虎杖苷通过抑制TGF-β/Smad信号通路改善动脉粥样硬化大鼠动脉粥样硬化斑块和内皮炎症反应  

Polydatin improves atherosclerotic plaque and endothelial inflammation in atherosclerotic rats by inhibiting TGF-β/Smad signaling pathway

作　　者：张志勇[1] 田辉[1] ZHANG Zhiyong;TIAN Hui(Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430014,China)

机构地区：[1]武汉市中医医院,武汉430014

出　　处：《中国免疫学杂志》2024年第6期1228-1233,共6页Chinese Journal of Immunology

基　　金：武汉市医学科研项目(WZ21B05)。

摘　　要：目的:探讨虎杖苷通过抑制转化生长因子β(TGF-β)/Smad信号通路对动脉粥样硬化(AS)大鼠AS斑块和内皮炎症反应的改善作用。方法:将60只大鼠随机分成空白对照组、模型对照组、虎杖苷低、中、高剂量组和阳性对照组,每组10只。正常对照组大鼠用普通饲料喂养,其余各组大鼠采用高脂饲料喂养与维生素D3腹腔注射联合的方法制备AS大鼠模型。虎杖苷低、中、高剂量组大鼠每天灌胃虎杖苷40、80、160 mg/kg,阳性对照组大鼠每天灌胃辛伐他汀5 mg/kg,模型对照组和空白对照组大鼠每天灌胃等量生理盐水。给药结束后,油红O染色观察大鼠主动脉AS斑块形成情况;全自动生化分析仪检测大鼠三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平;酶联免疫吸附法检测大鼠血清中肿瘤坏死因子(TNF)-α、IL-6、IL-8、C反应蛋白(CRP)、单核细胞趋化蛋白1(MCP-1)、同型半胱氨酸(Hcy)、细胞间黏附分子1(ICAM-1)、内皮素-1(ET-1)含量;蛋白免疫印迹法检测大鼠TGF-β1、Smad2/3、p-Smad2/3蛋白表达水平。结果:与空白对照组相比,模型对照组大鼠主动脉内壁出现大量AS斑块,血清中TG、TC、LDL-C水平及TNF-α、IL-6、IL-8、CRP、MCP-1、Hcy、ICAM、ET-1含量明显升高,HDL-C水平明显降低,主动脉组织中TGF-β1蛋白表达、p-Smad2/3/Smad2/3显著升高(P<0.05)。虎杖苷干预后AS大鼠主动脉内壁斑块面积明显减小,血清中TG、TC、LDL-C水平及TNF-α、IL-6、IL-8、CRP、MCP-1、Hcy、ICAM、ET-1含量显著降低,HDL-C水平显著升高,主动脉组织中TGF-β1蛋白表达、p-Smad2/3/Smad2/3明显减小(P<0.05),以上指标变化均呈剂量依赖性(P<0.05)。阳性对照组TC、LDL-C、HDL-C水平与虎杖苷高剂量组无明显差异(P>0.05),其余指标均比虎杖苷高剂量组更低(P<0.05)。结论:虎杖苷通过调节血脂、降低细胞炎症因子的表达,从而减少AS斑块的形成,改�Objective:To investigate the improvement effect of polydatin on atherosclerotic(AS)plaque and endothelial in-flammation in AS rats by inhibiting transforming growth factorβ(TGF-β)/Smad signaling pathway.Methods:Sixty rats were randomly divided into blank control group,model control group,low,medium and high dose polydatin groups and positive control group,with 10 rats in each group.The rats in the normal control group were fed with ordinary feed,and the rats in the other groups were used to prepare AS rat models by feeding with high-fat feed and intraperitoneally injected with vitamin D3.The rats in the low-dose,medium-dose and high-dose polydatin groups were given 40,80 and 160 mg/kg of polydatin by gavage every day,the rats in the positive control group were given 5 mg/kg of simvastatin by gavage every day,and the rats in the model control group and the blank control group were given the same amount of normal saline by gavage every day.After the administration,oil red O staining was used to observe the forma-tion of AS plaque in the rat aorta;automatic biochemical analyzer was used to detect the levels of rat triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C);enzyme-linked immunosor-bent assay was used to detect the contents of tumor necrosis factor(TNF)-α,IL-6,IL-8,C-reactive protein(CRP),monocyte che-moattractant protein 1(MCP-1),homocysteine(Hcy),intercellular adhesion molecule 1(ICAM-1)and endothelin-1(ET-1)in se-rum;Western blot was used to detect the protein expression levels of TGF-β1,Smad2/3 and p-Smad2/3 in rats.Results:Compared with blank control group,a large number of AS plaques appeared on the inner wall of the aorta in the model control group,the levels of TG,TC,LDL-C,TNF-α,IL-6,IL-8,CRP,MCP-1,Hcy,ICAM and ET-1 in the serum were significantly increased,the level of HDL-C was significantly reduced,and the expression of TGF-β1 protein and the of p-Smad2/3/Smad2/3 in aortic tissue were signifi-cantly increased(P<0.05

关 键 词：虎杖苷 TGF-Β/SMAD信号通路 动脉粥样硬化 动脉粥样硬化斑块 内皮炎症 

分 类 号：R285.5[医药卫生—中药学]