调肝导浊汤调节ApoE~(-/-)小鼠ADMA的分泌量干预主动脉血流速度及峰压的实验研究
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摘要
目的:观察调肝导浊方干预后Apo E-/-小鼠血清中e NOS、ADMA含量的变化,以及其对主动脉血流速度和峰压的影响,探讨调肝导浊方抗动脉粥样硬化的机制是否与上述因素有关。方法:将Apo E-/-小鼠随机分成模型组和调肝导浊组,每日给予高脂饮食,C57BL/6L小鼠作为对照组给予普通饮食,经不同方法干预12周后,HE观察各组小鼠主动脉病理变化;VEVO2100小动物超声检测各组小鼠主动脉血流速度及峰压的变化;ELISA法检测血清中e NOS及ADMA的含量变化。结果:HE结果显示对照组主动脉结构完整,未见斑块形成;模型组主动脉组织结构紊乱,内膜明显增厚,斑块形成;调肝导浊组主动脉结构相对完整,内膜轻度增厚。小动物超声结果显示,模型组与对照组相比,血流速度减慢,血管峰压降低,具有统计学差异(P<0.05);相较于模型组,调肝导浊组血流速度增快,血管峰压升高,差异具有显著性(P<0.05)。ELISA结果显示,与对照组相比,模型组e NOS和ADMA含量增高,具有显著性差异(P<0.05);调肝导浊组相较于模型组,ADMA含量降低,差异具有统计学意义(P<0.05),而e NOS含量未见明显变化(P>0.05)。结论:调肝导浊汤抗动脉粥样硬化作用可能与其调节ADMA的含量变化,干预主动脉血流速度与峰压有关。
Objective: To observe the changes of e NOS and ADMA in serum as well as aortic blood flow velocity and peak pressure of ApoE~(-/-)mice after Tiaogan Daozhuo Decoction intervention and discuss the relationship between atherosclerosis and the above factors. Methods: ApoE~(-/-)mice fed with high-fat diet were random Ly divided into model group and Tiaogan Daozhuo Decoction group,meanwhile C57 BL / 6 mice as the control group were given ordinary diet. 12 weeks later,the pathological changes were observed by HE staining. Ultrasonic instrument for animals was used to detect the changes of aortic blood flow velocity and peak pressure and the serum e NOS and ADMA were detected by ELISA in all groups. Results: HE staining showed that the structure of aortic was integrated and there was no plaque formation in control group. But in model group,the structure of aortic was disorder and classical plaque appeared. On the contrary,there was just an intimal hyperplasia in Tiaogan Daozhuo Decoction group. The ultrasound results showed that compared with the control group,the blood flow velocity and peak pressure were lower in the model group( P < 0. 05),but the above factors were higher in Tiaogan Daozhuo Decoction group compared to those of the model group( P < 0. 05). ELISA result showed that the levels of e NOS and ADMA were higher( P < 0. 05) in model group compared with those of the control group. But in Tiaogan Daozhuo Decoction group ADMA was lower( P < 0. 05) while the level of e NOS did not have an obvious difference compared to that of the model group( P > 0. 05). Conclusion: Tiaogan Daozhuo Decoction has an obvious effect to prevent atherosclerosis and the mechanism may be related to adjusting the level of ADMA,aortic blood flow velocity and peak pressure in ApoE~(-/-)mice.
Objective: To observe the changes of e NOS and ADMA in serum as well as aortic blood flow velocity and peak pressure of ApoE~(-/-)mice after Tiaogan Daozhuo Decoction intervention and discuss the relationship between atherosclerosis and the above factors. Methods: ApoE~(-/-)mice fed with high-fat diet were random Ly divided into model group and Tiaogan Daozhuo Decoction group,meanwhile C57 BL / 6 mice as the control group were given ordinary diet. 12 weeks later,the pathological changes were observed by HE staining. Ultrasonic instrument for animals was used to detect the changes of aortic blood flow velocity and peak pressure and the serum e NOS and ADMA were detected by ELISA in all groups. Results: HE staining showed that the structure of aortic was integrated and there was no plaque formation in control group. But in model group,the structure of aortic was disorder and classical plaque appeared. On the contrary,there was just an intimal hyperplasia in Tiaogan Daozhuo Decoction group. The ultrasound results showed that compared with the control group,the blood flow velocity and peak pressure were lower in the model group( P < 0. 05),but the above factors were higher in Tiaogan Daozhuo Decoction group compared to those of the model group( P < 0. 05). ELISA result showed that the levels of e NOS and ADMA were higher( P < 0. 05) in model group compared with those of the control group. But in Tiaogan Daozhuo Decoction group ADMA was lower( P < 0. 05) while the level of e NOS did not have an obvious difference compared to that of the model group( P > 0. 05). Conclusion: Tiaogan Daozhuo Decoction has an obvious effect to prevent atherosclerosis and the mechanism may be related to adjusting the level of ADMA,aortic blood flow velocity and peak pressure in ApoE~(-/-)mice.
