摘要
目的探究枸杞多糖(LBP)对动脉粥样硬化(AS)小鼠体内脂联素(APN)表达的调控及其调脂抗炎作用机制。方法普通饲料喂养的C57BL/6J小鼠为对照组,采用高胆固醇饲料喂养Apo E-/-小鼠成功建立AS模型,随机分为模型组和3个LBP组(高、中、低剂量分别为100、50、25 mg/kg)。继续喂养4周后,取主动脉血和组织,分别检测血脂、炎症因子、内皮素-1(ET-1)、APN及其受体(Adipo R1)、AMPK通路相关指标的表达;3T3-L1前脂肪细胞经诱导分化后分为对照组、LBP组和LBP+BML-275组,检测各组中三酰甘油(TG)、炎症因子、APN、Adipo R1、AMPK通路相关指标的表达。结果与对照组比较,模型组小鼠出现典型的AS病理变化,TG、总胆固醇(TC)、一氧化氮(NO)、ET-1、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平明显升高,高密度脂蛋白(HDL-C)、APN和Adipo R1、PPARα、AMPKα、p-AMPKα蛋白表达和酰基辅酶A氧化酶(ACO)m RNA表达均明显降低;与模型组比较,LBP组中AS病理变化得到明显改善,TG、TC、NO、ET-1、IL-6和TNF-α的水平降低,HDL-C、APN和Adipo R1、PPAR-α、AMPKα、p-AMPKα蛋白及ACO m RNA表达升高,并且这些变化呈剂量相关性。3T3-L1脂肪细胞中,与对照组比较,LBP组的APN、Adipo R1、PPARα、AMPKα、p-AMPKα和ACO的表达均明显升高,TG、IL-6和TNF-α的水平明显降低;与LBP组比较,LBP+BML-275组TG、IL-6和TNF-α水平明显升高。结论 LBP通过上调APN和Adipo R1表达,激活APN/AMPK通路,发挥调脂抗炎作用,从而减缓小鼠动脉粥样硬化。
Objective To explore the effect of Lycium barbarum polysaccharide （LBP） on adiponectin （APN） expression and the mechanism of lowering blood-lipid and anti-inflammation in atherosclerotic （AS） mice. Methods C57BL/6J mice with normal feed were chosen as control group. Thirty-two ApoE-/- mice with high cholesterol diet were successfully established as AS models, and then the mice were randomly divided into model group and three LBP groups, which were feed with high, medium, and low dose of LBP. After feeding for four weeks, aortic blood and tissues were collected. Blood-lipid, inflammatory factors, endothelin-1 （ET-1）, APN, AdipoR1, and AMPK pathway related protein expression were detected. Differentiated 3T3-L1 cells were divided into control group, LBP group, and LBP ＋ BML-275 group. Triglyceride （TG）, inflammatory factors, APN, AdipoR1, and AMPK pathway related protein expression was investigated. Results In mice, compared with the control group, typical AS pathomorphologic changes were found in aorta and the levels of TG; total cholesterol （TC）, nitric oxide （NO）, ET-1, interleukin-6 （IL-6）, and tumor necrosis factor （TNF-α） in the model group were significantly increased, while the protein expression of HDL-C, APN, AdipoR1, PPARα, AMPKα, and p-AMPK-α and Acyl-CoA oxidase （ACO） mRNA expression was reduced. Compared with the model group, AS pathomorphologic state was obviously improved in aorta and the amount of TG, TC, NO, ET-1, IL-6, and TNF-α in LBP groups were markedly decreased, while the protein expression of HDL-C, APN, AdipoR1, PPARα, AMPKα, p-AMPKα, and ACO mRNA expression was up-regulated. These changes were all in a dose-dependent manner. In differentiated 3T3-L1 fat cells, compared with control group, LBP enhanced the expression of APN, AdipoR1, PPARα, AMPKα, p-AMPKα, and ACO, but decreased the amount of TG, IL-6, and TNF-α. Compared with LBP group, the levels of TG, IL-6 and TNF-α was notably increased in BML-275 group. Conclusion LBP up-regulates the expression of APN and AdipoR1, activates APN/AMPK pathway, plays a role in lowering blood-lipid and anti-inflammation, and thus relieves AS in mice.
作者
呼蕾
董玲
屈蕾
王丽滨
吴雯雯
王海芳
HU Lei DONG Ling QU Lei WANG Li-bin WU Wen-wen WANG Hai-fang(Medical Clinical laboratory, Northwest Women and Children＇s Hospital, Xi＇an 710061, China Shaanxi Provincial Key Laboratory of Infectious and Immunological Diseases, Shaanxi Province People＇s Hospital, Xi＇an 710068, China)
出处
《药物评价研究》
CAS
2017年第3期292-299,共8页
Drug Evaluation Research
基金
国家自然科学基金资助项目(81573823)
关键词
枸杞多糖
脂联素
AMPK通路
动脉粥样硬化
Lycium barbarum polysaccharide
adiponectin
AMPK signaling pathway
atherosclerosis
