杜鹃素对氧化应激诱导血管内皮细胞损伤的保护作用及分子机制研究
|
摘要
目的：杜鹃素是存在于植物中的一种主要二氢黄酮化合物,是中药“满山红”(兴安杜鹃Rhododendron dauricum L.)的主要止咳祛痰活性物质,现代药理学研究表明杜鹃素还具有抗菌、抗炎、免疫抑制及血管平滑肌增值抑制作用。杜鹃素与存在于柑橘类水果中的橙皮素、柚皮素同属二氢黄酮化合物,且具有相似的化学结构特征,但是后者在抗氧化及细胞损伤保护方面研究较多,而杜鹃素抗氧化和细胞保护作用研究目前未见报道。本课题第一部分以具有血管内皮细胞特性的EA.hy926细胞株为研究对象研究杜鹃素对过氧化氢(H202)诱导EA.hy926细胞损伤及凋亡的抑制作用；第二部分主要研究杜鹃素对H202诱导的EA.hy926细胞MAPK信号传导通路的调节作用,以阐明其抑制凋亡的分子信号机制；第三部分初步研究杜鹃素对FeC13诱导大鼠颈动脉血栓形成的抑制作用,以体内研究间接探讨其抑制血管内皮氧化损伤作用。本课题主要通过以上三部分研究来揭示杜鹃素抑制氧化应激诱导的血管内皮细胞损伤作用及其可能的分子机制。
方法：(1)采用MTT法测定H202对EA.hy926细胞活力影响及杜鹃素对H202诱导的EA.hy926细胞活力下降的抑制作用；(2)采用紫外分光光度法测定杜鹃素对H202诱导EA.hy926细胞内丙二醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性的影响；(3)采用流式细胞术测定杜鹃素对H202诱导EA.hy926细胞内活性氧(ROS)水平的影响；(4)采用Annexin V-FITC/PI双染检测杜鹃素对H202诱导EA.hy926细胞凋亡率的影响；(5)采用RT-PCR检测杜鹃素对H202诱导EA.hy926细胞凋亡相关蛋白Bax mRNA、 Bcl-2mRNA的表达影响；(6)通过Western blot检测杜鹃素对H202诱导EA.hy926细胞凋亡相关蛋白Bax、Bcl-2、cleaved caspase-3的表达影响；(7)通过Westernblot结合激光共聚焦检测杜鹃素对H2O2诱导EA.hy926细胞紧密连接蛋白occludin的表达影响；(8)采用Western blot检测杜鹃素对H202诱导EA.hy926细胞丝裂原活化蛋白激酶(MAPK)信号通路的调控作用；(9)采用紫外分光光度法测定杜鹃素对FeC13诱导的大鼠血清丙二醛(MDA)含量及超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性的影响；(10)采用HE染色检测杜鹃素对FeC13诱导的大鼠颈动脉内血栓形成的病理学变化影响。
结果：(1)杜鹃素在浓度小于60μmol/L时对EA.hy926细胞没有检测到细胞毒性作用；(2)杜鹃素在15、30和60μmol/L浓度时具有明显抑制H202诱导的EA.hy926细胞内SOD、GSH-Px活性和细胞活力的降低及MDA和ROS水平的升高(p<0.05),并呈明显剂量关系；(3) Annexin V-FITC/PI双染实验表明杜鹃素在0、15、30和60μmol/L浓度时对H202诱导的EA.hy926细胞凋亡率分别为39.1%、32.35、21.9和15.4%,表明杜鹃素对H202诱导的EA.hy926细胞凋亡具有显著抑制作用(p<0.05);(4) Western blot和RT-PCR检测结果显示杜鹃素在15、30和60μmol/L浓度时具有显著抑制H202诱导EA.hy926细胞内促凋亡蛋白Bax和Bax mRNA表达的升高及抑凋亡蛋白Bcl-2和Bcl-2mRNA表达的降低(p<0.05),且抑制作用呈明显剂量关系;(5) Western blot检测结果表明杜鹃素在15、30和60μmol/L浓度时具有显著抑制H202诱导EA.hy926细胞cleaved caspase-3表达的升高(p<0.05),且抑制作用呈明显剂量关系；(6) Western blot结合激光共聚焦检测结果表明杜鹃素在15、30和60μmol/L浓度时具有显著抑制H202诱导EA.hy926细胞紧密连接蛋白occludin表达的降低(p<0.05),且抑制作用呈明显剂量关系；(7) Western blot检测结果表明杜鹃素对H202诱导的蛋白激酶ERK1/2、p38MAPK、c-Src及蛋白磷酸酶SHP-2磷酸化水平具有明显抑制作用(p<0.05),且抑制作用呈明显剂量关系；(8)大鼠经灌胃给药杜鹃素20、40和80mg/kg,连续14天,FeC13诱导颈主动脉血栓实验结果表明,给药组血清中MDA水平明显低于FeC13模型组,SOD和GSH-Px活性明显高于FeC13模型组(p<0.05),并具有剂量依赖关系;(9)HE染色结果表明高剂量杜鹃素(80mg/kg)具有明显抑制FeCl3诱导的大鼠颈动脉血管内斑块堵塞,表明杜鹃素具有抑制FeC13诱导的血栓形成作用,初步推断可能与其抗氧化应激作用有关。
结论：(1)杜鹃素能够抑制H202诱导的EA.hy926细胞凋亡,其作用机制可能是调节细胞内抗氧化酶SOD和GSH-Px活性、调控Bcl-2家族中Bcl-2和Bax基因及蛋白表达以及调节ERK1/2和p38活性；(2)杜鹃素调控ERK1/2和p38活性与其调控上游c-Src及SHP-2信号有关;(3)初步体内实验表明杜鹃素具有抑制FeCl3诱导大鼠颈动脉血栓形成的作用；(4)初步研究表明杜鹃素具有抗氧化应激及预防细胞损伤作用。
Objective:Farrerol, a major flavanone present in plants, is the main active substance of "Man-shan-hong"(Rhododendron dauricum L.) for antibechic. Modern pharmacological studies indicate that farrerol also has antibacterial, anti-inflammatory, immune suppression and inhibition of vascular smooth muscle cells. Hesperetin and naringenin are main flavanone present in citrus fruits, which display predominantly antioxidative and cytoprotective activities. However, researches on antioxidative and cytoprotective effects of farrerol are very limited. Therefore this paper was designed to research the antioxidative and cytoprotective effects of farrerol. The first part of this paper demonstrated the antioxidative and cytoprotective effects of farrerol on hydrogen peroxide (H2O2)-induced EA.hy926cell lines. The second part of the paper demonstrated the regulation of farrerol on hydrogen peroxide (H2O2)-induced MAPK activation in EA.hy926cell lines. In the third part, the preliminary antiothrombosis of farrerol in vivo were studied on FeCl3-induce carotid artery thrombosis in rats.
Methods:(1) MTT assay was used to detect the inhibition of farrerol on H2O2-induce decrease of EA.hy926cells viability.(2) The intracellular and serum MDA content and SOD, GSH-Px enzymatic activities were detected by UV spectrophotometry to evaluate the regulation of farrerol on H2O2-induced cellular redoxidative level.(3) The regulation of farrerol on H2O2-induced cellular reactive oxygen species (ROS) generation was measured using flow cytometry.(4) PI/Annexin V-FITC double staining assay by flow cytometry was used to detect the effect of farrerol on the cell apoptotic ratio in H2O2-induced EA.hy926cells.(5) The regulation of farrerol on apoptosis-related Bcl-2and Bax genes expressions were obtained by RT-PCR.(6) Western blot method was used to detect the protein expressions of Bcl-2, Bax, cleaved caspase-3, occludin and MAPK activation.(7) Immunofluorescent staining was used to detect the expression of occludin.(8) HE staining was used to detect antithrombosis of farrerol in FeCl3-induce carotid artery thrombosis in rats.
Results:(1) Farrerol at the concentration of less60μmol/L had little cytotoxity on EA.hy926cells.(2) Farrerol (15,30, and60μmol/L) inhibited significantly the decreases of cell viability and cellular enzymatic activities of SOD and GSH-Px and the increase of ROS generation in H2O2-induced EA.hy926cells in a dose-dependent manner (p<0.05).(3) PI/Annexin V-FITC double staining assay demonstrated that farrerol at the concentrations of15,30, and60μmol/L attenuated significantly H2O2-induced EA.hy926cells apoptotic ratio from39.1%to32.35%,21.9%, and15.4%, respectively (p<0.05).(4) Western blot and RT-PCR analysis showed that farrerol of15,30, and60μmol/L inhibited significantly H2O2-induced increase of Bax mRNA and protein expression and the decrease of Bcl-2mRNA and protein expression in a dose-dependent manner (p<0.05).(5) Western blot demonstrated that farrerol showed the obvious regulation on the expression of cleaved caspase-3in H2O2-induced EA.hy926cells in a dose-dependent manner (p<0.05).(6) Western blot and Immuno fluorescent staining demonstrated that farrerol showed the obvious regulation on the expression of occludin in H2O2-induced EA.hy926cells in a dose-dependent manner (p<0.05).(7) Western blot demonstrated that farrerol possessed the obvious regulation on the activiation of protein kinases ERK1/2, p38MAPK and c-Src and protein phosphase SHP-2(p<0.05), which were likely associated with the regulation of apoptosis induced by H2O2in EA.hy926cells.(8) In FeCl3-induced rat carotid arterial thrombosis model, compared with the model, farrerol treatment (20,40, and80mg/kg, i.g.) for14days prevented the the increase of MDA content and the decrease of SOD and GSH-Px activity in Spregue Dawey rats serum in a dose-dependent manner (p<0.05).(9) Hematoxylin and eosin (HE) staining indicated that farrerol with high dose (80mg/kg) prevented the thrombosis in FeCl3-induced rat carotid arterial thrombosis model.
Conclusions:(1) Farrerol had a inhibitive effect on H2O2-induced apoptosis in EA.hy926cells, which is likely associated with the regulation of intracellular MDA and ROS levels, the activities of SOD and GSH-Px, and modulation of the expression of Bax, Bcl-2, cleavedcaspase-3, as well as the phosphorylation of ERX1/2and p38.(2) The regulation of farrerol on the phosphorylation of ERX1/2was likely associated with the modulation on Src and SHP-2.(3) It was demonstrated preliminarily that farrerol displayed antiathrombosis in FeCl3-induced rat carotid arterial thrombosis model.(4) It was indicated preliminarily that farrerol possessed antioxidative and cytoprotective activities.
