白藜芦醇通过Nrf2途径发挥抗冠状动脉粥样硬化及心肌细胞保护作用
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摘要
目的:探讨白藜芦醇通过Nrf2途径发挥抗冠状动脉粥样硬化及心肌细胞保护作用。方法:将50小鼠按随机数字表法分为5组:空白对照组、模型组、白藜芦醇高(150 mg·kg~(-1)·d~(-1))、中(100 mg·kg~(-1)·d~(-1))、低(50 mg·kg~(-1)·d~(-1))剂量组,每组10只。除空白对照组正常喂养外,其余各组均给予高脂饲料喂养。各给药组灌胃给药,体积为0. 4 ml,1次/d,空白对照组和模型组给予等体积生理盐水。每周测量体质量,13周后比较小鼠血脂水平、主动脉及心肌组织改变、Nrf2表达情况等。结果:与空白对照组比较,模型组小鼠从第3周开始体质量较空白对照组显著增加(P <0. 05);血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)水平显著升高,高密度脂蛋白(HDL)水平显著降低(P <0. 05); Nrf2表达差异无统计学意义(P> 0. 05);小鼠动脉内膜斑块面积增多,厚度增大;心肌间隙扩大,细胞排列紊乱,心肌横纹消失。与模型组比较,白藜芦醇高(第3周开始)、中、低(第9周开始)剂量组小鼠的体质量显著降低(P <0. 05);白藜芦醇各剂量组小鼠血清中TC、TG、LDL水平均显著降低,HDL水平和Nrf2表达显著升高(P <0. 05);以上作用均呈剂量依赖性。白藜芦醇组小鼠的病理组织情况与模型组相比得到改善。结论:白藜芦醇能通过Nrf2途径有效发挥抗动脉粥样硬化及心肌保护作用。
Objective: To investigate the anti-coronary atherosclerosis and cardioprotective effect of resveratrol by regulating Nrf2 signal pathway. Methods: Totally 50 mice were randomly divided into 5 groups: the blank control group,the model group,resveratrol high(150 mg·kg~(-1)·d~(-1)),medium(100 mg·kg~(-1)·d~(-1)) and low(50 mg·kg~(-1)·d~(-1)) dosage groups with 10 ones in each.Except for the normal feeding in the blank control group,all the other groups were fed with high-fat diet. All the groups were with intragastric administration,0. 4 ml,once a day,and the blank control group and the model group were given saline with the same volume.The body weight was measured weekly. The blood lipid levels,changes of aortic and myocardial tissue,and Nrf2 expression were tested after 13 weeks. Results: Compared with that in the blank control group,the body weight of mice in the model group increased significantly from the third week( P < 0. 05). The serum levels of TC,TG and LDL in the model group increased significantly,while HDL level decreased significantly( P < 0. 05),and the difference in the Nrf2 expression was not statistically significant( P > 0. 05). The plaque and thickness of area in the model group increased. The myocardial space expanded,the cells were arranged in disorder,and the myocardial striations disappeared. Compared with that in the model group,the body weight of mice in resveratrol at high( from the third week),medium and low( from the ninth week) doses decreased significantly( P < 0. 05),the serum levels of TC,TG and LDL were significantly decreased,and the levels of HDL and Nrf2 were significantly increased( P < 0. 05). All the above effects were dosedependent. The pathological structure of mice in resveratrol groups was improved when compared with that in the model group. Conclusion: Resveratrol can play a role in anti-coronary atherosclerosis and cardioprotective effect through the Nrf2 pathway.
Objective: To investigate the anti-coronary atherosclerosis and cardioprotective effect of resveratrol by regulating Nrf2 signal pathway. Methods: Totally 50 mice were randomly divided into 5 groups: the blank control group,the model group,resveratrol high(150 mg·kg~(-1)·d~(-1)),medium(100 mg·kg~(-1)·d~(-1)) and low(50 mg·kg~(-1)·d~(-1)) dosage groups with 10 ones in each.Except for the normal feeding in the blank control group,all the other groups were fed with high-fat diet. All the groups were with intragastric administration,0. 4 ml,once a day,and the blank control group and the model group were given saline with the same volume.The body weight was measured weekly. The blood lipid levels,changes of aortic and myocardial tissue,and Nrf2 expression were tested after 13 weeks. Results: Compared with that in the blank control group,the body weight of mice in the model group increased significantly from the third week( P < 0. 05). The serum levels of TC,TG and LDL in the model group increased significantly,while HDL level decreased significantly( P < 0. 05),and the difference in the Nrf2 expression was not statistically significant( P > 0. 05). The plaque and thickness of area in the model group increased. The myocardial space expanded,the cells were arranged in disorder,and the myocardial striations disappeared. Compared with that in the model group,the body weight of mice in resveratrol at high( from the third week),medium and low( from the ninth week) doses decreased significantly( P < 0. 05),the serum levels of TC,TG and LDL were significantly decreased,and the levels of HDL and Nrf2 were significantly increased( P < 0. 05). All the above effects were dosedependent. The pathological structure of mice in resveratrol groups was improved when compared with that in the model group. Conclusion: Resveratrol can play a role in anti-coronary atherosclerosis and cardioprotective effect through the Nrf2 pathway.
