二陈汤合桃红四物汤对ApoE~(-/-)动脉粥样硬化小鼠主动脉Nox4/NF-κB/HIF-1α信号通路作用研究
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摘要
目的:观察二陈汤合桃红四物汤对ApoE基因敲除AS小鼠主动脉Nox4/NF-κB/HIF-1α信号通路的干预作用。方法:50只ApoE~(-/-)小鼠随机分成模型组、中药低、中、高剂量组、阳性对照组,10只C57BL/6J小鼠作为空白对照组。模型组和各治疗组给予高脂饲料喂养,空白组给予普通饲料喂养。于第9周开始,中药低、中、高剂量组、阳性对照组分别给予对应药物治疗4周。Western Blot法检测主动脉Nox4、NK-κB p65蛋白表达水平,RT-PCR法检测主动脉VEGF、MMP-9、HIF-1αmRNA表达水平。结果:与空白对照组比较,模型组小鼠主动脉Nox4、NF-κB p65蛋白表达水平和VEGF、MMP-9、HIF1-αmRNA表达水平显著升高(P<0.01);与模型组比较,各治疗组小鼠主动脉Nox4、NF-κB p65蛋白表达水平和VEGF、MMP-9、HIF1-αmRNA表达水平有不同程度改善,以中药中剂量组、中药高剂量组、阳性对照组效果较为明显(P<0.05,P<0.01)。结论:二陈汤合桃红四物汤抗AS的作用机制可能是通过抑制Nox4/NF-κB/HIF-1α信号通路实现的。
Objective: To investigate the effects of Erchen Decoction and Taohong SiWu Decoction on Nox4/NF-κB/HIF-1α signaling pathway in knockout ApoE~(-/-)atherosclerosis mice. Methods: Fifty ApoE~(-/-)mice were randomly divided into model group, low, medium and high dose traditional Chinese medicine groups, and positive control group, ten C57 BL/6 J mice served as a control group. The model group and the treatment group were fed with high fat diet, while the control group was fed with regular diet. At the beginning of the ninth week, the low, medium and high dose groups and the positive control group were treated with corresponding drugs for 4 weeks. The protein expression levels of Nox4αNF-κB p65 in aorta were detected by Western blot method. The mRNA expression levels of VEGF, MMP-9 and HIF1-α were detected by RT-PCR method. Results:Compared with the control group, the protein expression levels of Nox4 and NF-κB p65, and mRNA expression levels of VEGF,MMP-9, HIF1-α in aorta of model group were significantly increased(P<0.01). Compared with model group, the indexes were improved in different degrees after treatment, and the effect was more obvious with high dose group and positive control group(P<0.05, P<0.01). Conclusion: Erchen Decoction and Taohong Siwu Decoction had positive effect on AS may be achieved by inhibiting the Nox4/NF-κB/HIF-1α signaling pathway.
Objective: To investigate the effects of Erchen Decoction and Taohong SiWu Decoction on Nox4/NF-κB/HIF-1α signaling pathway in knockout ApoE~(-/-)atherosclerosis mice. Methods: Fifty ApoE~(-/-)mice were randomly divided into model group, low, medium and high dose traditional Chinese medicine groups, and positive control group, ten C57 BL/6 J mice served as a control group. The model group and the treatment group were fed with high fat diet, while the control group was fed with regular diet. At the beginning of the ninth week, the low, medium and high dose groups and the positive control group were treated with corresponding drugs for 4 weeks. The protein expression levels of Nox4αNF-κB p65 in aorta were detected by Western blot method. The mRNA expression levels of VEGF, MMP-9 and HIF1-α were detected by RT-PCR method. Results:Compared with the control group, the protein expression levels of Nox4 and NF-κB p65, and mRNA expression levels of VEGF,MMP-9, HIF1-α in aorta of model group were significantly increased(P<0.01). Compared with model group, the indexes were improved in different degrees after treatment, and the effect was more obvious with high dose group and positive control group(P<0.05, P<0.01). Conclusion: Erchen Decoction and Taohong Siwu Decoction had positive effect on AS may be achieved by inhibiting the Nox4/NF-κB/HIF-1α signaling pathway.
