目的 探究枸杞多糖（LBP）對動(dòng)脈粥樣硬化（AS）小鼠體內(nèi)脂聯(lián)素（APN）表達(dá)的調(diào)控及其調(diào)脂抗炎作用機(jī)制。方法 普通飼料喂養(yǎng)的C57BL/6J小鼠為對照組，采用高膽固醇飼料喂養(yǎng)ApoE^-/-小鼠成功建立AS模型，隨機(jī)分為模型組和3個(gè)LBP組（高、中、低劑量分別為100、50、25 mg/kg）。繼續(xù)喂養(yǎng)4周后，取主動(dòng)脈血和組織，分別檢測血脂、炎癥因子、內(nèi)皮素-1（ET-1）、APN及其受體（AdipoR1）、AMPK通路相關(guān)指標(biāo)的表達(dá)；3T3-L1前脂肪細(xì)胞經(jīng)誘導(dǎo)分化后分為對照組、LBP組和LBP+BML-275組，檢測各組中三酰甘油（TG）、炎癥因子、APN、AdipoR1、AMPK通路相關(guān)指標(biāo)的表達(dá)。結(jié)果 與對照組比較，模型組小鼠出現(xiàn)典型的AS病理變化，TG、總膽固醇（TC）、一氧化氮（NO）、ET-1、白介素-6（IL-6）和腫瘤壞死因子-α（TNF-α）的水平明顯升高，高密度脂蛋白（HDL-C）、APN和AdipoR1、PPARα、AMPKα、p-AMPKα蛋白表達(dá)和酰基輔酶A氧化酶（ACO）mRNA表達(dá)均明顯降低；與模型組比較，LBP組中AS病理變化得到明顯改善，TG、TC、NO、ET-1、IL-6和TNF-α的水平降低，HDL-C、APN和AdipoR1、PPAR-α、AMPKα、p-AMPKα蛋白及ACO mRNA表達(dá)升高，并且這些變化呈劑量相關(guān)性。3T3-L1脂肪細(xì)胞中，與對照組比較，LBP組的APN、AdipoR1、PPARα、AMPKα、p-AMPKα和ACO的表達(dá)均明顯升高，TG、IL-6和TNF-α的水平明顯降低；與LBP組比較，LBP+BML-275組TG、IL-6和TNF-α水平明顯升高。結(jié)論 LBP通過上調(diào)APN和AdipoR1表達(dá)，激活A(yù)PN/AMPK通路，發(fā)揮調(diào)脂抗炎作用，從而減緩小鼠動(dòng)脈粥樣硬化。

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.

國家自然科學(xué)基金資助項(xiàng)目（81573823）