方法：(1)采用MTT法测定H202对EA.hy926细胞活力影响及杜鹃素对H202诱导的EA.hy926细胞活力下降的抑制作用；(2)采用紫外分光光度法测定杜鹃素对H202诱导EA.hy926细胞内丙二醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性的影响；(3)采用流式细胞术测定杜鹃素对H202诱导EA.hy926细胞内活性氧(ROS)水平的影响；(4)采用Annexin V-FITC/PI双染检测杜鹃素对H202诱导EA.hy926细胞凋亡率的影响；(5)采用RT-PCR检测杜鹃素对H202诱导EA.hy926细胞凋亡相关蛋白Bax mRNA、 Bcl-2mRNA的表达影响；(6)通过Western blot检测杜鹃素对H202诱导EA.hy926细胞凋亡相关蛋白Bax、Bcl-2、cleaved caspase-3的表达影响；(7)通过Westernblot结合激光共聚焦检测杜鹃素对H2O2诱导EA.hy926细胞紧密连接蛋白occludin的表达影响；(8)采用Western blot检测杜鹃素对H202诱导EA.hy926细胞丝裂原活化蛋白激酶(MAPK)信号通路的调控作用；(9)采用紫外分光光度法测定杜鹃素对FeC13诱导的大鼠血清丙二醛(MDA)含量及超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性的影响；(10)采用HE染色检测杜鹃素对FeC13诱导的大鼠颈动脉内血栓形成的病理学变化影响。
结果：(1)杜鹃素在浓度小于60μmol/L时对EA.hy926细胞没有检测到细胞毒性作用；(2)杜鹃素在15、30和60μmol/L浓度时具有明显抑制H202诱导的EA.hy926细胞内SOD、GSH-Px活性和细胞活力的降低及MDA和ROS水平的升高(p<0.05),并呈明显剂量关系；(3) Annexin V-FITC/PI双染实验表明杜鹃素在0、15、30和60μmol/L浓度时对H202诱导的EA.hy926细胞凋亡率分别为39.1%、32.35、21.9和15.4%,表明杜鹃素对H202诱导的EA.hy926细胞凋亡具有显著抑制作用(p<0.05);(4) Western blot和RT-PCR检测结果显示杜鹃素在15、30和60μmol/L浓度时具有显著抑制H202诱导EA.hy926细胞内促凋亡蛋白Bax和Bax mRNA表达的升高及抑凋亡蛋白Bcl-2和Bcl-2mRNA表达的降低(p<0.05),且抑制作用呈明显剂量关系;(5) Western blot检测结果表明杜鹃素在15、30和60μmol/L浓度时具有显著抑制H202诱导EA.hy926细胞cleaved caspase-3表达的升高(p<0.05),且抑制作用呈明显剂量关系；(6) Western blot结合激光共聚焦检测结果表明杜鹃素在15、30和60μmol/L浓度时具有显著抑制H202诱导EA.hy926细胞紧密连接蛋白occludin表达的降低(p<0.05),且抑制作用呈明显剂量关系；(7) Western blot检测结果表明杜鹃素对H202诱导的蛋白激酶ERK1/2、p38MAPK、c-Src及蛋白磷酸酶SHP-2磷酸化水平具有明显抑制作用(p<0.05),且抑制作用呈明显剂量关系；(8)大鼠经灌胃给药杜鹃素20、40和80mg/kg,连续14天,FeC13诱导颈主动脉血栓实验结果表明,给药组血清中MDA水平明显低于FeC13模型组,SOD和GSH-Px活性明显高于FeC13模型组(p<0.05),并具有剂量依赖关系;(9)HE染色结果表明高剂量杜鹃素(80mg/kg)具有明显抑制FeCl3诱导的大鼠颈动脉血管内斑块堵塞,表明杜鹃素具有抑制FeC13诱导的血栓形成作用,初步推断可能与其抗氧化应激作用有关。
结论：(1)杜鹃素能够抑制H202诱导的EA.hy926细胞凋亡,其作用机制可能是调节细胞内抗氧化酶SOD和GSH-Px活性、调控Bcl-2家族中Bcl-2和Bax基因及蛋白表达以及调节ERK1/2和p38活性；(2)杜鹃素调控ERK1/2和p38活性与其调控上游c-Src及SHP-2信号有关;(3)初步体内实验表明杜鹃素具有抑制FeCl3诱导大鼠颈动脉血栓形成的作用；(4)初步研究表明杜鹃素具有抗氧化应激及预防细胞损伤作用。
Objective:Farrerol, a major flavanone present in plants, is the main active substance of "Man-shan-hong"(Rhododendron dauricum L.) for antibechic. Modern pharmacological studies indicate that farrerol also has antibacterial, anti-inflammatory, immune suppression and inhibition of vascular smooth muscle cells. Hesperetin and naringenin are main flavanone present in citrus fruits, which display predominantly antioxidative and cytoprotective activities. However, researches on antioxidative and cytoprotective effects of farrerol are very limited. Therefore this paper was designed to research the antioxidative and cytoprotective effects of farrerol. The first part of this paper demonstrated the antioxidative and cytoprotective effects of farrerol on hydrogen peroxide (H2O2)-induced EA.hy926cell lines. The second part of the paper demonstrated the regulation of farrerol on hydrogen peroxide (H2O2)-induced MAPK activation in EA.hy926cell lines. In the third part, the preliminary antiothrombosis of farrerol in vivo were studied on FeCl3-induce carotid artery thrombosis in rats.
Methods:(1) MTT assay was used to detect the inhibition of farrerol on H2O2-induce decrease of EA.hy926cells viability.(2) The intracellular and serum MDA content and SOD, GSH-Px enzymatic activities were detected by UV spectrophotometry to evaluate the regulation of farrerol on H2O2-induced cellular redoxidative level.(3) The regulation of farrerol on H2O2-induced cellular reactive oxygen species (ROS) generation was measured using flow cytometry.(4) PI/Annexin V-FITC double staining assay by flow cytometry was used to detect the effect of farrerol on the cell apoptotic ratio in H2O2-induced EA.hy926cells.(5) The regulation of farrerol on apoptosis-related Bcl-2and Bax genes expressions were obtained by RT-PCR.(6) Western blot method was used to detect the protein expressions of Bcl-2, Bax, cleaved caspase-3, occludin and MAPK activation.(7) Immunofluorescent staining was used to detect the expression of occludin.(8) HE staining was used to detect antithrombosis of farrerol in FeCl3-induce carotid artery thrombosis in rats.
Results:(1) Farrerol at the concentration of less60μmol/L had little cytotoxity on EA.hy926cells.(2) Farrerol (15,30, and60μmol/L) inhibited significantly the decreases of cell viability and cellular enzymatic activities of SOD and GSH-Px and the increase of ROS generation in H2O2-induced EA.hy926cells in a dose-dependent manner (p<0.05).(3) PI/Annexin V-FITC double staining assay demonstrated that farrerol at the concentrations of15,30, and60μmol/L attenuated significantly H2O2-induced EA.hy926cells apoptotic ratio from39.1%to32.35%,21.9%, and15.4%, respectively (p<0.05).(4) Western blot and RT-PCR analysis showed that farrerol of15,30, and60μmol/L inhibited significantly H2O2-induced increase of Bax mRNA and protein expression and the decrease of Bcl-2mRNA and protein expression in a dose-dependent manner (p<0.05).(5) Western blot demonstrated that farrerol showed the obvious regulation on the expression of cleaved caspase-3in H2O2-induced EA.hy926cells in a dose-dependent manner (p<0.05).(6) Western blot and Immuno fluorescent staining demonstrated that farrerol showed the obvious regulation on the expression of occludin in H2O2-induced EA.hy926cells in a dose-dependent manner (p<0.05).(7) Western blot demonstrated that farrerol possessed the obvious regulation on the activiation of protein kinases ERK1/2, p38MAPK and c-Src and protein phosphase SHP-2(p<0.05), which were likely associated with the regulation of apoptosis induced by H2O2in EA.hy926cells.(8) In FeCl3-induced rat carotid arterial thrombosis model, compared with the model, farrerol treatment (20,40, and80mg/kg, i.g.) for14days prevented the the increase of MDA content and the decrease of SOD and GSH-Px activity in Spregue Dawey rats serum in a dose-dependent manner (p<0.05).(9) Hematoxylin and eosin (HE) staining indicated that farrerol with high dose (80mg/kg) prevented the thrombosis in FeCl3-induced rat carotid arterial thrombosis model.
Conclusions:(1) Farrerol had a inhibitive effect on H2O2-induced apoptosis in EA.hy926cells, which is likely associated with the regulation of intracellular MDA and ROS levels, the activities of SOD and GSH-Px, and modulation of the expression of Bax, Bcl-2, cleavedcaspase-3, as well as the phosphorylation of ERX1/2and p38.(2) The regulation of farrerol on the phosphorylation of ERX1/2was likely associated with the modulation on Src and SHP-2.(3) It was demonstrated preliminarily that farrerol displayed antiathrombosis in FeCl3-induced rat carotid arterial thrombosis model.(4) It was indicated preliminarily that farrerol possessed antioxidative and cytoprotective activities.
引文
[1]Helmut Sies. Biochemistry of oxidative stress. Angew. Chem. Int. Ed. Engl.1986, 25:1058-1071.
[2]Bast A, Goris RJA. Oxidative stress. Biochemistry and human disease. Pharm. Weekbl.1989,11(6):199-206.
[3]Kelvin J.A. Davies. Oxidative stress:the paradox of aerobic life. Biochem. Soc. Symp.1995,61:1-30.
[4]Irwin Fridovich. Superoxide Dismutases. Annu. Rev. Biochem.1975,44: 147-159.
[5]Barry Halliwell. Reactive oxygen species in living systems:source, Biochemistry, and role in human disease. The American Journal of Medicine,1991,91(3C): 14s-22s.
[6]Christopher A. Papaharalambus and Kathy K. Griendling. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med.2007,17:48-54.
[7]Antonio Federico, Elena Cardaioli, Paola Pozza, et al. Mitochondria, oxidative stress and neurodegeneration. Journal of the Neurological Sciences,2012,322(1-2): 254-262.
[8]Chiara Cencioni, Francesco Spallotta, Fabio Martelli, et al. Oxidative stress and epigenetic regulation in ageing and age-related diseases. Int. J. Mol. Sci.,2013,14: 17643-17663
[9]Huige Li, Sven Horke, Ulrich Forstermann. Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacological Sciences,2012,34(6): 313-319.