引文
1杨东鹏,王晓武,董文鹏.白藜芦醇防治冠状动脉粥样硬化作用机制研究进展[J].医学研究生学报,2014,27(12):1323-1327
2王佳,张炯.白藜芦醇对糖尿病大鼠心脏缺血再灌注损伤的保护作用[J].中国动脉硬化杂志,2018,26(2):133-138
3 Radomski MW,Palmer RM,Moncada S.The anti-aggregating properties of vascular endothelium:interactions between prostacyclin and nitric oxide[J].Br J Pharmacol,2012,92(3):639-646
4韩运峰,陈韵岱.冠状动脉粥样硬化病变演变的研究进展[J].中国循证心血管医学杂志,2013,5(6):661-663
5 Weber C,Noels H.Atherosclerosis:current pathogenesis and therapeutic options[J].Nature Medicine,2011,17(11):1410-1422
6黄新宇,刘永林.白藜芦醇激活Nrf2/ARE信号通路降低心肌缺血再灌注损伤大鼠炎症和氧化应激[J].中华中医药学刊,2017,35(6):1516-1520
7杨惠聪,吴阿阳,林洁,等.血浆中CRP、Hcy、LDL、HDL含量与动脉粥样硬化的相关性研究[J].检验医学与临床,2011,8(20):2433-2434
8张颖,孙根义,刘寅,等.冠状动脉粥样硬化与血脂代谢紊乱的因素分析[J].天津医药,2010,38(4):270-272
9 Chang W,Song B,Lim S,et al.Mesenchymal Stem Cells Pretreated with Delivered Hph-1-Hsp70 Protein Are Protected from Hypoxia-Mediated Cell Death and Rescue Heart Functions from Myocardial Injury[J].Stem Cells,2010,27(9):2283-2292
10王恺隽,李铁威,蔺亚晖,等.小而密低密度脂蛋白胆固醇与冠状动脉粥样硬化病变的相关分析[J].中国循环杂志,2017,32(z1):3-4
11 Magyar K,Halmosi R,Palfi A,et al.Cardioprotection by resveratrol:A human clinical trial in patients with stable coronary artery disease[J].Clin Hemorheol Microcirc,2012,50(3):179-87
12郭子源.Nrf2-ARE抗氧化通路及GSK-3β在冠状动脉粥样硬化性心脏病中的作用[D].吉林长春:吉林大学硕士学位论文,2012
13 Stefanson AL,Bakovic M.Dietary regulation of Keap1/Nrf2/AREpathway:focus on plant-derived compounds and trace minerals[J].Nutrients,2014,6(9):3777-3801
14张妍,杜鹃,赵文晓,等.白藜芦醇对大鼠急性心肌缺血的保护作用(英文)[J].中国组织工程研究,2006,10(15):177-179
15刘永,孙海梅,产芳晓,等.白藜芦醇对UVA辐射Ha CaT细胞中Nrf2-Keap1-ARE途径的影响[J].中国组织化学与细胞化学杂志,2009,18(4):474
16廖霞,郑少杰,卢可可,等.植物多酚通过Nrf2/ARE信号通路抗氧化作用研究进展[J].食品科学,2016,37(7):227-232
2王佳,张炯.白藜芦醇对糖尿病大鼠心脏缺血再灌注损伤的保护作用[J].中国动脉硬化杂志,2018,26(2):133-138
3 Radomski MW,Palmer RM,Moncada S.The anti-aggregating properties of vascular endothelium:interactions between prostacyclin and nitric oxide[J].Br J Pharmacol,2012,92(3):639-646
4韩运峰,陈韵岱.冠状动脉粥样硬化病变演变的研究进展[J].中国循证心血管医学杂志,2013,5(6):661-663
5 Weber C,Noels H.Atherosclerosis:current pathogenesis and therapeutic options[J].Nature Medicine,2011,17(11):1410-1422
6黄新宇,刘永林.白藜芦醇激活Nrf2/ARE信号通路降低心肌缺血再灌注损伤大鼠炎症和氧化应激[J].中华中医药学刊,2017,35(6):1516-1520
7杨惠聪,吴阿阳,林洁,等.血浆中CRP、Hcy、LDL、HDL含量与动脉粥样硬化的相关性研究[J].检验医学与临床,2011,8(20):2433-2434
8张颖,孙根义,刘寅,等.冠状动脉粥样硬化与血脂代谢紊乱的因素分析[J].天津医药,2010,38(4):270-272
9 Chang W,Song B,Lim S,et al.Mesenchymal Stem Cells Pretreated with Delivered Hph-1-Hsp70 Protein Are Protected from Hypoxia-Mediated Cell Death and Rescue Heart Functions from Myocardial Injury[J].Stem Cells,2010,27(9):2283-2292
10王恺隽,李铁威,蔺亚晖,等.小而密低密度脂蛋白胆固醇与冠状动脉粥样硬化病变的相关分析[J].中国循环杂志,2017,32(z1):3-4
11 Magyar K,Halmosi R,Palfi A,et al.Cardioprotection by resveratrol:A human clinical trial in patients with stable coronary artery disease[J].Clin Hemorheol Microcirc,2012,50(3):179-87
12郭子源.Nrf2-ARE抗氧化通路及GSK-3β在冠状动脉粥样硬化性心脏病中的作用[D].吉林长春:吉林大学硕士学位论文,2012
13 Stefanson AL,Bakovic M.Dietary regulation of Keap1/Nrf2/AREpathway:focus on plant-derived compounds and trace minerals[J].Nutrients,2014,6(9):3777-3801
14张妍,杜鹃,赵文晓,等.白藜芦醇对大鼠急性心肌缺血的保护作用(英文)[J].中国组织工程研究,2006,10(15):177-179
15刘永,孙海梅,产芳晓,等.白藜芦醇对UVA辐射Ha CaT细胞中Nrf2-Keap1-ARE途径的影响[J].中国组织化学与细胞化学杂志,2009,18(4):474
16廖霞,郑少杰,卢可可,等.植物多酚通过Nrf2/ARE信号通路抗氧化作用研究进展[J].食品科学,2016,37(7):227-232
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