芳香新塔花对动脉粥样硬化模型小鼠Tol样受体-4/核因子-κB信号通路的影响  

Ziziphora clinopodioides Lam.Attenuates Atherosclerosis in Mice via Modulating TLR4/NF-κB Signaling Pathway

作　　者：张华 马学宽 王思静 张选明 倪昀 王丽 安冬青 ZHANG Hua;MA Xuekuan;WANG Sijing;ZHANG Xuanming;NI Yun;WANG Li;AN Dongqing(The University Hospital,Xinjiang Medical University,Famous Doctors and Prescriptions and Characteristic Traditional Medical Formulac Laboratory of Xinjiang,Urumqi(830011),Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学校医院新疆名医名方与特色方剂学实验室,新疆维吾尔自治区乌鲁木齐市830011

出　　处：《中国循环杂志》2020年第4期395-400,共6页Chinese Circulation Journal

基　　金：国家自然科学基金(81360528)。

摘　　要：目的:通过研究芳香新塔花(新塔花)对动脉粥样硬化模型载脂蛋白E基因敲除(ApoE-/-)小鼠主动脉Toll样受体-4(TLR4)/核因子-κB(NF-κB)信号通路的影响,探讨新塔花防治动脉粥样硬化的作用机制。方法:选取40只8周龄ApoE-/-小鼠和10只同品系C57小鼠,适应性喂养1周后予以高脂饲料喂养12周。同时在适应性喂养后,将C57小鼠设为空白对照组;ApoE-/-小鼠随机分为模型组、他汀组、新塔花高剂量组和新塔花低剂量组,每组10只。5组小鼠每天灌胃1次,持续12周:空白对照组和模型组均给予蒸馏水(0.4 ml/10 g),他汀组给予阿托伐他汀[3.0 mg/(kg·d)],新塔花高剂量组给予新塔花水提物[1.8 g/(kg·d)],新塔花低剂量组给予新塔花水提物[0.9 g/(kg·d)]。每周记录小鼠体质量变化,并调整用药量。灌胃12周后处理小鼠,采集主动脉。胸主动脉用于苏木精-伊红(HE)染色观察病理变化。腹主动脉采用实时荧光定量PCR(qRT-PCR)检测TLR4、NF-κB的信使RNA(mRNA)相对表达水平;采用蛋白免疫印迹法(Western Blot)检测TLR4、NF-κB蛋白表达水平。结果:qRT-PCR结果显示,与空白对照组比较,模型组TLR4、NF-κB的m RNA相对表达水平升高,差异均有统计学意义(P均<0.05);与模型组比较,他汀组、新塔花高剂量组和低剂量组TLR4、NF-κB的m RNA相对表达水平降低,差异有统计学意义(P均<0.05)。Western Blot结果显示,与空白对照组比较,模型组TLR4、磷酸化NF-κB p65蛋白水平上调,他汀组、新塔花高剂量组和低剂量组TLR4、磷酸化NF-κB p65蛋白水平下调,差异均有统计学意义(P均<0.05)。结论:新塔花具有防治动脉粥样硬化的作用,其机制可能与调控TLR4/NF-κB信号通路、改善内皮功能、抑制炎症反应有关,需进一步深入研究证实。Objectives:To observe the impact of Ziziphora clinopodioides Lam.on Toll-like receptor-4(TLR4)/Nuclear factor-κB(NF-κB)signaling pathway in aorta of apolipoprotein E knockout(ApoE-/-)mice,and to explore the mechanism of Ziziphora clinopodioides Lam.in attenuating atherosclerosis.Methods:Forty 8-week-old ApoE-/-mice and ten C57 mice of the same strain were fed with high-fat diet for 12 weeks to establish atherosclerosis model after 1 week feeding with normal chow,C57 mice served as blank control group(0.4 ml/10 g,distilled water),ApoE-/-mice were randomly divided into following groups(n=10 each):model group[0.4 ml/10 g,distilled water],statin group(3.0 mg/[kg·d],atorvastatin),high dose Ziziphora clinopodioides Lam.group(1.8 g/[kg·d],water extract),low dose of Ziziphora clinopodioides Lam.group(0.9 g/[kg·d],water extract).The weight changes of mice were recorded weekly and the dosage was adjusted accordingly.After 12 weeks,all mice were fasting for 12 h,sacrificed under deep anesthesia,and the aortas were collected under aseptic condition.The thoracic aorta was stained with HE to observe the pathological changes of aorta.The m RNA expression of TLR4 and NF-κB in abdominal aorta was detected by real-time fluorescence quantitative PCR(qRT-PCR),and the protein expression of TLR4 and NF-κB was detected by Western Blot.Results:Atherosclerotic changes were evidenced in model group and reduced in statin group,high dose Ziziphora clinopodioides Lam.group and low dose Ziziphora clinopodioides Lam.group.qRT-PCR results showed that compared with the blank group,the expression of TLR4 and NF-κB in model group was significantly upregulated(all P<0.05);compared with model group,the expression of TLR4 and NF-κB in statin group,high-dose Ziziphora clinopodioides Lam.group were significantly downregulated,expression of NF-κB was significantly downregulated in low dose Ziziphora clinopodioides Lam.group(all P<0.05).Western Blot results showed that compared with blank group,TLR4 and p-NF-κB p65 protein levels in model grou

关 键 词：芳香新塔花 动脉粥样硬化 TOLL样受体-4 核因子-ΚB 信号通路 

分 类 号：R541[医药卫生—心血管疾病]