[10]David Harrison, Kathy K Griendling, Ulf Landmesser, et al. Role of oxidative stress in atherosclerosis. The American Journal of Cardiology,2003,91(3):7-11.
[11]John W Baynes. Role of oxidative stress in development of complications in diabetes. Diabete,1991,40(4):405-412.
[12]A.C. Maritim, R.A. Sanders, J.B. Watkins. Diabetes, oxidative stress, and antioxidants:A review. Journal of Biochemical and Molecular Toxicology,2003, 17(1):24-38.
[13]A.B. Crujeiras, A. Diaz-Lagares, M.C. Carrera, et al. Oxidative stress associated to dysfunctional adipose tissue:a potential link between obesity, type 2 diabetes mellitus and breast cancer. Free Radical Research,2013,47(4):243-256.
[14]James E. Klauning, Lisa M. Kamendulis. The role of oxidative stress in carcinogenesis. Annual Review of Pharmacology and Toxicology,2004,44:239-267.
[15]William R. Markesbery. Oxidative stress hypothesis in Alzheimer's disease. Free Radical Biology and Medicine,1997,23(1):134-147.
[16]Antonio Federico, Elena Cardaioli, Paola Pozza, et al. Mitochondria, oxidative stress and neurodegeneration. Journal of the Neurological Sciences,2012,322(1-2): 254-262.
[17]Huige Li, Sven Horke, Ulrich Forstermann. Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacological Sciences,2013,34(6): 313-319.
[18]H.F. galley, N.R. Webster. Physiology of the endothelium. British Journal of Anaesthesia,2004,93(1):105-113.
[19]Yukihito Higashi, Kensuke Noma, Masao Yoshizumi, Yasuki Kihara. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal,2009,73: 411-418.
[20]Hua Cai, David G. Harrison. Endothelial dysfunction in cardiovascular diseases: the role of oxidative stress. Circulation Research,2000,87:840-844.
[21]Y Higashi, K Noma, M Yoshizumi, Y Kihara. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal,2009,73:411-418.
[22]Paul D. Ray, Bowen Huang, Yoshiaki Tsuji. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling,2012,24: 981-990.
[23]Toren Finkel. Signal transduction by reactive oxygen species. The Journal of Cell Biology,2011,194(1):7-15.
[24]J.T. Hancock, R. Desikan, S.J. Neill. Role of reactive oxygen species in cell signaling pathways. Biochemical and Biomedical Aspects of Oxidative Modification. 2001,29:345-350.
[25]Grag A. Knock, Jeremy P.T. Ward. Redox regulation of protein kinases as a modulator of vascular function. Antioxidants and Redox Signaling,2011,15(6): 1531-1546.
[26]Micheal E. Widlansky, David D. Gutterman. Regulation of endothelial function by mitochondrial reactive oxygen species. Antioxidants and Redox Signaling,2011, 15(6):1517-1530.
[27]N.C. Cook, S. Samman. Flavonoids-chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry,1996,7(2): 66-76.
[28]Elliott Middleton, JR, Chithan Kandaswami, Theoharis C. Theoharides. The effects of plant flavonoids on mammalian cells:implications of inflammation, heart disease, and cancer. Pharmacological Review,2000,52(4):673-751.
[29]Robert J. Williams, Jeremy P.E. Spencer. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radical Biology and Medicine,2012,52(1):35-45.
[30]Noriyoshi Masuoka, Maya Matsuda, Isao Kubo. Characterisation of the antioxidant activity of flavonoids. Food Chemistry,2012,131(2):541-545.
[31]Sam-Long Hwang, Ping-Hsiao Shih, Gow-Chin Yen. Neuroprotective effects of Citrus flavonoids. Journal of Agriculture and Food Chemistry,2012,60(4):877-885.
[32]Wei Dou, jingjing Zhang, Aning Sun, et al. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signaling. British Journal of Nutrition,2013,110(4):599-608.
[33]Changwu Xu, Jing Chen, Jing Zhang, et al. Naringenin inhibits vascular smooth muscle cell function involving reactive oxygen species production modulation and NF-κB activity suppression. Heart,2011,97(21):A83
[34]J. Yang, Q. Li, X.D. Zhou, et al. Naringenin attenuates muscous hypersecretion by modulating reactive oxygen production and inhibiting NF-κB activity via EGFR-PI3K-AKT7ERK MAPKinase signaling in human airway epithelial cells. Molecular and Cellular Biochemistry,2011,351(1-2):29-40.
[35]F.L. Yen, T.H. Wu, L.T. Lin, et al. Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-adminsttered rats with CCl4-induced acute liver failure. Pharmaceutical Research,2009,26(4):893-902.
[36]P.P. Trivedi, S. Kushwaha, D.N. Tripathi, et al. Cardioprotective effects of hesperetin against Doxorubicin-induced oxidative stress and DNA damage in rat. Cardiovascular Toxicology,2011,11(3):215-225.
[37]L. Paris, K. Shagirtha. Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats. Experimental and Toxicologic Pathology,2012, 64(5):513-520.
[38]S.L. Hwang, G.C. Yen. Effect of hesperetin against oxidative stress via ER-and TrkA-mediated action in PC 12 cells. Journal of Agriculture and Food Chemistry, 2011,59(10):5779-5785.
[39]G.D. Zhang, M.Z. Wang, and S.R. Zhang. Studies on the quantitative determination of farrerol in Man-shan-hong(Rhododendron Dauricum T.) leaves. Acta Pharmacol. Sin.1980,15(12):736-740.
[40], J.Z. Qiu, H. Xiang, C. Hu, et al. Subinhibitory concentrations of farrerol reduce a-toxin expression in Staphylococcus aureus. FEMS Microbiol. Lett.2011, 315(2):129-133.
[41]Z.T. Yang, Y.H. Fu, B. Liu, et al. Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus aureus internalization into bovine mammary epithelial cells. Microbial Pathogenesis,2013,65:1-6.
[42]Y. Xiong, S. Zhang, J. Lu, et al. Investigation of effects of farrerol on suppression of murine T lymphocyte activation in vitro and in vivo. International Immunopharmacology,2013,16(2):313-321.
[43]Li, Q.Y., Chen, L., Zhu, Y.H., Zhang, M., Wang, Y.P., and Wang, M.W. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacol. Sin.2011,32(4):433-440.
[1]Elliott Middleton, JR., Chithan Kandaswami, Theoharis C. Theoharides. The effects of plant flavonoids on mammalian cells:implications of inflammation, heart disease, and cancer. Pharmacological Review,2000,52(4):673-751.
[2]Robert J. Williams, Jeremy RE. Spencer. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radical Biology and Medicine,2012,52(1):35-45.
[3]Noriyoshi Masuoka, Maya Matsuda, Isao Kubo. Characterisation of the antioxidant activity of flavonoids. Food Chemistry,2012,131(2):541-545.
[4]G.D. Zhang, M.Z. Wang, and S.R. Zhang. Studies on the quantitative determination of farrerol in Man-shan-hong (Rhododendron Dauricum T.) leaves. Acta Pharmacol. Sin.1980,15(12):736-740.
[5], J.Z. Qiu, H. Xiang, C. Hu, et al. Subinhibitory concentrations of farrerol reduce a-toxin expression in Staphylococcus aureus. FEMS Microbiol. Lett.2011,315(2): 129-133.
[6]Z.T. Yang, Y.H. Fu, B. Liu, et al. Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus aureus intemalization into bovine mammary epithelial cells. Microbial Pathogenesis,2013,65:1-6.
[7]Y. Xiong, S. Zhang, J. Lu, et al. Investigation of effects of farrerol on suppression of murine T lymphocyte activation in vitro and in vivo. International Immunopharmacology,2013,16(2):313-321.
[8]Li, Q.Y., Chen, L., Zhu, Y.H., Zhang, M., Wang, Y.P., and Wang, M.W. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacol. Sin.2011,32(4):433-440.
[9]Hari Prasad Devkota, Masato Watanabe, Takashi Watanabe, and Shoji Yahara. Diplomorphanins A and B:New C-Methyl Flavonoids from Diplomorpha canescens. Chem. Pharm. Bull.,2013,61(2):242-244.
[10]Amer H. Tarawneh, Francisco Leon, Mohamed Ali Ibrahim, Sara Pettaway Christopher R. McCurdy, Stephen J. Cutler. Flavanones from Miconia prasina. Phytochemistry Letters,2014,7:130-132.
[11]Edgell, C.J., McDonald, C.C., and Graham, J.B. Permanent cell line expressing human factor Ⅷ-related antigen established by hybridization. Proc. Natl. Acad. Sci. U.S.A.1983,80(12):3734-3737.
[12]Edgell, C.J.S., Haizlip, J.E., Bagnell, C.R., Packenham, J.P., Harrison, P., Wilbourn, B., et al. Endothelium specific Weibel-Palade bodies in a continuous human cell line, EA.hy926. In Vitro Cell. Dev. Biol.1990,26(12):1167-1172.
[13]Diane, B., Geke, A.P.H., Coby, M., Grietje, M., and Nanno, M. Endothelium in vitro:a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis,2001,4(2):91-102.
[14]Yukihito Higashi, Kensuke Noma, Masao Yoshizumi, Yasuki Kihara. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal,2009,73: 411-418.
[15]Hua Cai, David G. Harrison. Endothelial dysfunction in cardiovascular diseases: the role of oxidative stress. Circulation Research,2000,87:840-844.
[16]Jia, L.Q., Yang, G.L., Ren, L., Chen, W.N., Feng, J.Y., Cao, Y., et al. Tanshinone IIA reduces apoptosis induced by hydrogen peroxide in the human endothelium-derived EA.hy926 cells.2012, J. Ethnopharmacol.143(1):100-108.
[17]Tim Mosmann. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods,1983,65:55-63.
[18]Bast A, Goris RJA. Oxidative stress. Biochemistry and human disease. Pharm. Weekbl.1989,11(6):199-206.
[19]Irwin Fridovich. Superoxide Dismutases. Annu. Rev. Biochem.1975,44: 147-159.
[20]Barry Halliwell. Reactive oxygen species in living systems:source, Biochemistry, and role in human disease. The American Journal of Medicine,1991,91(3C): 14s-22s.
[21]Christopher A. Papaharalambus and Kathy K. Griendling. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med.2007,17:48-54.
