槲皮素对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块的消退作用
|
摘要
目的:研究槲皮素对载脂蛋白E基因敲除(apo E~(-/-))小鼠动脉粥样硬化(As)斑块的消退作用及其可能机制。方法:将12周龄雌性apo E~(-/-)小鼠以高脂饮食喂养8周后,更换为普食喂养并随机分为对照组和槲皮素组,每组9只,以0. 5%的羧甲基纤维素钠(CMC-Na)作为溶媒,槲皮素组采用100 mg·kg~(-1)·d~(-1)槲皮素灌胃9周,对照组给予相同体积溶媒灌胃。分别在高脂喂养前后及普食合并灌胃结束时禁食采血,检测血脂水平及单核细胞趋化因子(MCP-1)水平,小鼠安乐死后取主动脉进行油红O染色。同时,槲皮素作用于apo E~(-/-)小鼠原代腹腔巨噬细胞,检测炎症因子及清道夫受体CD36的表达水平。结果:与对照组比较,槲皮素可显著降低小鼠血浆总胆固醇(TC)、三酰甘油(TG)水平及MCP-1含量,并减少主动脉斑块面积(P<0. 05)。同时槲皮素明显降低脂蛋白残粒刺激下巨噬细胞白介素6(IL-6)和MCP-1的mRNA水平,同时下调CD36蛋白水平(P <0. 05)。结论:槲皮素可通过抑制炎症反应,降低血脂水平,发挥消退As斑块的作用。
Objective: To investigate the regressive effect of quercetin on the atherosclerotic( As) lesions in apolipoprotein E gene knockout( apo E~(-/-)) mice and its potential mechanism. Methods: Twelve-week-old female apo E~(-/-)mice were aggravated hyperlipidemia after fed with Western diet for 8 weeks,and then fed with chow diet and randomly divided into two groups,named as the control group and quercetin group with 9 mice in each. Quercetin group was orally given 100 mg·kg~(-1)·d~(-1) quercetin for 9 weeks using0. 5% sodium carboxymethyl cellulose( CMC-Na) as the solvent,and the control group was given the same volume of solvent. The levels of blood lipids were measured using fasting blood treated with or without Western diet,and serum monocyte chemotactic factor 1( MCP-1) was determined using enzyme linked immunosorbent assay( ELISA). The extent of atherosclerosis was examined using Oil Red O-stained aortas after the mice were euthanized. Quercetin acted on apo E~(-/-)mice primary peritoneal macrophages,and the inflammatory factors and the expression level of scavenger receptor CD36 were detected. Results: Plasma TC,TG and MCP-1 levels in quercetin treated mice were significantly decreased when compared with those in the control group( P < 0. 05). Moreover,atherosclerotic lesions of aorta in quercetin group were lowered by nearly 30% of those in the control mice( P < 0. 05). At the same time,quercetin significantly reduced the levels of interleukin-6( IL-6) and MCP-1 in macrophages stimulated by lipoprotein residues,and downregulated the level of CD36 protein( P < 0. 05). Conclusion: Quercetin can play a role in removing As plaque by inhibiting inflammation and lowering blood lipid level.
Objective: To investigate the regressive effect of quercetin on the atherosclerotic( As) lesions in apolipoprotein E gene knockout( apo E~(-/-)) mice and its potential mechanism. Methods: Twelve-week-old female apo E~(-/-)mice were aggravated hyperlipidemia after fed with Western diet for 8 weeks,and then fed with chow diet and randomly divided into two groups,named as the control group and quercetin group with 9 mice in each. Quercetin group was orally given 100 mg·kg~(-1)·d~(-1) quercetin for 9 weeks using0. 5% sodium carboxymethyl cellulose( CMC-Na) as the solvent,and the control group was given the same volume of solvent. The levels of blood lipids were measured using fasting blood treated with or without Western diet,and serum monocyte chemotactic factor 1( MCP-1) was determined using enzyme linked immunosorbent assay( ELISA). The extent of atherosclerosis was examined using Oil Red O-stained aortas after the mice were euthanized. Quercetin acted on apo E~(-/-)mice primary peritoneal macrophages,and the inflammatory factors and the expression level of scavenger receptor CD36 were detected. Results: Plasma TC,TG and MCP-1 levels in quercetin treated mice were significantly decreased when compared with those in the control group( P < 0. 05). Moreover,atherosclerotic lesions of aorta in quercetin group were lowered by nearly 30% of those in the control mice( P < 0. 05). At the same time,quercetin significantly reduced the levels of interleukin-6( IL-6) and MCP-1 in macrophages stimulated by lipoprotein residues,and downregulated the level of CD36 protein( P < 0. 05). Conclusion: Quercetin can play a role in removing As plaque by inhibiting inflammation and lowering blood lipid level.
