芳香新塔花总黄酮对ApoE^(-/-)小鼠主动脉TLR4/NF-κB表达及炎症水平的影响  

Effects of Total Flavonoids from Ziziphora clinopodioides Lam. on the Expression of TLR4/NF-κB and the Level of Inflammation in the Aorta of ApoE^(-/-) Mice

作　　者：马晓宇 钊浩然 乔会林 张选明 Ma Xiaoyu;Zhao Haoran;Qiao Huili;Zhang Xuanming(Pharmacy School of Shihezi University,Shihezi 832000;The First Affiliated Hospital of Shihezi University School of Medicine,Shihezi 832008)

机构地区：[1]石河子大学药学院,石河子832000 [2]石河子大学医学院第一附属医院,石河子832008

出　　处：《中药药理与临床》2022年第4期91-95,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81960853);国家中医药管理局青年岐黄学者支持项目[国中医药人教函(2020)218]。

摘　　要：目的:观察芳香新塔花总黄酮对载脂蛋白E基因敲除(ApoE^(-/-))小鼠动脉粥样硬化(AS)斑块及炎症反应的影响及其机制研究。方法:50只健康雄性ApoE小鼠给予高脂饲料,以构建AS模型,随机分成5组并灌胃给药:模型对照组、阿托伐他汀3 mg/kg组、芳香新塔花总黄酮25、50、100 mg/kg组;10只同周龄同性别的健康C57BL/6J小鼠设为正常对照组给予普通饲料,灌胃给予等体积生理盐水。在第12 w末解剖小鼠,取出血清和主动脉血管,经苏木精-伊红(HE)染色观察小鼠主动脉粥样硬化病变;油红O染色观察小鼠主动脉内壁斑块面积;全自动生化仪检测小鼠血清中血脂总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)含量;酶联免疫吸附法(ELISA)检测血清中肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、IL-6含量;Western Blot检测主动脉Toll-样受体4(TLR4)、核转录因子-κB(NF-κB)蛋白变化。结果:与正常对照组比较,模型对照组小鼠血清TC、TG、LDL-C、TNF-α、IL-1β、IL-6含量显著升高,HDL-C含量显著降低(P<0.01);主动脉中TLR4、NF-κB蛋白表达明显上调(P<0.05或P<0.01);与模型对照组比较,芳香新塔花总黄酮50、100 mg/kg组小鼠血清TC、TG、LDL-C、TNF-α、IL-1β、IL-6含量显著降低,HDL-C含量显著升高,主动脉TLR4、NF-κB蛋白表达明显下调(P<0.05或P<0.01)。芳香新塔花总黄酮各剂量组泡沫细胞浸润和内膜下组织斑块明显减少。结论:芳香新塔花总黄酮对ApoE小鼠的AS具有较好的治疗作用,其机制与抑制炎症及TLR4/NF-κB通路有关。Objective:To observe the effects of total flavonoids from Ziziphora clinopodioides Lam. on the atherosclerotic(AS) plaques and inflammatory response in apolipoprotein E knockout(ApoE^(-/-)) mice and explore the underlying mechanism. Methods:Fifty healthy male ApoEmice were given a high-fat diet to establish an AS model and then randomly assigned into five groups: a model group, an atorvastatin(3 mg/kg) group, and high-, medium-, and low-dose(100, 50, and 25 mg/kg, respectively) groups of total flavonoids from Z. clinopodioides. Ten healthy C57 BL/6 J mice of the same age and sex were set as the blank control group and given ordinary feed and administrated with the same volume of normal saline. At the end of the 12 th week, the mice were dissected for the sampling of the serum and aortic blood vessels. The aortic atherosclerotic lesions of the mice were observed via hematoxylin-eosin(HE) staining and the plaque area of the inner wall of the mouse aorta via oil red O staining. An automatic biochemical analyzer was used to measure the serum levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C) in mice. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of tumor necrosis factor-alpha(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) in serum. Western blotting was employed to determine the protein levels of Toll-like receptor 4(TLR4) and nuclear transcription factor-κB(NF-κB) in the aorta. Results:Compared with the blank control group, the modeling of AS elevated the serum levels of TC, TG, LDL-C, TNF-α, IL-1β, and IL-6, lowered the serum level of HDL-C, and up-regulated the protein levels of TLR4 and NF-κB in the aorta(P<0.05 or P<0.01). Compared with the model group, 50 and 100 mg/kg total flavonoids from Z. clinopodioides lowered the levels of TC, TG, LDL-C, TNF-α, IL-1β, and IL-6 in serum, increased the level of HDL-C in serum, and down-regulated the protein levels of TLR4 and NF-κB in

关 键 词：芳香新塔花总黄酮 动脉粥样硬化 炎症因子 核转录因子-ΚB Toll-样受体4 

分 类 号：R285.5[医药卫生—中药学]