[22]Gawel, S., Wardas, M., Niedworok, E., and Wardas, P. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiad. Lek.2004,57(9-10):453-455.
[23]Lykkesfeldt, J. Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin. Chim. Acta,2007,380(1-2):50-58.
[24]Florence Caldefie-Chezet, Stephane Walrand, Christophe Moinard, Arlette Tridon, Jacques Chassagne, Marie-Paule Vasson. Is the neutrophil reactive oxygen species production measured by luminol and lucigenin chemiluminescence intra or extracellular? Comparison with DCFH-DA flow cytometry and cytochrome c reduction. Clinica Chimica Acta,2002,319:9-17.
[25]Rothe G, Valet G. Flow cytometry analysis of respiratory burst activity in phagocytes with hydroethidine and 2'-7'-dichlorofluorescin. J. Leukocyte. Biol.1990, 47:440-448.
[26]Joslyn K. Brunelle and Anthony Letai. Control of mitochondrial apoptosis by the Bcl-2 family. Journal of Cell Science,2009,122:437-441.
[27]Debra T. Chao and Stanley J. Korsmeyer. BCL-2 family:Regulators of Cell Death. Annual Review of Immunology.1998,16:395-419.
[28]Andreas Strasser, Liam O'Connor, and Vishva M. Dixit. Apoptosis signaling. Annu. Rev. Biochem.,2000,69:217-245.
[29]Stefan J. Riedl and Yigong Shi. Molecular mechanisms of caspase regulation during apoptosis. Molecular Cell Biology.2004,5:897-907.
[30]Imawati Budihardjo, Holt Oliver, Michael Lutter, Xu Luo, and Xiaodong Wang. BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS. Annual Review of Cell and Developmental Biology,1999,15: 269-290.
[31]Bazzoni, G, Dejana, E.. Endothelial cell-to-cell junctions:molecular organization and role in vascular homeostasis. Physiol. Rev.2004,84:869-901.
[32]Dejana, E., Corada, M., Lampugnani, M.G.. Endothelial cell-to-cell junctions. FASEB J.1995,9:910-918.
[33]Weis, S.M.. Vascular permeability in cardiovascular disease and cancer. Curr. Opin. Hematol.2008,15:243-249.
[34]Dejana, E., Elisabeth, T.L., Weinstein, B.M.. The control of vascular integrity by endothelial cell junctions:molecular basis and pathological implications. Dev. Cell 2009,16:209-221.
[35]Anderson, J.M., Italie, van C.M.. Tight junctions and the molecular basis for regulation of paracellular permeability. Am. J. Physiol.1995,269:G467-G475.
[36]Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., Tsukita, S.. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J. Cell Biol.1999,147:1351-1363.
[37]Hirase, T, Node, K.. Endothelial dysfunction as a cellular mechanism for vascular failure. Am. J. Physiol. Heart Circ. Physiol.2012,302:H499-H505.
[38]Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., Tsukita, S., Tsukita, S.. Occludin:a novel integral membrane protein localizing at tight junctions. J. Cell Biol.1993,123:1777-1788.
[39]Hirase T., Staddonl J.M., Saitou M., Ando-Akatsuka Y., Itoh M, Furuse M, Fujimoto K., Tsukita S., Rubin L.L., Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci.1997,110,1603-1613.
[40]CHRISTOPHER G. KEVIL, TADAYUKI OSHIMA, BRETT ALEXANDER, LAURA L. COE, and J. STEVEN ALEXANDER. H2O2-mediated permeability:role of MAPK and occludin. Am. J Physiol. Cell Physiol.2000,279:C21-C30.
[41]Balda, M.S., Anderson, J.M.. Two classes of tight junction are revealed by ZO-1 isoforms. Am. J. Physiol.1993,264:C918-C924.
[42]Willott, E., Balda, M.S., Heintzelman, M., Jameson, B, Anderson, J.M.. Localization and differential expression of two isoforms of the tight junction protein ZO-1. Am. J. Physiol. Cell Physiol.1992,262:C1119-C1124.
[43]Somrudee Chuenkitiyanon, Thitima Pengsuparp, and Suree Jianmongkol. Protective Effect of Quercetin on Hydrogen Peroxide-Induced Tight Junction Disruption. International Journal of Toxicology,2010,29(4) 418-424.
[44]Ponio JB-D, El-Ayoubi F, Glacial F, Ganeshamoorthy K, Driancourt C, et al. Instruction of Circulating Endothelial Progenitors In Vitro towards Specialized Blood-Brain Barrier and Arterial Phenotypes. PLoS ONE 2014,9(1):e84179. doi:10.1371/journal.pone.0084179
[1]Y. Zhang and C. Dong. Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci.,2007,64:2771-2789.
[2]Lufen Chang and Michael Karin. Mammalian MAP kinase signalling cascades. Nature,2001,410:37-40.
[3]John M. Kyriakis and Joseph Avruch. MAMMALIAN MAPK SIGNAL TRANSDUCTION PATHWAYS ACTIVATED BY STRESS AND INFLAMMATION:A 10-YEAR UPDATE. Physiol. Rev.,2012,92:689-737.
[4]Xiantao WANG, Jennifer L. MARTINDALE, Yusen LIU and Nikki J. HOLBROOK. The cellular response to oxidative stress:influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem. J., 1998,333:291-300.
[5]Kathryn Z. Guyton, Yusen Liu, Myriam Gorospe, Qingbo Xu, and Nikki J. Holbrook. Activation of Mitogen-activated Protein Kinase by H2O2. THE JOURNAL OF BIOLOGICAL CHEMISTRY,1996,271(8):4138-4142.
[6]Christopher Runchel, Atsushi Matsuzawa, and Hidenori Ichijo. Mitogen-Activated Protein Kinases in Mammalian Oxidative Stress Responses. Antioxidants & Redox Signaling,2011,15(1):205-218.
[7]Eun Su Jeon, Mi Jeong Lee, Sang-Min Sung, and Jae Ho Kim. Sphingosylphosphorylcholine Induces Apoptosis of Endothelial Cells Through Reactive Oxygen Species-Mediated Activation of ERK. Journal of Cellular Biochemistry,2007,100:1536-1547.
[8]Jin-Ran Chen, Lilian I. Plotkin, Jose'Ignacio Aguirre, Li Han, Robert L. Jilka, Stavroula Kousteni, Teresita Bellido, and Stavros C. Manolagas. Transient Versus Sustained Phosphorylation and Nuclear Accumulation of ERKs Underlie Anti-Versus Pro-apoptotic Effects of Estrogens. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2005,280(6):4632-4638.
[9]David Wan-Cheng Li, Jin-Ping Liu, Ying-Wei Mao, Hua Xiang, Juan Wang, Wei-Ya Ma. Zigang Dong, Helen M. Pike, Rhoderick E. Brown, and John C. Reed. Calcium-activated RAF/MEK/ERK Signaling Pathway Mediates p53-dependent Apoptosis and Is Abrogated by aB-Crystallin through Inhibition of RAS Activation. Molecular Biology of the Cell.2005,16:4437-4453.
[10]Shougang Zhuang, Yan Yan, Rebecca A. Daubert, Jiahuai Han, and Rick G. Schnellmann. ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells. Am J Physiol Renal Physiol 2007,292:F440-F447.
[11]JOHN M. KYRIAKIS AND JOSEPH AVRUCH. Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation. PHYSIOLOGICAL REVIEWS,2001,81(2):807-869.
[12]Joseph Schlessinger. Ligand-Induced, Receptor-Mediated Dimerization and Activation of EGF Receptor. Cell,2002,110,669-672.
[13]Mark A. Lemmonl, and Joseph Schlessinger. Cell Signaling by Receptor Tyrosine Kinases. Cell,2010,141:1117-1134.
[14]Sheila M. Thomas, Joan S. Brugge. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Biol.1977,13:513-609.
[15]Hong-Lin Chan, Hsiu-Chuan Chou, MaCarmen Duran, Jana Gruenewald, Michael D.Waterfield, Anne Ridley and John F. Timms. Major Role of Epidermal Growth Factor Receptor and Src Kinases in Promoting Oxidative Stress-dependent Loss of Adhesion and Apoptosis in Epithelial Cells. Journal of Biological Chemistry, 2010,285,4307-4318.
[16]Matthias Stein-Gerlach, Christian Wallasch, Axel Ullrich. SHP-2, SH2-containing protein tyrosine phosphatase-2. The International Journal of Biochemistry & Cell Biology,1998,30:559-66.
[17]Marie Dance. Alexandra Montagner, Jean-Pierre Salles, Armelle Yart, Patrick Raynal. The molecular function of SHP2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway. Cellular Signalling,2008,20:453-459.
[19]CHRISTOPHER G. KEVIL, TADAYUKI OSHIMA, BRETT ALEXANDER, LAURA L. COE, and J. STEVEN ALEXANDER. H:O2-mediated permeability:role of MAPK and occludin. Am. J Physiol. Cell Physiol.2000,279:C21-C30.
[1]S.M. Day, J.L. Reeve, D.D. Myers, W.P. Fay. Murine thrombosis models. Journal of Thrombosis and Haemostasis,2004,92 (3):486-494.
[2]Wei Li, ThomasM.McIntyre, RoyL.Silverstein. Ferric chloride-induced murine carotid arterial injury:A model of redox pathology. Redox Biology,2013,1:50-55.
[3]H.C. Whinna, Overview of murine thrombosis models. Thrombosis Research, 2008,122 (1):S64-S69.
[4]周光兴,高诚,徐平,姚明,谢家骏,胡建华主编, 人类疾病动物模型复制方法学,上海科学技术文献出版社,2008：27。
[5]Lubica Rauova. "Radical" model of thrombosis. Blood,2012,119:1798-1799.
[6]J. Sanz, P.R. Moreno, V. Fuster, The year in atherothrombosis, Journal of the American College of Cardiology 60 (10) (2012) 932-942.
[7]A. ECKLY, B. HECHLER, M. FREUND, M. ZERR, J.-P. CAZENAVE, F LANZA, P. H. MANGIN and C. GACHET. Mechanisms underlying FeCl3-induced arterial thrombosis. Journal of Thrombosis and Haemostasis,2011,9:779-789.
[8]L. Couture, L.P. Richer, M. Mercier, C. Helie, D. Lehoux, S.M. Hossain. Troubleshooting the rabbit ferric chloride-induced arterial model of thrombosis to assess in vivo efficacy of antithrombotic drugs. Journal of Pharmacological and Toxicological Methods,2013,67:91-97.
