摘要
目的分析滨蒿内酯(scoparone,Scop)对动脉粥样硬化(atherosclerosis,AS)大鼠Toll样受体4/核转录因子κB(TLR4/NF-κB)的影响。方法将72只SD大鼠随机分为对照组,模型组,Scop高、中、低剂量组[100mg/(kg·d),50mg/(kg·d),25mg/(kg·d)]和辛伐他汀组[2.5mg/(kg·d)],每组12只。除对照组外各组大鼠制成AS模型。各组大鼠使用对应剂量药物连续灌胃4周。比较各组大鼠治疗前后的体重;检测各组大鼠血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、胆固醇(TC)和甘油三酯(TG)水平,ELISA检测炎症因子白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP)、氧化应激因子超氧化物歧化酶(SOD)、丙二醛(MDA)和氧化修饰低密度脂蛋白(ox-LDL)水平;Western Blot测定主动脉组织中TLR4、NF-κB p65蛋白的表达;采用HE染色观察各组大鼠主动脉组织结构情况。结果与对照组比较,模型组大鼠主动脉内膜厚度、内膜/中膜比值、血脂、炎症因子和氧化应激水平、TLR4和NF-κB p65蛋白表达水平均升高(均P<0.05);与模型组比较,Scop组和辛伐他汀组大鼠主动脉内膜厚度和内膜/中膜比值下降(P<0.05),TG、TC、LDL-C、IL-6、TNF-α、hs-CRP、MDA和ox-LDL水平均下降(均P<0.05),HDL-C水平和SOD活性均升高(均P<0.05),TLR4、NF-κB p65的蛋白表达水平均下调(均P<0.05),HE染色显示主动脉的病理变化明显减轻,且随着Scop剂量的增加,其作用逐渐增强。结论 Scop可能通过抑制TLR4/NF-κB信号通路,降低炎症因子和氧化应激水平,延缓AS的形成。
Objective To analyze the effects of scoparone(Scop) on Toll-like receptor 4/nuclear transcription factors κB(TLR4/NF-κB) in atherosclerosis(AS) rats.Methods Seventy two SD rats were randomly divided into control group,model group,high-dose,medium-dose and low-dose Scop groups [100 mg/(kg·d),50 mg/(kg·d),25 mg/(kg·d)],and simvastatin group [2.5 mg/(kg·d)],12 cases in each group.Except control group,rats were made into AS models in the other groups.The rats in administration groups were given the corresponding dose of drugs for 4-week intragastric administration.The weight in each group was compared.The levels of serum high-density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),cholesterol(TC) and triglyceride(TG) in each group were detected.The levels of inflammatory factors(interleukin 6(IL-6),tumor necrosis factor α(TNF-α),hypersensitive c-reactive protein(hs-CRP))and oxidative stress factors(superoxide dismutase(SOD),malondialdehyde(MDA),oxidized modified low density lipoprotein(ox-LDL)) were detected by ELISA.The expression of TLR4 and NF-κB p65 proteins in aortic tissues was detected by Western Blot.The aortic tissues were observed by HE staining.Results Compared with control group,aortic intima thickness,intima/media thickness,levels of serum lipids,inflammatory factors and oxidative stress,and expression levels of TLR4 and NF-κB p65 protein were increased in modelgroup(P<0.05).Compared with model group,aortic intima thickness and intima/media thickness were decreased(P<0.05),levels of TG,TC,LDL-C,IL-6,TNF-α,hs-CRP,MDA and ox-LDL were decreased(P<0.05),HDL-C level and SOD activity were increased(P<0.05),and expression levels of TLR4 and NF-κB p65 protein were down-regulated in Scop group and simvastatin group(P<0.05).HE staining showed that pathological changes of aorta were significantly reduced.With increase of Scop dose,its roles were gradually increased(P<0.05).Conclusion Scop may reduce levels of inflammatory factors and oxidative stress,delay AS formation by inhibiting TLR4/NF-κB signaling pathway.
作者
何薇
程欢
谭罗超
He Wei;Cheng Huan;Tan Luochao(Department of Critical Care Medic ine,Three Gorges Hospital Affiliated to Chongqing University,Wanzhou 404100,China)
出处
《中国煤炭工业医学杂志》
2020年第6期561-567,共7页
Chinese Journal of Coal Industry Medicine
基金
重庆市自然科学基金资助项目(编号:cstc2018jcyjAX0468)。
作者简介
通讯作者:程欢。
