基于TLR4/NF-κB信号通路探究心脉康改善兔动脉粥样硬化的机制

Study on Mechanism of the Improvement Effects of Xinmaikang on Atherosclerosis in Rabbits Based on TLR4/NF-κB Signaling Pathway

目的:探究心脉康改善兔动脉粥样硬化(AS)的机制。方法:将50只雄性新西兰兔随机分为假手术组、模型组、辛伐他汀组[阳性对照,2.60 mg/(kg·d)]和心脉康低、高剂量组[0.21、0.84 g/(kg·d)],每组10只。假手术组兔给予普通饲料喂养,只分离结扎股动脉但不损伤腹主动脉内皮;其余各组兔均给予高脂饲料喂养并行腹主动脉内膜球囊损伤术以复制AS模型。术后10周,假手术组和模型组兔均灌胃生理盐水,各药物组兔灌胃相应药液(溶剂均为生理盐水),给药体积为100 mL,每天给药1次,连续12周。末次给药后,观察各组兔腹主动脉及内壁的病理变化,检测血清中三酰甘油(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)以及白细胞介素6(IL-6)、IL-1β含量,检测腹主动脉组织中Toll样受体4(TLR4)、核因子κB p65(NF-κB p65)含量及其蛋白表达水平。结果:与假手术组比较,模型组兔腹主动脉管腔内膜富含脂质,管壁厚度和斑块面积明显增加,可见明显的血管内皮损伤;血清中TG、TC、LDL-C、IL-6、IL-1β含量和腹主动脉组织中TLR4、NF-κB p65含量及其蛋白表达水平均显著升高,HDL-C含量显著降低(P<0.05或P<0.01)。与模型组比较,心脉康高剂量组和辛伐他汀组兔腹主动脉病变减轻,且内壁未见明显损伤,其TG、TC、LDL-C、IL-6、IL-1β含量以及心脉康低剂量组NF-κB p65含量和TLR4、NF-κB p65蛋白表达水平均显著改善(P<0.05或P<0.01)。结论:心脉康可改善兔AS,其机制可能与下调TLR4、NF-κB p65表达,抑制炎症反应有关。

OBJECTIVE:To explore the mechanism of Xinmaikang improving atherosclerosis(AS)in rabbits.METHODS:A total of 50 male Zealand rabbits were randomly divided into sham operation group,model group,simvastatin group[positive control,2.60 mg/(kg·d)]and Xinmaikang low-dose and high-dose groups[0.21,0.84 g/(kg·d)],with 10 rabbits in each group.Rabbits in sham operation group were fed with ordinary diet,and only femoral artery was separated and ligated,and abdominal aortic endothelium was not strained;the other groups were given high-fat diet and received abdominal aortic intimal balloon injury to induce AS model.Ten weeks after operation,sham operation group and model group were given intragastric administration of normal saline,and administration groups were given corresponding drug solution intragastrically(normal saline as solvent)with the volume of 100 mL,once a day,for consecutive 12 weeks.After last administration,the pathological changes of abdominal aorta and inner wall in rabbits were observed in each group.The serum contents of triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),interleukin-6(IL-6)and IL-1βwere detected,and the contents and protein expression of Toll-like receptor 4(TLR4)and nuclear factor-κB p65(NF-κB p65)in abdominal aortic tissue were determined.RESULTS:Compared with sham operation group,the intima of abdominal aorta in model group was rich in lipids,the thickness of vessel wall and plaque area were increased obviously,and there was obvious vascular endothelial injury.The contents of TG,TC,LDL-C,IL-6 and IL-1βin serum,the contents and protein expression of TLR4 and NF-κB p65 in abdominal aorta tissue were significantly increased,while the content of HDL-C was decreased significantly(P<0.05 or P<0.01).Compared with model group,the lesion of rabbit abdominal aorta were alleviated,and no obvious damage was found on the inner wall.The contents of TG,TC,LDL-C,IL-6,IL-1βof Xinmaikang high-dose group and simvastatin group as well as the content of NF-κB p65 and protein expression of TLR4 and NF-κB p65 were improved significantly(P<0.05 or P<0.01).CONCLUSIONS:Xinmaikang can improve AS in rabbits,and its mechanism may be assicated with inhibiting the expression of TLR4,NF-κB p65 and inhibiting inflammatory response.