Page 25 - 《中国药房》2022年1期

田蓟苷对动脉粥样硬化模型小鼠的改善作用及机制研究 Δ

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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（石河子大学医学院第一附属医院
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药剂科，新疆 石河子 832008）

中图分类号 R285 文献标志码 A 文章编号 1001-0408（2022）01-0019-07
DOI 10.6039/j.issn.1001-0408.2022.01.04

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、7.0 mg/（kg·d）]和辛伐他汀组[阳性对照
药物，3.5 mg/（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-β 1 ）、Smad2、Smad3 mRNA的表达水平以及TGF-β 1、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-β 1、Smad2 和
Smad3 mRNA的表达水平，ICAM-1、VCAM-1、PCNA蛋白表达阳性率以及TGF-β 1、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。
关键词 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

Improvement effects of tilianin on atherosclerosis model mice and its mechanism study
CAO Wenjiang，XIN Pan，ZHAO Yunli，YUAN Yong，GUO Xinhong，MA Xiaoli，HUANG Chuansheng，WEN
Zhiping，WANG Xinchun（Dept. of Pharmacy，the First Affiliated Hospital of School of Medicine，Shihezi
University，Xinjiang Shihezi 832008，China）

ABSTRACT OBJECTIVE To study the improvement effects of tilianin on the atherosclerosis（AS）model mice and its potential
mechanism. METHODS Eight C57BL/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-β 1，Smad2 and Smad3 as well as protein expressions of TGF-β 1，Smad2/3 and p-Smad2/3 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-β 1，Smad2 and Smad3 as well as positive rate of ICAM-1，VCAM-1，PCNA and protein
expression TGF-β 1，Smad2/3，and p-Smad2/3 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-β 1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells，reduce
Δ 基 金 项 目 ：国 家 自 然 科 学 基 金 资 助 项 目（No.81860747， inflammation and regulate lipid metabolism to inhibit the
No.81960766） formation of AS.
＊副主任技师，硕士。研究方向：临床检验。E-mail：cwjwxc@ KEYWORDS tilianin；atherosclerosis；TGF-β 1/Smads signaling
163.com pathway；inflammation；lipid metabolism
# 通信作者：主任药师，博士。研究方向：中药民族药新药研究与
开发。E-mail：841175436@qq.com

中国药房 2022年第33卷第1期 China Pharmacy 2022 Vol. 33 No. 1 ·19 ·