引文
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[20]李志华,周俊琴,李海英,等.芪丹煎对动脉粥样硬化家兔内皮素及一氧化氮合酶含量的影响[J].疑难病杂志,2007,6(9):534-536.
[2]Libby P,Ridker P M,Hansson G K.Progress and challenges in translating the biology of atherosclerosis[J].Nature,2011,473(7347):317-325.
[3]张柏丽,陆一竹,范英昌,等.调肝导浊法中药对动脉粥样硬化家兔血载脂蛋白含量及主动脉病变影响的实验研究[J].天津中医学院学报,2001,20(4):30-31.
[4]陆一竹,范英昌,任学军.调肝导浊中药防治家兔动脉粥样硬化病变形成的实验研究[J].中国医药学报,2002,17(9):532-533,576.
[5]张柏丽,陆一竹,范英昌.调肝导浊法中药抗高血脂及动脉粥样硬化的研究[J].辽宁中医杂志,2002,29(8):509-510.
[6]张凯.动脉粥样硬化大血管和微血管病变的干预靶点研究[D].济南:山东大学,2014.
[7]李庆.彩色多普勒超声评估下肢动脉斑块形成所致血流动力学改变的研究[J].实用医技杂志,2008,15(8):959-962.
[8]任华日.外周动脉血流动力学机制的多普勒超声研究[D].西安:第四军医大学,2014.
[9]薛永亮,唐宁,华晓东,等.一氧化氮与动脉粥样硬化[J].中国动脉硬化杂志,2009,17(8):698-701.
[10]王新国,惠汝太.内皮型一氧化氮合酶在冠状动脉粥样硬化性心脏病的作用[J].中国分子心脏病学杂志,2011,11(3):174-178.
[11]Martinez-Ruiz A,Villanreva L,Orduna C,et al.S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities[J].Proc Natl Acad Sci USA,2005,102(24):8525-8530.
[12]薛永亮,唐宁,华晓东,等.一氧化氮与动脉粥样硬化[J].中国动脉硬化杂志,2009,17(8):698-701.
[13]王进,杜波,单爱军.内皮型一氧化氮合酶基因多态性对一氧化氮水平的影响[J].医学综述,2014,20(4):580-583.
[14]Cooke JP.Asymmetrical dimethylarginine:the Uber marker[J].Circulation,2004,109:1813-1818.
[15]Laurent S,Boutouyrie P,Asmar R,et al.Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients[J].Hypertension,2001,37:1236-1241.
[16]Kielstein JT,Zoccali C.Asymmetric dimethylarginine:a cardiovascular risk factor and a uremic toxin coming of age[J].Am J Kidney Dis,2005,46:186-202.
[17]Boger RH,Sydow K,Borlak J,et al.LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells:involvement of S-adenosylmethionine-dependent methyltransferases[J].Circ Res,2000,87:99-105.
[18]Thum T,Tsikas T,Stein S,et al.Suppression of endothelial progenitor cells inhuman coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine[J].J Am Coll Cardiol,2005,46:1693-1701.
[19]李海英,杨晓庆,李海敏,等.芪脂饮对动脉粥样硬化家兔内皮素及一氧化氮合酶含量的影响[J].中华中医药学刊,2007,25(8):1652-1654.
[20]李志华,周俊琴,李海英,等.芪丹煎对动脉粥样硬化家兔内皮素及一氧化氮合酶含量的影响[J].疑难病杂志,2007,6(9):534-536.