田蓟苷对动脉粥样硬化模型小鼠的改善作用及机制研究  

Improvement effects of tilianin on atherosclerosis model mice and its mechanism study

作　　者：曹文疆[1] 信盼 赵云丽 袁勇[1] 郭新红[1] 马晓莉 黄川生[1] 文志萍 王新春[1] 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)

机构地区：[1]石河子大学医学院第一附属医院药剂科,新疆石河子832008

出　　处：《中国药房》2022年第1期19-25,共7页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81860747,No.81960766)。

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-β_(1)/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。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-αin 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-αin 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 inflammation and regulate lipid metabolism to inhibit the formation of AS.

关 键 词：田蓟苷 动脉粥样硬化 转化生长因子β_(1)/Smads信号通路 炎症反应 脂质代谢 

分 类 号：R285[医药卫生—中药学]