引文
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[15]朱中生,王海燕,王登峰,等.瑞舒伐他汀对载脂蛋白E基因缺陷小鼠动脉粥样硬化及LOX-1、NF-κB p65表达的影响.解放军医学杂志,2014,29(12):946-949
[16]王建新,沈晓君.丹参酮ⅡA调控NF-κB通路抗动脉粥样硬化实验研究.河南中医,2013,33(5):681-683
[17]王婉秋,孙侃,靳瑾,等.糖尿病性动脉粥样硬化大鼠血浆VEGF及TGF-β1表达水平的改变和辛伐他汀的保护作用.中国动脉硬化杂志,2014,22(9):929-933
[18]翟小亚,郭航远,池菊芳,等.黄酒多酚对LDLR-/-小鼠MMP-2、MMP-9、TIMP-1、TIMP-2表达和动脉粥样硬化斑块的影响.中国动脉硬化杂志,2013,21(12):1069-1074
[2]王俊岩,陈文娜,贾连群,等.二陈汤合桃红四物汤对Apo E基因敲除动脉粥样硬化小鼠作用及机制研究.中国中医基础医学杂志,2018,24(11):1534-1536,1547
[3]张艳,杨关林,于睿,等.动脉粥样硬化中医虚瘀痰毒病因病机实质研究探讨.时珍国医国药,2007,18(6):1513-1514
[4]杨宝元,张洁,史俊玲,等.冠状动脉粥样硬化形成与中医气虚血瘀病机相关性研究.中西医结合心血管病杂志,2009,7(4):385-387
[5]徐达,吴颢昕.从痰瘀互结论治冠心病的研究进展.中华中医药杂志,2018,33(6):2503-2506
[6]谢盈彧,张军平,仲爱芹,等.从痰瘀立论探讨分期治疗颈动脉粥样硬化.中华中医药杂志,2017,32(1):101-104
[7]周平,罗云,邢娜,等.肿瘤坏死因子α介导动脉粥样硬化发生机制的研究进展.世界中医药,2015,10(8):1163-1168
[8]杨季云,张思仲,郭红,等.肿瘤坏死因子α通过激活NF-κB信号通路加快肝细胞周期进程.生物化学与生物物理进展,2007,34(6):604-610
[9]Gerthoffer W T.Mechanisms of Vascular Smooth Muscle Cell Migration.Circulation Research,2007,100(5):607-621
[10]zumi Y,Kim S,Yoshiyama M,et al.Activation of apoptosis signalregulating kinase 1 in injured artery and its critical role in neointimal hyperplasia.Circulation,2003,108(22):2812-2818
[11]白剑,迟戈,张俊,等.肌肽对低氧所致大鼠血管内皮细胞损伤的保护作用.中国应用生理学杂志,2010,26(1):30-32
[12]刘晓燕,张颖,张燕堂.缺氧诱导因子-1α在动脉粥样硬化发病机制中的研究.世界最新医学文摘,2017,17(33):67
[13]李红艳,贺学,李旭光,等.低氧在动脉粥样硬化发生中的研究进展.医学综述,2015,21(20):3683-3685
[14]周桃,夏豪.缺氧诱导因子-1α与动脉粥样硬化易损斑块.心血管病学进展,2007,28(2):243-245
[15]朱中生,王海燕,王登峰,等.瑞舒伐他汀对载脂蛋白E基因缺陷小鼠动脉粥样硬化及LOX-1、NF-κB p65表达的影响.解放军医学杂志,2014,29(12):946-949
[16]王建新,沈晓君.丹参酮ⅡA调控NF-κB通路抗动脉粥样硬化实验研究.河南中医,2013,33(5):681-683
[17]王婉秋,孙侃,靳瑾,等.糖尿病性动脉粥样硬化大鼠血浆VEGF及TGF-β1表达水平的改变和辛伐他汀的保护作用.中国动脉硬化杂志,2014,22(9):929-933
[18]翟小亚,郭航远,池菊芳,等.黄酒多酚对LDLR-/-小鼠MMP-2、MMP-9、TIMP-1、TIMP-2表达和动脉粥样硬化斑块的影响.中国动脉硬化杂志,2013,21(12):1069-1074