [positive control drug ，3.5 mg/（kg·d）]，with 8 mice in each group. Normal group was given normal diet ，and other groups were given high-lipid diet to induce AS model. At the same time ，normal group and model group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，once a day ，for 12 consecutive weeks. The levels of TC ，TG， LDL-C，HDL-C，Ox-LDL，IL-1β，IL-6，MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1，VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as protein expressions of TGF-β1，Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ，the plasma levels of TC ，TG，LDL-C，Ox-LDL，IL-1β， IL-6，MCP-1 and TNF-α in model group were increased significantly（P＜0.01），while HDL-C level was significantly reduced （P＜0.01）. Lipid plaques were formed in the aorta ，and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as positive rate of ICAM- 1，VCAM-1，PCNA and protein expression TGF-β1，Smad2/3，and p-Smad 2/3 in the aorta were significantly increased （P＜0.01）. Compared with model group ， most of above indexes of medication groups were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ，reduce ， inflammation and regulate lipid metabolism to inhibit the No.81960766） formation of AS. |
| 期刊： | 2022年第33卷第01期 |
| 作者： | 曹文疆，信盼，赵云丽，袁勇，郭新红，马晓莉，黄川生，文志萍，王新春 |
| AUTHORS： | CAO Wenjiang，XIN Pan， ZHAO Yunli，YUAN Yong，GUO Xinhong，MA Xiaoli，HUANG Chuansheng，WEN Zhiping，WANG Xinchun |
| 关键字： | 田蓟苷；动脉粥样硬化；转化生长因子β1/Smads信号通路；炎症反应；脂质代谢 |
| KEYWORDS： | tilianin；atherosclerosis；TGF-β1/Smads signaling |
| 阅读数： | 283 次 |
| 本月下载数： | 25 次 |
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