引文
1 Tietge UJ.Hyperlipidemia and cardiovascular disease:inflammation,dyslipidemia,and atherosclerosis[J].Curr Opin Lipidol,2014,25(1):94-95
2 Back M,Hansson GK.Anti-inflammatory therapies for atherosclerosis[J].Nat Rev Cardiol,2015,12(4):199-211
3汪元元,肖宏.酶解-溶剂联合提取洋葱中槲皮素的研究[J].中国药师,2012,15(9):1234-1238
4 Li Y,Yao J,Han C,et al.Quercetin,Inflammation and Immunity[J].Nutrients,2016,8(3):167
5 Lu XL,Zhao CH,Yao XL,et al.Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway[J].Biomed Pharmacother,2017,85:658-671
6 Xiao L,Liu L,Guo X,et al.Quercetin attenuates high fat diet-induced atherosclerosis in apolipoprotein E knockout mice:A critical role of NADPH oxidase[J].Food Chem Toxicol,2017,105:22-33
7 Emini Veseli B,Perrotta P,De Meyer GRA,et al.Animal models of atherosclerosis[J].Eur J Pharmacol,2017,816:3-13
8 Du F,Gesang Q,Cao J,et al.Isoliquiritigenin attenuates atherogenesis in apolipoprotein E-deficient mice[J].Int J Mol Sci,2016,17(11):E1932
9 Zhou C,Cao J,Shang L,et al.Reduced paraoxonase 1 activity as a marker for severe coronary artery disease[J].Dis Markers,2013,35:97-103
10 Linden F,Domschke G,Erbel C,et al.Inflammatory therapeutic targets in coronary atherosclerosis-from molecular biology to clinical application[J].Front Physiol,2014,5:455
11 Lin J,Kakkar V,Lu X.Impact of MCP-1 in atherosclerosis[J].Curr Pharm Des,2014,20(28):4580-458
12 Cui Y,Hou P,Li F,et al.Quercetin improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet[J].Lipids Health Dis,2017,16(1):9
13 Garelnabi M,Mahini H,Wilson T.Quercetin intake with exercise modulates lipoprotein metabolism and reduces atherosclerosis plaque formation[J].J Int Soc Sports Nutr,2014,11:22
14 Xue F,Nie X,Shi J,et al.Quercetin inhibits LPS-induced inflammation and ox-LDL-induced lipid deposition[J].Front Pharmacol,2017,8:40
15 Park YM.CD36,a scavenger receptor implicated in atherosclerosis[J].Exp Mol Med,2014,46:e99
16 Ren K,Jiang T,Zhao GJ.Quercetin induces the selective uptake of HDL-cholesterol via promoting SR-BI expression and the activation of the PPARγ/LXRαpathway[J].Food Funct,2018,9(1):624-635
2 Back M,Hansson GK.Anti-inflammatory therapies for atherosclerosis[J].Nat Rev Cardiol,2015,12(4):199-211
3汪元元,肖宏.酶解-溶剂联合提取洋葱中槲皮素的研究[J].中国药师,2012,15(9):1234-1238
4 Li Y,Yao J,Han C,et al.Quercetin,Inflammation and Immunity[J].Nutrients,2016,8(3):167
5 Lu XL,Zhao CH,Yao XL,et al.Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway[J].Biomed Pharmacother,2017,85:658-671
6 Xiao L,Liu L,Guo X,et al.Quercetin attenuates high fat diet-induced atherosclerosis in apolipoprotein E knockout mice:A critical role of NADPH oxidase[J].Food Chem Toxicol,2017,105:22-33
7 Emini Veseli B,Perrotta P,De Meyer GRA,et al.Animal models of atherosclerosis[J].Eur J Pharmacol,2017,816:3-13
8 Du F,Gesang Q,Cao J,et al.Isoliquiritigenin attenuates atherogenesis in apolipoprotein E-deficient mice[J].Int J Mol Sci,2016,17(11):E1932
9 Zhou C,Cao J,Shang L,et al.Reduced paraoxonase 1 activity as a marker for severe coronary artery disease[J].Dis Markers,2013,35:97-103
10 Linden F,Domschke G,Erbel C,et al.Inflammatory therapeutic targets in coronary atherosclerosis-from molecular biology to clinical application[J].Front Physiol,2014,5:455
11 Lin J,Kakkar V,Lu X.Impact of MCP-1 in atherosclerosis[J].Curr Pharm Des,2014,20(28):4580-458
12 Cui Y,Hou P,Li F,et al.Quercetin improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet[J].Lipids Health Dis,2017,16(1):9
13 Garelnabi M,Mahini H,Wilson T.Quercetin intake with exercise modulates lipoprotein metabolism and reduces atherosclerosis plaque formation[J].J Int Soc Sports Nutr,2014,11:22
14 Xue F,Nie X,Shi J,et al.Quercetin inhibits LPS-induced inflammation and ox-LDL-induced lipid deposition[J].Front Pharmacol,2017,8:40
15 Park YM.CD36,a scavenger receptor implicated in atherosclerosis[J].Exp Mol Med,2014,46:e99
16 Ren K,Jiang T,Zhao GJ.Quercetin induces the selective uptake of HDL-cholesterol via promoting SR-BI expression and the activation of the PPARγ/LXRαpathway[J].Food Funct,2018,9(1):624-635