摘要
目的观察酸枣仁皂苷A(JuA)对高脂肥胖幼鼠血管内皮功能障碍的作用及对Toll样受体(TLR)/核因子κB(NF-κB)炎症信号通路的影响。方法66只21日龄断乳雄性Wistar大鼠,随机分为对照组,模型组,阳性对照(烟酸100 mg·kg-1)组和JuA低、中、高剂量(10、20、40 mg·kg-1)组,每组11只,对照组予以常规饲料,其余各组给予高脂饲料饲养12周造高脂肥胖模型,阳性对照组和JuA各组在高脂饲养同时每日灌胃给予相应剂量药物12周。记录各组大鼠体重及Lee’s指数变化,观察血管内皮细胞的病理改变及凋亡情况,比较血脂水平、血清血管内皮指标水平、血管内皮细胞TLR/NF-κB炎症信号通路mRNA和蛋白的表达。结果与对照组比较,模型组大鼠体重及Lee’s指数均显著增加(P<0.05);总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)显著增高,高密度脂蛋白胆固醇(HDL-C)显著降低(P<0.05);血清一氧化氮(NO)、6-酮-前列腺素F1α(6-keto-PGF1α)、血管内皮生长因子(VEGF)水平显著降低,内皮素1(ET-1)、血栓烷B2(TXB2)、血管性血友病因子(vWF)水平显著增高(P<0.05);胸主动脉内皮细胞凋亡指数(AI)增加(P<0.05);TLR2、TLR4、NF-κB蛋白和mRNA表达显著增加(P<0.05),IκBα表达显著下降(P<0.05)。与模型组比较,JuA各剂量组大鼠体重及Lee’s指数均显著降低(P<0.05);胸主动脉内皮细胞AI减小(P<0.05);TC、TG、LDL-C降低,HDL-C增高(P<0.05);血清NO、6-keto-PGF1α、VEGF增加,ET-1、TXB2、vWF降低(P<0.05);内皮细胞TLR2、TLR4、NF-κB蛋白和mRNA表达水平下调,IκBα上调(P<0.05),且呈剂量依赖性。结论JuA可改善高脂肥胖幼鼠血脂水平,纠正血管内皮功能障碍,其作用可能与下调TLR/NF-κB炎症信号通路有关。
AIM To observe the effects of jujuboside A(JuA)on vascular endothelial dysfunction in high-fat obese young rats and the mechanism of Toll-like receptor(TLR)/nuclear factor-κB(NF-κB)pathway.METHODS A total of 6621-day-old weaned male Wistar rats were randomly divided into control group,model group,positive control(nicotinic acid100 mg·kg-1)group and JuA low,medium and high dose(10,20,40 mg·kg-1)groups using a random number table method,with 11 rats in each group.The control group was given regular feed,and the other groups were given high-fat feed for 12 weeks to create a high-fat obese model.While feeding high-fat feed,the positive control group and JuA groups were given intragastrically the corresponding dose of drugs daily for 12 weeks.The changes in body weight and Lee’s index of rats in each group were recorded,and pathological changes and apoptosis of vascular endothelial cells were observed.The serum lipid levels,serum vascular endothelial index levels,mRNA and protein expression of TLR/NF-κB inflammatory signaling pathway in vascular endothelial cells were compared.RESULTS Compared with the control group,the body weight and Lee’s index of the model group significantly increased(P<0.05),the total cholesterol(TC),triacylglycerol(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly increased,and high-density lipoprotein cholesterol(HDL-C)was significantly reduced(P<0.05),serum nitric oxide(NO),6-keto-prostaglandin F1α(6-keto-PGF1α),and vascular endothelial growth factor(VEGF)levels were significantly reduced(P<0.05),the thoracic aortic endothelial cell apoptosis index(AI)was increased(P<0.05),the levels of endothelin 1(ET-1),thromboxane B2(TXB2),and von Willebrand factor(vWF)were significantly increased(P<0.05),the protein and m RNA expression levels of TLR2,TLR4,and NF-κB were increased(P<0.05),and the expression of IκBαdecreased significantly(P<0.05).Compared with the model group,the body weight and Lee’s index of rats in JuA groups were significantly reduced(P<0.05),endothelial cell AI was decreased(P<0.05),TC,TG,LDL-C were decreased,HDL-C was increased(P<0.05),and serum NO,6-keto-PGF1α,VEGF were increased,ET-1,TXB2 and v WF were decreased(P<0.05),the protein and mRNA expression levels of TLR2,TLR4,NF-κB in endothelial cells were down-regulated,and IκBαwas up-regulated significantly(P<0.05)with a dose-dependent manner.CONCLUSION Ju A can improve blood lipid levels and vascular endothelial dysfunction in high-fat obese young rats,and its effect may be related to downregulation of the TLR/NF-κB inflammatory signaling pathway.
作者
朱建丽
张娜娜
刘小菊
ZHU Jian-li;ZHANG Na-na;LIU Xiao-ju(Department of Pharmacy,Lishui Traditional Chinese Medicine Hospital,Lishui ZHEJIANG 323000,China;Hemodialysis Room,Lishui Traditional Chinese Medicine Hospital,Lishui ZHEJIANG 323000,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2020年第6期374-380,共7页
Chinese Journal of New Drugs and Clinical Remedies
基金
浙江省中医药科学研究基金项目(2019ZA131)。
关键词
酸枣仁皂苷A
肥胖症
膳食
高脂
内皮
血管
炎症
jujuboside A
obesity
diet
high-fat
endothelium
vascular
inflammation