[9]Hulya Karatas, Sefik Evren Erdener, Yasemin Gursoy-Ozdemir, Gunfer Gurerl, Figen Soylemezoglu, Andrew K Dunn and Turgay Dalkara. Thrombotic distal middle cerebral artery occlusion produced by topical FeCl3 application:a novel model suitable for intravital microscopy and thrombolysis studies. Journal of Cerebral Blood Flow & Metabolism,2011,31:1452-1460.
[10]Lei Shi, Xiu E Feng, Jing Rong Cui, Lian Hua Fang, Guan Hua Du, Qing Shan Li. Synthesis and biological activity of flavanone derivatives. Bioorganic & Medicinal Chemistry Letters,2010,20:5466-5468.
[11]Bo-Nan Zhang, Yun-Long Hou, Bao-Jv Liu, Qing-Mei Liu and Guo-Fen Qiao. The Rhododendron dauricum L. Flavonoids Exert Vasodilation and Myocardial Preservation. Iranian Journal of Pharmaceutical Research.2010,9 (3):303-311
[12]Qun-yi LI, Li CHEN, Yan-hui ZHU, Meng ZHANG, Yi-ping WANG, Ming-wei WANG. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacologica Sinica 2011,32: 433-440.
[13]Zhang, G.W., Wang, L., Fu, P., and Hu, M.M. Mechanism and conformational studies of farrerol binding to bovine serum albumin by spectroscopic methods. Spectrochim. Acta A Mol. Biomol. Spectrosc.2011a,82(1):424-431.
[14]Zhang, G.W., Fu, P., Wang, L., and Hu, M.M. Molecular spectroscopic studies of farrerol interaction with calf thymus DNA. J. Agric. Food Chem.2011b,59(16): 8944-8952.
[15]Zhu, J.F., Li, D.J., Jin, J., and Wu, L.M. Binding analysis of farrerol to lysozyme by spectroscopic methods. Spectrochim. Acta A Mol. Biomol. Spectrosc.2007,68(2): 354-359.
[1]Barry Halliwell. Reactive oxygen species in living systems:source, Biochemistry, and role in human disease. The American Journal of Medicine,1991,91(3C): 14s-22s.
[2]Christopher A. Papaharalambus and Kathy K. Griendling. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med.2007,17:48-54.
[3]Helmut Sies. Biochemistry of oxidative stress. Angew. Chem. Int. Ed. Engl.1986, 25:1058-1071.
[4]Bast A, Goris RJA. Oxidative stress. Biochemistry and human disease. Pharm. Weekbl.1989,11(6):199-206.
[5]Kelvin J.A. Davies. Oxidative stress:the paradox of aerobic life. Biochem. Soc. Symp.1995,61:1-30.
[6]Irwin Fridovich. Superoxide Dismutases. Annu. Rev. Biochem.1975,44: 147-159.
[7]Geiszt M., and Leto T.L.. The Nox family of NAD(P)H oxidases:host defense and beyond. J. Biol. Chem.2004,279:51715-51718.
[8]Miguel Antonio Aon, Brian Alan Stanley, Vidhya Sivakumaran, Jackelyn Melissa Kembro, Brian O'Rourke, Nazareno Paolocci, and Sonia Cortassa. Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission:An experimental-computational study. JGP,2012,139(6):479-185.
[9]Barry Halliwell and Susanna Chirico. Lipid peroxidation:its mechanism, measurement, and significance. Am. J. Clin. Nutr.,1993,57:715s-725s.
[10]John M.C. Gutteridge. Lipid peroxidation and antioxidants as biomarkers of tissue dange. Clin. Chem.,1995,41(12):1819-1829.
[11]ROBERT A. SCHWARTZMAN and JOHN CIDLOWSKI. Apoptosis:The biochemistry and molecular biology of programmed cell death. Endocrine Reviews, 1993,14(2):133-151.
[12]SUSAN ELMORE. Apoptosis:A review of programmed cell death. Toxicologic pathology,2007,35:495-516.
[13]Andreas Strasser, Liam O'Connor, and Vishva M. Dixit. Apoptosis signaling. Annu. Rev. Biochem.,2000,69:217-245.
[14]Imawati Budihardjo, Holt Oliver, Michael Lutter, Xu Luo, and Xiaodong Wang. BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS. Annual Review of Cell and Developmental Biology,1999,15:269-290.
[15]Avi Ashkenazi and Vishva M. Dixit. Death Receptors:Signaling and Modulation. Science,1998,281:1305-1308.
[16]T. Kaufmann, A. Strasser and P.J. Jost. Fas death receptor signalling:roles of Bid and XIAP. Cell Death and Differentiation,2012, (19):42-50.
[17]Dean P. Jones. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol,2008,295:C849-C868.
[18]Lei Cai, Hua Wang, Qin Li, Yunfei Qian, Wenbing Yao. Salidroside inhibits H2O2-induced apoptosis in PC 12 cells by preventing cytochrome c release and inactivating of caspase cascade. Acta Biochimica et Biophysica Sinica,2008,40(9): 796-802.
[19]L. Sun, HY Yan, WY Wong, RA Li, Y Huang, XQ Yao. Role of TRPM2 in H2O2-Induced Cell Apoptosis in Endothelial Cells. PLoS ONE, DOI: 10.1371/journal.pone.0043186.
[20]Shi-Yang Li, Xiao-Guang Wang, Ming-Ming Ma, Yun Liu, Yan-Hua Du, Xiao-Fei Lv, Jia-Guo Zhou, Yong-Bo Tang, Yong-Yuan Guan. Ginsenoside-Rd potentiates apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through the mitochondrial pathway. Apoptosis,2012,17(2):113-120.
[21]查锡良,主编,刘德培,主审,医学分子生物学(供研究生用),人民卫生出版社,2003：382-384.
[22]Y. Zhang and C. Dong. Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci.,2007,64:2771-2789.
[23]Kyriakis JM, Avruch J. Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation:A 10-Year Update. Physiol. Rev.,2012,92: 689-737.
[24]Long Chen, Lei Liu, Jun Yin, Yan Luo, Shile Huang. Hydrogen peroxide-induced neuronal apoptosis is associated with inhibition of protein phosphatase 2A and 5, leading to activation of MAPK pathway. The International Journal of Biochemistry and Cell Biology,2009,41(6):1248-1295.
[25]Zhong-Yan Zhao, Ping Luan, Shi-Xiong Huang, Song-Hua Xiao, Jia Zhao, Bei Zhang, Bei-Bei Gu, Rong-Biao Pi, Jun Liu. Edaravone Protects HT22 Neurons from H2O2-induced Apoptosis by Inhibiting the MAPK Signaling Pathway. CNS Neuroscience and Therapeutics,2013,19(3):163-169.
[26]Xiao Sun, Gui-bo Sun, Min Wang, Jing Xiao, Xiao-bo Sun. Protective effects of cynaroside against H2O2-induced apoptosis in H9c2 cardiomyoblasts. Journal of Cellular Biochemistry,2011,112(8):2019-2029.
[27]Paul D. Ray, Bo-Wen Huang, Yoshiaki Tsuji. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling,2012,24: 981-990.
[28]Chris M. Grant. Regulation of translation by Hydrogen peroxide. Antioxidants and redox signaling,2011,15(1):191-203.
[29]Baoshan Xu, Sujuan Chen, Yan Luo, Zi Chen, Lei Liu, Hongyu Zhou, Wenxing Chen, Tao Shen, Xiuzhen Han, Long Chen, Shile Huang. Calcium Signaling Is Involved in Cadmium-Induced Neuronal Apoptosis via Induction of Reactive Oxygen Species and Activation of MAPK/mTOR Network. PLoS ONE,2011,6(4):e19052. doi:10.1371/journal.pone.0019052
[30]Lorena Pereira, Ana Igea, Begona Canovas, Ignacio Dolado, Angel R. Nebreda. Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis mediated by reactive oxygen species and JNK. EMBO Molecular Medicine,2013, 5(11):1759-1774.
[31]Chia-Jung Hsieh, Po-Lin Kuo, Ying-Chan Hsu, Ya-Fang Huang, Eing-Mei Tsai, Ya-Ling Hsua. Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation. Free Radical Biology and Medicine,2014,67:159-170.
[32]Xu Wanga, Lei Cui, Jacob Joseph, Bingbing Jiang, David Pimental, Diane E. Handy, Ronglih Liao, Joseph Loscalzo. Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. Journal of Molecular and Cellular Cardiology,2012,52(3):753-760.
[33]Tien-Hui Lu, Shan-Yu Hsieh, Cheng-Chien Yen, Hsi-Chin Wu, Kuo-Liang Chen, Dong-Zong Hung, Chun-Hung Chen, Chin-Ching Wu, Yi-Chang Su, Ya-Wen Chen, Shing-Hwa Liu. Chun-Fa Huang. Involvement of oxidative stress-mediated ERK1/2 and p38 activation regulated mitochondria-dependent apoptotic signals in methylmercury-induced neuronal cell injury. Toxicology Letters,2011,204(1):71-80.
[34]John M. Kyriakis, Joseph Avruch. Mammalian MAPK signal transduction pathways activated by stress and inflammation:A 10-year update. Physiological Reviews,2012,92:689-737.
[35]Mervat Ibrahim Khairallah and Lobna Abdel Aal Kassem. Alzheimer's disease: Current status of etiopathogenesis and therapeutic strategies. Pakistan Journal of Biological Sciences,2011,14(4):257-272.
[36]Elena Anahi Bignante, Florencia Heredia, Gerardo Morfini, Alfredo Lorenzo. Amyloid p precursor protein as a molecular target for amyloid β-induced neuronal degeneration in Alzheimer's disease. Neurobiology of Aging,2013,34:2525-2537.
[37]M.T. Lin, M.F. Beal. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature,2006,443:787-795.
[38]D. Pratico. Oxidative stress hypothesis in Alzheimer's disease:a reappraisal. Trends Pharmacol. Sci., 2008,29:609-615.
[39]X. Zhu, H.G. Lee, A.K. Raina, G. Perry, M.A. Smith. The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals, 2002,11:270-281.
[40]B.J. Tabner, O.M. El-Agnaf, S. Turnbull, M.J. German, K.E. Paleologou, Y. Hayashi, L.J.Cooper, N.J. Fullwood, D. Allsop. Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. J. Biol. Chem.,2005,280: 35789-35792.
