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
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