白术水提物对肥胖小鼠血管稳态失衡的影响

Effect of Atractylodes macrocephala water extract on vascular steady-state imbalance in obese mice

目的探讨白术Atractylodes macrocephala水提物对肥胖小鼠血管稳态失衡的改善作用和潜在机制。方法选取40只ICR小鼠,随机分为正常组、模型组、依折麦布片(1 mg/kg)组和白术水提物(4、2 g/kg)组,每组8只,除正常组给予普通饲料外,其余各组每天给予高糖高脂饲料喂养,造模的同时分别ig相应药物,正常组及模型组ig蒸馏水,1次/d,连续11周。给药期间检测小鼠体质量及面温、舌色等中医证候指标;末次给药后,检测血清中一氧化氮(nitric oxide,NO)、内皮素-1(endothelin-1,ET-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及总胆固醇(total cholesterol,TC)水平;取主动脉观察其组织形态学变化,并检测主动脉中白细胞介素-6(interleukin-6,IL-6)、Toll样受体4(Toll-like receptor 4,TLR4)、TNF-α、磷酸化腺苷酸活化蛋白激酶(phosphorylated adenylate-activated protein kinase,p-AMPK)、沉默信息调节因子1(silent information regulator,SIRT1)、过氧化物酶体增殖物活化受体γ共激活因子-1α(peroxisome proliferator-activated receptorγcoactivator-1α,PGC-1α)的蛋白表达。结果白术水提物可显著提高肥胖小鼠旷场水平移动总距离和水平移动速度、排便量、排尿量及面温(P<0.01),增加尾部微循环血流量(P<0.05、0.01),显著降低尿液吸光度、足温(P<0.01),并改善舌色变化(P<0.01),显著降低TC、LDL-C、TNF-α和ET-1水平(P<0.01),升高NO含量(P<0.01),改善主动脉组织结构异常,降低主动脉IL-6、TNF-α、TLR4蛋白表达(P<0.05、0.01),提高p-AMPK、SIRT1、PGC-1α蛋白表达(P<0.05、0.01)。结论白术水提物能够有效缓解倦怠乏力、排便无力、四肢烦热等证候表现,并能改善肥胖引起的主动脉损伤、血管内皮紊乱等血管稳态失衡,其作用机制可能和激活AMPK/SIRT1/PGC-1α通路有关。

Objective To explore the improvement effect and potential mechanism of Atractylodes macrocephala water extract on vascular homeostasis imbalance in obese mice.Methods A total of 40 ICR mice were randomly divided into normal group,model group,Ezetimibe Tablets(1 mg/kg)group and A.macrocephala water extract(4,2 g/kg)groups,with eight mice in each group.Except for the normal group,which was given regular feed,the other groups were given high sugar and high-fat feed every day.While modeling,the corresponding drugs were administered intragastrically separately.The normal group and model group were given distilled water once a day for 11 consecutive weeks.During the administration period,body weight and traditional Chinese medicine syndrome indicators such as facial temperature and tongue color were detected;After the last administration,levels of nitric oxide(NO),endothelin-1(ET-1),tumor necrosis factor-α(TNF-α),low density lipoprotein cholesterol(LDL-C)and total cholesterol(TC)in serum were detected;The aorta was collected and its histological changes was observed;The protein expressions of interleukin-6(IL-6),Toll like receptor 4(TLR4),TNF-α,phosphorylated adenylate activated protein kinase(p-AMPK),silent information regulator 1(SIRT1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)in aorta were detected.Results A.macrocephala water extract significantly increased the total distance and speed of horizontal movement in the open field,defecation volume,urine output,and surface temperature of obese mice(P<0.01),increased tail microcirculation blood flow(P<0.05,0.01),significantly reduced urine absorbance and foot temperature(P<0.01),and improved tongue color changes(P<0.01),significantly reduced levels of TC,LDL-C,TNF-αand ET-1(P<0.01),increased the content of NO(P<0.01),improved abnormal aortic tissue structure,reduced IL-6,TNF-αand TLR4 protein expressions in aorta(P<0.05,0.01),increased p-AMPK,SIRT1 and PGC-1αprotein expressions(P<0.05,0.01).Conclusion A.macrocephala water extract can effectively alleviate symptoms such as fatigue,weakness in defecation,and restlessness in the limbs,and can improve vascular homeostasis imbalances such as aortic injury and endothelial dysfunction caused by obesity.Its mechanism may be related to the activation of AMPK/SIRT1/PGC-1αpathway.