[41]C.A. Marques, U. Keil, A. Bonert, B. Steiner, C. Haass, W.E. Muller, A. Eckert. Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation:oxidative stress, caspases, and the JNK pathway. J. Biol. Chem.2003,278:28294-28302.
[42]Y. Hashimoto, O. Tsuji, T. Niikura, Y. Yamagishi, M. Ishizaka, M. Kawasumi, T. Chiba, K. Kanekura, M. Yamada, E. Tsukamoto, K. Kouyama, K. Terashita, S. Aiso, A. Lin, I. Nishimoto. Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death. J. Neurochem.2003,84:864-877.
[43]E. Tamagno, M. Parola, P. Bardini, A. Piccini, R. Borghi, M. Guglielmotto, G. Santoro, A. Davit, O. Danni, M.A. Smith, G. Perry, M. Tabaton, β-Site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stressactivated protein kinases pathways. J. Neurochem.2005,92:628-636.
[44]C. Shen, Y. Chen, H. Liu, K. Zhang, T. Zhang, A. Lin, N. Jing, Hydrogen peroxide promotes A(3 production through JNK-dependent activation of y-secretase. J. Biol. Chem.2008,283:17721-17730.
[45]J.Z. Wang, F. Liu. Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog. Neurobiol,2008,85:148-175.
[46]M. Perez, M.A. Moran. I. Ferrer, J. Avila, P. Gomez-Ramos, Phosphorylated tau in neuritic plaques of APP(sw)/Tau (vlw) transgenic mice and Alzheimer disease. Acta Neuropathol.,2008,116:409-418.
[47]A.R. Saha, N.N. Ninkina, D.P. Hanger, B.H. Anderton, A.M. Davies, V.L. Buchman. Induction of neuronal death by a-synuclein. Eur. J.Neurosci.2000,12: 3073-3077.
[48]O.A. Levy, C. Malagelada, L.A. Greene, Cell death pathways in Parkinson's disease:proximal triggers, distal effectors, and final steps. Apoptosis,2009,14: 478-500.
[49]Heineke, J. and Molkentin, J. D. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat. Rev. Mol. Cell. Biol.2006,7:589-600.
[50]Bueno, O. F., DeWindt, L. J., Tymitz, K. M. et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 2000,19:6341-6350.
[51]Babu, G. J., Lalli, M. J., Sussman,M. A., Sadoshima, J. And Periasamy, M. Phosphorylation of elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy. J. Mol.Cell. Cardiol.2000,32: 1447-1457.
[52]Pfeffer, M. A. and Braunwald, E. (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation,1990,81: 1161-1172.
[53]Kaiser, R. A., Bueno, O. R, Lips, D. J. et al. Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo. J. Biol. Chem.2004,279:15524-15530.
[54]Ren, J., Zhang, S., Kovacs, A., Wang, Y. and Muslin, A. J. Role of p38a MAPK in cardiac apoptosis and remodeling after myocardial infarction. J. Mol. Cell. Cardiol. 2005,38:617-623.
[55]RUSSELL ROSS. ATHEROSCLEROSIS-AN INFLAMMATORY DISEASE. The New England Journal of Medicine.1999,340(2):115-126.
[56]Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol,2002,20:55-72.
[57]Jianhua Zhul, Ting Chen, Lin Yang, Zhoubin Li, Mei Mei Wong, Xiaoye Zheng, Xiaoping Pan, Li Zhang, Hui Yan. Regulation of MicroRNA-155 in Atherosclerotic Inflammatory Responses by Targeting MAP3K10. PLoS ONE 7(11):e46551. doi:10.1371/journal.pone.0046551.
[58]Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer,2003,3:11-22.
[59]Yaqing Zhang, Wei Yan, Meredith A. Collins, Filip Bednar, Sabita Rakshit, Bruce R. Zetter, Ben Z. Stanger, Ivy Chung, Andrew D. Rhim, and Marina Pasca di Magliano. Interleukin-6 Is Required for Pancreatic Cancer Progression by Promoting MAPK Signaling Activation and Oxidative Stress Resistance. Cancer Res,2013,73: 6359-6374.
[60]Andrea Glasauer, Laura A. Sena, Lauren P. Diebold, Andrew P. Mazar, and Navdeep S. Chandel Targeting SOD1 reduces experimental non-small-cell lung cancer. J Clin Invest.,2014,124(1):117-128.
[2]Bast A, Goris RJA. Oxidative stress. Biochemistry and human disease. Pharm. Weekbl.1989,11(6):199-206.
[3]Kelvin J.A. Davies. Oxidative stress:the paradox of aerobic life. Biochem. Soc. Symp.1995,61:1-30.
[4]Irwin Fridovich. Superoxide Dismutases. Annu. Rev. Biochem.1975,44: 147-159.
[5]Barry Halliwell. Reactive oxygen species in living systems:source, Biochemistry, and role in human disease. The American Journal of Medicine,1991,91(3C): 14s-22s.
[6]Christopher A. Papaharalambus and Kathy K. Griendling. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med.2007,17:48-54.
[7]Antonio Federico, Elena Cardaioli, Paola Pozza, et al. Mitochondria, oxidative stress and neurodegeneration. Journal of the Neurological Sciences,2012,322(1-2): 254-262.
[8]Chiara Cencioni, Francesco Spallotta, Fabio Martelli, et al. Oxidative stress and epigenetic regulation in ageing and age-related diseases. Int. J. Mol. Sci.,2013,14: 17643-17663
[9]Huige Li, Sven Horke, Ulrich Forstermann. Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacological Sciences,2012,34(6): 313-319.
[10]David Harrison, Kathy K Griendling, Ulf Landmesser, et al. Role of oxidative stress in atherosclerosis. The American Journal of Cardiology,2003,91(3):7-11.
[11]John W Baynes. Role of oxidative stress in development of complications in diabetes. Diabete,1991,40(4):405-412.
[12]A.C. Maritim, R.A. Sanders, J.B. Watkins. Diabetes, oxidative stress, and antioxidants:A review. Journal of Biochemical and Molecular Toxicology,2003, 17(1):24-38.
[13]A.B. Crujeiras, A. Diaz-Lagares, M.C. Carrera, et al. Oxidative stress associated to dysfunctional adipose tissue:a potential link between obesity, type 2 diabetes mellitus and breast cancer. Free Radical Research,2013,47(4):243-256.
[14]James E. Klauning, Lisa M. Kamendulis. The role of oxidative stress in carcinogenesis. Annual Review of Pharmacology and Toxicology,2004,44:239-267.
[15]William R. Markesbery. Oxidative stress hypothesis in Alzheimer's disease. Free Radical Biology and Medicine,1997,23(1):134-147.
[16]Antonio Federico, Elena Cardaioli, Paola Pozza, et al. Mitochondria, oxidative stress and neurodegeneration. Journal of the Neurological Sciences,2012,322(1-2): 254-262.
[17]Huige Li, Sven Horke, Ulrich Forstermann. Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacological Sciences,2013,34(6): 313-319.
[18]H.F. galley, N.R. Webster. Physiology of the endothelium. British Journal of Anaesthesia,2004,93(1):105-113.
[19]Yukihito Higashi, Kensuke Noma, Masao Yoshizumi, Yasuki Kihara. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal,2009,73: 411-418.
[20]Hua Cai, David G. Harrison. Endothelial dysfunction in cardiovascular diseases: the role of oxidative stress. Circulation Research,2000,87:840-844.
[21]Y Higashi, K Noma, M Yoshizumi, Y Kihara. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal,2009,73:411-418.
[22]Paul D. Ray, Bowen Huang, Yoshiaki Tsuji. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling,2012,24: 981-990.
[23]Toren Finkel. Signal transduction by reactive oxygen species. The Journal of Cell Biology,2011,194(1):7-15.
[24]J.T. Hancock, R. Desikan, S.J. Neill. Role of reactive oxygen species in cell signaling pathways. Biochemical and Biomedical Aspects of Oxidative Modification. 2001,29:345-350.
[25]Grag A. Knock, Jeremy P.T. Ward. Redox regulation of protein kinases as a modulator of vascular function. Antioxidants and Redox Signaling,2011,15(6): 1531-1546.
[26]Micheal E. Widlansky, David D. Gutterman. Regulation of endothelial function by mitochondrial reactive oxygen species. Antioxidants and Redox Signaling,2011, 15(6):1517-1530.
[27]N.C. Cook, S. Samman. Flavonoids-chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry,1996,7(2): 66-76.
[28]Elliott Middleton, JR, Chithan Kandaswami, Theoharis C. Theoharides. The effects of plant flavonoids on mammalian cells:implications of inflammation, heart disease, and cancer. Pharmacological Review,2000,52(4):673-751.
[29]Robert J. Williams, Jeremy P.E. Spencer. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radical Biology and Medicine,2012,52(1):35-45.
[30]Noriyoshi Masuoka, Maya Matsuda, Isao Kubo. Characterisation of the antioxidant activity of flavonoids. Food Chemistry,2012,131(2):541-545.
[31]Sam-Long Hwang, Ping-Hsiao Shih, Gow-Chin Yen. Neuroprotective effects of Citrus flavonoids. Journal of Agriculture and Food Chemistry,2012,60(4):877-885.
[32]Wei Dou, jingjing Zhang, Aning Sun, et al. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signaling. British Journal of Nutrition,2013,110(4):599-608.
[33]Changwu Xu, Jing Chen, Jing Zhang, et al. Naringenin inhibits vascular smooth muscle cell function involving reactive oxygen species production modulation and NF-κB activity suppression. Heart,2011,97(21):A83
[34]J. Yang, Q. Li, X.D. Zhou, et al. Naringenin attenuates muscous hypersecretion by modulating reactive oxygen production and inhibiting NF-κB activity via EGFR-PI3K-AKT7ERK MAPKinase signaling in human airway epithelial cells. Molecular and Cellular Biochemistry,2011,351(1-2):29-40.
[35]F.L. Yen, T.H. Wu, L.T. Lin, et al. Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-adminsttered rats with CCl4-induced acute liver failure. Pharmaceutical Research,2009,26(4):893-902.
[36]P.P. Trivedi, S. Kushwaha, D.N. Tripathi, et al. Cardioprotective effects of hesperetin against Doxorubicin-induced oxidative stress and DNA damage in rat. Cardiovascular Toxicology,2011,11(3):215-225.
[37]L. Paris, K. Shagirtha. Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats. Experimental and Toxicologic Pathology,2012, 64(5):513-520.
[38]S.L. Hwang, G.C. Yen. Effect of hesperetin against oxidative stress via ER-and TrkA-mediated action in PC 12 cells. Journal of Agriculture and Food Chemistry, 2011,59(10):5779-5785.
[39]G.D. Zhang, M.Z. Wang, and S.R. Zhang. Studies on the quantitative determination of farrerol in Man-shan-hong(Rhododendron Dauricum T.) leaves. Acta Pharmacol. Sin.1980,15(12):736-740.
[40], J.Z. Qiu, H. Xiang, C. Hu, et al. Subinhibitory concentrations of farrerol reduce a-toxin expression in Staphylococcus aureus. FEMS Microbiol. Lett.2011, 315(2):129-133.
[41]Z.T. Yang, Y.H. Fu, B. Liu, et al. Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus aureus internalization into bovine mammary epithelial cells. Microbial Pathogenesis,2013,65:1-6.
[42]Y. Xiong, S. Zhang, J. Lu, et al. Investigation of effects of farrerol on suppression of murine T lymphocyte activation in vitro and in vivo. International Immunopharmacology,2013,16(2):313-321.
[43]Li, Q.Y., Chen, L., Zhu, Y.H., Zhang, M., Wang, Y.P., and Wang, M.W. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacol. Sin.2011,32(4):433-440.
[1]Elliott Middleton, JR., Chithan Kandaswami, Theoharis C. Theoharides. The effects of plant flavonoids on mammalian cells:implications of inflammation, heart disease, and cancer. Pharmacological Review,2000,52(4):673-751.
[2]Robert J. Williams, Jeremy RE. Spencer. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radical Biology and Medicine,2012,52(1):35-45.
[3]Noriyoshi Masuoka, Maya Matsuda, Isao Kubo. Characterisation of the antioxidant activity of flavonoids. Food Chemistry,2012,131(2):541-545.
[4]G.D. Zhang, M.Z. Wang, and S.R. Zhang. Studies on the quantitative determination of farrerol in Man-shan-hong (Rhododendron Dauricum T.) leaves. Acta Pharmacol. Sin.1980,15(12):736-740.
[5], J.Z. Qiu, H. Xiang, C. Hu, et al. Subinhibitory concentrations of farrerol reduce a-toxin expression in Staphylococcus aureus. FEMS Microbiol. Lett.2011,315(2): 129-133.
[6]Z.T. Yang, Y.H. Fu, B. Liu, et al. Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus aureus intemalization into bovine mammary epithelial cells. Microbial Pathogenesis,2013,65:1-6.
[7]Y. Xiong, S. Zhang, J. Lu, et al. Investigation of effects of farrerol on suppression of murine T lymphocyte activation in vitro and in vivo. International Immunopharmacology,2013,16(2):313-321.
[8]Li, Q.Y., Chen, L., Zhu, Y.H., Zhang, M., Wang, Y.P., and Wang, M.W. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacol. Sin.2011,32(4):433-440.
[9]Hari Prasad Devkota, Masato Watanabe, Takashi Watanabe, and Shoji Yahara. Diplomorphanins A and B:New C-Methyl Flavonoids from Diplomorpha canescens. Chem. Pharm. Bull.,2013,61(2):242-244.
[10]Amer H. Tarawneh, Francisco Leon, Mohamed Ali Ibrahim, Sara Pettaway Christopher R. McCurdy, Stephen J. Cutler. Flavanones from Miconia prasina. Phytochemistry Letters,2014,7:130-132.
[11]Edgell, C.J., McDonald, C.C., and Graham, J.B. Permanent cell line expressing human factor Ⅷ-related antigen established by hybridization. Proc. Natl. Acad. Sci. U.S.A.1983,80(12):3734-3737.
[12]Edgell, C.J.S., Haizlip, J.E., Bagnell, C.R., Packenham, J.P., Harrison, P., Wilbourn, B., et al. Endothelium specific Weibel-Palade bodies in a continuous human cell line, EA.hy926. In Vitro Cell. Dev. Biol.1990,26(12):1167-1172.
[13]Diane, B., Geke, A.P.H., Coby, M., Grietje, M., and Nanno, M. Endothelium in vitro:a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis,2001,4(2):91-102.
[14]Yukihito Higashi, Kensuke Noma, Masao Yoshizumi, Yasuki Kihara. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal,2009,73: 411-418.
[15]Hua Cai, David G. Harrison. Endothelial dysfunction in cardiovascular diseases: the role of oxidative stress. Circulation Research,2000,87:840-844.
[16]Jia, L.Q., Yang, G.L., Ren, L., Chen, W.N., Feng, J.Y., Cao, Y., et al. Tanshinone IIA reduces apoptosis induced by hydrogen peroxide in the human endothelium-derived EA.hy926 cells.2012, J. Ethnopharmacol.143(1):100-108.
[17]Tim Mosmann. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods,1983,65:55-63.
[18]Bast A, Goris RJA. Oxidative stress. Biochemistry and human disease. Pharm. Weekbl.1989,11(6):199-206.
[19]Irwin Fridovich. Superoxide Dismutases. Annu. Rev. Biochem.1975,44: 147-159.
[20]Barry Halliwell. Reactive oxygen species in living systems:source, Biochemistry, and role in human disease. The American Journal of Medicine,1991,91(3C): 14s-22s.
[21]Christopher A. Papaharalambus and Kathy K. Griendling. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med.2007,17:48-54.
[22]Gawel, S., Wardas, M., Niedworok, E., and Wardas, P. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiad. Lek.2004,57(9-10):453-455.
[23]Lykkesfeldt, J. Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin. Chim. Acta,2007,380(1-2):50-58.
[24]Florence Caldefie-Chezet, Stephane Walrand, Christophe Moinard, Arlette Tridon, Jacques Chassagne, Marie-Paule Vasson. Is the neutrophil reactive oxygen species production measured by luminol and lucigenin chemiluminescence intra or extracellular? Comparison with DCFH-DA flow cytometry and cytochrome c reduction. Clinica Chimica Acta,2002,319:9-17.
[25]Rothe G, Valet G. Flow cytometry analysis of respiratory burst activity in phagocytes with hydroethidine and 2'-7'-dichlorofluorescin. J. Leukocyte. Biol.1990, 47:440-448.
[26]Joslyn K. Brunelle and Anthony Letai. Control of mitochondrial apoptosis by the Bcl-2 family. Journal of Cell Science,2009,122:437-441.
[27]Debra T. Chao and Stanley J. Korsmeyer. BCL-2 family:Regulators of Cell Death. Annual Review of Immunology.1998,16:395-419.
[28]Andreas Strasser, Liam O'Connor, and Vishva M. Dixit. Apoptosis signaling. Annu. Rev. Biochem.,2000,69:217-245.
[29]Stefan J. Riedl and Yigong Shi. Molecular mechanisms of caspase regulation during apoptosis. Molecular Cell Biology.2004,5:897-907.
[30]Imawati Budihardjo, Holt Oliver, Michael Lutter, Xu Luo, and Xiaodong Wang. BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS. Annual Review of Cell and Developmental Biology,1999,15: 269-290.
[31]Bazzoni, G, Dejana, E.. Endothelial cell-to-cell junctions:molecular organization and role in vascular homeostasis. Physiol. Rev.2004,84:869-901.
[32]Dejana, E., Corada, M., Lampugnani, M.G.. Endothelial cell-to-cell junctions. FASEB J.1995,9:910-918.
[33]Weis, S.M.. Vascular permeability in cardiovascular disease and cancer. Curr. Opin. Hematol.2008,15:243-249.
[34]Dejana, E., Elisabeth, T.L., Weinstein, B.M.. The control of vascular integrity by endothelial cell junctions:molecular basis and pathological implications. Dev. Cell 2009,16:209-221.
[35]Anderson, J.M., Italie, van C.M.. Tight junctions and the molecular basis for regulation of paracellular permeability. Am. J. Physiol.1995,269:G467-G475.
[36]Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., Tsukita, S.. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J. Cell Biol.1999,147:1351-1363.
[37]Hirase, T, Node, K.. Endothelial dysfunction as a cellular mechanism for vascular failure. Am. J. Physiol. Heart Circ. Physiol.2012,302:H499-H505.
[38]Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., Tsukita, S., Tsukita, S.. Occludin:a novel integral membrane protein localizing at tight junctions. J. Cell Biol.1993,123:1777-1788.
[39]Hirase T., Staddonl J.M., Saitou M., Ando-Akatsuka Y., Itoh M, Furuse M, Fujimoto K., Tsukita S., Rubin L.L., Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci.1997,110,1603-1613.
[40]CHRISTOPHER G. KEVIL, TADAYUKI OSHIMA, BRETT ALEXANDER, LAURA L. COE, and J. STEVEN ALEXANDER. H2O2-mediated permeability:role of MAPK and occludin. Am. J Physiol. Cell Physiol.2000,279:C21-C30.
[41]Balda, M.S., Anderson, J.M.. Two classes of tight junction are revealed by ZO-1 isoforms. Am. J. Physiol.1993,264:C918-C924.
[42]Willott, E., Balda, M.S., Heintzelman, M., Jameson, B, Anderson, J.M.. Localization and differential expression of two isoforms of the tight junction protein ZO-1. Am. J. Physiol. Cell Physiol.1992,262:C1119-C1124.
[43]Somrudee Chuenkitiyanon, Thitima Pengsuparp, and Suree Jianmongkol. Protective Effect of Quercetin on Hydrogen Peroxide-Induced Tight Junction Disruption. International Journal of Toxicology,2010,29(4) 418-424.
[44]Ponio JB-D, El-Ayoubi F, Glacial F, Ganeshamoorthy K, Driancourt C, et al. Instruction of Circulating Endothelial Progenitors In Vitro towards Specialized Blood-Brain Barrier and Arterial Phenotypes. PLoS ONE 2014,9(1):e84179. doi:10.1371/journal.pone.0084179
[1]Y. Zhang and C. Dong. Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci.,2007,64:2771-2789.
[2]Lufen Chang and Michael Karin. Mammalian MAP kinase signalling cascades. Nature,2001,410:37-40.
[3]John M. Kyriakis and Joseph Avruch. MAMMALIAN MAPK SIGNAL TRANSDUCTION PATHWAYS ACTIVATED BY STRESS AND INFLAMMATION:A 10-YEAR UPDATE. Physiol. Rev.,2012,92:689-737.
[4]Xiantao WANG, Jennifer L. MARTINDALE, Yusen LIU and Nikki J. HOLBROOK. The cellular response to oxidative stress:influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem. J., 1998,333:291-300.
[5]Kathryn Z. Guyton, Yusen Liu, Myriam Gorospe, Qingbo Xu, and Nikki J. Holbrook. Activation of Mitogen-activated Protein Kinase by H2O2. THE JOURNAL OF BIOLOGICAL CHEMISTRY,1996,271(8):4138-4142.
[6]Christopher Runchel, Atsushi Matsuzawa, and Hidenori Ichijo. Mitogen-Activated Protein Kinases in Mammalian Oxidative Stress Responses. Antioxidants & Redox Signaling,2011,15(1):205-218.
[7]Eun Su Jeon, Mi Jeong Lee, Sang-Min Sung, and Jae Ho Kim. Sphingosylphosphorylcholine Induces Apoptosis of Endothelial Cells Through Reactive Oxygen Species-Mediated Activation of ERK. Journal of Cellular Biochemistry,2007,100:1536-1547.
[8]Jin-Ran Chen, Lilian I. Plotkin, Jose'Ignacio Aguirre, Li Han, Robert L. Jilka, Stavroula Kousteni, Teresita Bellido, and Stavros C. Manolagas. Transient Versus Sustained Phosphorylation and Nuclear Accumulation of ERKs Underlie Anti-Versus Pro-apoptotic Effects of Estrogens. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2005,280(6):4632-4638.
[9]David Wan-Cheng Li, Jin-Ping Liu, Ying-Wei Mao, Hua Xiang, Juan Wang, Wei-Ya Ma. Zigang Dong, Helen M. Pike, Rhoderick E. Brown, and John C. Reed. Calcium-activated RAF/MEK/ERK Signaling Pathway Mediates p53-dependent Apoptosis and Is Abrogated by aB-Crystallin through Inhibition of RAS Activation. Molecular Biology of the Cell.2005,16:4437-4453.
[10]Shougang Zhuang, Yan Yan, Rebecca A. Daubert, Jiahuai Han, and Rick G. Schnellmann. ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells. Am J Physiol Renal Physiol 2007,292:F440-F447.
[11]JOHN M. KYRIAKIS AND JOSEPH AVRUCH. Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation. PHYSIOLOGICAL REVIEWS,2001,81(2):807-869.
[12]Joseph Schlessinger. Ligand-Induced, Receptor-Mediated Dimerization and Activation of EGF Receptor. Cell,2002,110,669-672.
[13]Mark A. Lemmonl, and Joseph Schlessinger. Cell Signaling by Receptor Tyrosine Kinases. Cell,2010,141:1117-1134.
[14]Sheila M. Thomas, Joan S. Brugge. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Biol.1977,13:513-609.
[15]Hong-Lin Chan, Hsiu-Chuan Chou, MaCarmen Duran, Jana Gruenewald, Michael D.Waterfield, Anne Ridley and John F. Timms. Major Role of Epidermal Growth Factor Receptor and Src Kinases in Promoting Oxidative Stress-dependent Loss of Adhesion and Apoptosis in Epithelial Cells. Journal of Biological Chemistry, 2010,285,4307-4318.
[16]Matthias Stein-Gerlach, Christian Wallasch, Axel Ullrich. SHP-2, SH2-containing protein tyrosine phosphatase-2. The International Journal of Biochemistry & Cell Biology,1998,30:559-66.
[17]Marie Dance. Alexandra Montagner, Jean-Pierre Salles, Armelle Yart, Patrick Raynal. The molecular function of SHP2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway. Cellular Signalling,2008,20:453-459.
[19]CHRISTOPHER G. KEVIL, TADAYUKI OSHIMA, BRETT ALEXANDER, LAURA L. COE, and J. STEVEN ALEXANDER. H:O2-mediated permeability:role of MAPK and occludin. Am. J Physiol. Cell Physiol.2000,279:C21-C30.
[1]S.M. Day, J.L. Reeve, D.D. Myers, W.P. Fay. Murine thrombosis models. Journal of Thrombosis and Haemostasis,2004,92 (3):486-494.
[2]Wei Li, ThomasM.McIntyre, RoyL.Silverstein. Ferric chloride-induced murine carotid arterial injury:A model of redox pathology. Redox Biology,2013,1:50-55.
[3]H.C. Whinna, Overview of murine thrombosis models. Thrombosis Research, 2008,122 (1):S64-S69.
[4]周光兴,高诚,徐平,姚明,谢家骏,胡建华主编, 人类疾病动物模型复制方法学,上海科学技术文献出版社,2008：27。
[5]Lubica Rauova. "Radical" model of thrombosis. Blood,2012,119:1798-1799.
[6]J. Sanz, P.R. Moreno, V. Fuster, The year in atherothrombosis, Journal of the American College of Cardiology 60 (10) (2012) 932-942.
[7]A. ECKLY, B. HECHLER, M. FREUND, M. ZERR, J.-P. CAZENAVE, F LANZA, P. H. MANGIN and C. GACHET. Mechanisms underlying FeCl3-induced arterial thrombosis. Journal of Thrombosis and Haemostasis,2011,9:779-789.
[8]L. Couture, L.P. Richer, M. Mercier, C. Helie, D. Lehoux, S.M. Hossain. Troubleshooting the rabbit ferric chloride-induced arterial model of thrombosis to assess in vivo efficacy of antithrombotic drugs. Journal of Pharmacological and Toxicological Methods,2013,67:91-97.
[9]Hulya Karatas, Sefik Evren Erdener, Yasemin Gursoy-Ozdemir, Gunfer Gurerl, Figen Soylemezoglu, Andrew K Dunn and Turgay Dalkara. Thrombotic distal middle cerebral artery occlusion produced by topical FeCl3 application:a novel model suitable for intravital microscopy and thrombolysis studies. Journal of Cerebral Blood Flow & Metabolism,2011,31:1452-1460.
[10]Lei Shi, Xiu E Feng, Jing Rong Cui, Lian Hua Fang, Guan Hua Du, Qing Shan Li. Synthesis and biological activity of flavanone derivatives. Bioorganic & Medicinal Chemistry Letters,2010,20:5466-5468.
[11]Bo-Nan Zhang, Yun-Long Hou, Bao-Jv Liu, Qing-Mei Liu and Guo-Fen Qiao. The Rhododendron dauricum L. Flavonoids Exert Vasodilation and Myocardial Preservation. Iranian Journal of Pharmaceutical Research.2010,9 (3):303-311
[12]Qun-yi LI, Li CHEN, Yan-hui ZHU, Meng ZHANG, Yi-ping WANG, Ming-wei WANG. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacologica Sinica 2011,32: 433-440.
[13]Zhang, G.W., Wang, L., Fu, P., and Hu, M.M. Mechanism and conformational studies of farrerol binding to bovine serum albumin by spectroscopic methods. Spectrochim. Acta A Mol. Biomol. Spectrosc.2011a,82(1):424-431.
[14]Zhang, G.W., Fu, P., Wang, L., and Hu, M.M. Molecular spectroscopic studies of farrerol interaction with calf thymus DNA. J. Agric. Food Chem.2011b,59(16): 8944-8952.
[15]Zhu, J.F., Li, D.J., Jin, J., and Wu, L.M. Binding analysis of farrerol to lysozyme by spectroscopic methods. Spectrochim. Acta A Mol. Biomol. Spectrosc.2007,68(2): 354-359.
[1]Barry Halliwell. Reactive oxygen species in living systems:source, Biochemistry, and role in human disease. The American Journal of Medicine,1991,91(3C): 14s-22s.
[2]Christopher A. Papaharalambus and Kathy K. Griendling. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends. Cardiovasc. Med.2007,17:48-54.
[3]Helmut Sies. Biochemistry of oxidative stress. Angew. Chem. Int. Ed. Engl.1986, 25:1058-1071.
[4]Bast A, Goris RJA. Oxidative stress. Biochemistry and human disease. Pharm. Weekbl.1989,11(6):199-206.
[5]Kelvin J.A. Davies. Oxidative stress:the paradox of aerobic life. Biochem. Soc. Symp.1995,61:1-30.
[6]Irwin Fridovich. Superoxide Dismutases. Annu. Rev. Biochem.1975,44: 147-159.
[7]Geiszt M., and Leto T.L.. The Nox family of NAD(P)H oxidases:host defense and beyond. J. Biol. Chem.2004,279:51715-51718.
[8]Miguel Antonio Aon, Brian Alan Stanley, Vidhya Sivakumaran, Jackelyn Melissa Kembro, Brian O'Rourke, Nazareno Paolocci, and Sonia Cortassa. Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission:An experimental-computational study. JGP,2012,139(6):479-185.
[9]Barry Halliwell and Susanna Chirico. Lipid peroxidation:its mechanism, measurement, and significance. Am. J. Clin. Nutr.,1993,57:715s-725s.
[10]John M.C. Gutteridge. Lipid peroxidation and antioxidants as biomarkers of tissue dange. Clin. Chem.,1995,41(12):1819-1829.
[11]ROBERT A. SCHWARTZMAN and JOHN CIDLOWSKI. Apoptosis:The biochemistry and molecular biology of programmed cell death. Endocrine Reviews, 1993,14(2):133-151.
[12]SUSAN ELMORE. Apoptosis:A review of programmed cell death. Toxicologic pathology,2007,35:495-516.
[13]Andreas Strasser, Liam O'Connor, and Vishva M. Dixit. Apoptosis signaling. Annu. Rev. Biochem.,2000,69:217-245.
[14]Imawati Budihardjo, Holt Oliver, Michael Lutter, Xu Luo, and Xiaodong Wang. BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS. Annual Review of Cell and Developmental Biology,1999,15:269-290.
[15]Avi Ashkenazi and Vishva M. Dixit. Death Receptors:Signaling and Modulation. Science,1998,281:1305-1308.
[16]T. Kaufmann, A. Strasser and P.J. Jost. Fas death receptor signalling:roles of Bid and XIAP. Cell Death and Differentiation,2012, (19):42-50.
[17]Dean P. Jones. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol,2008,295:C849-C868.
[18]Lei Cai, Hua Wang, Qin Li, Yunfei Qian, Wenbing Yao. Salidroside inhibits H2O2-induced apoptosis in PC 12 cells by preventing cytochrome c release and inactivating of caspase cascade. Acta Biochimica et Biophysica Sinica,2008,40(9): 796-802.
[19]L. Sun, HY Yan, WY Wong, RA Li, Y Huang, XQ Yao. Role of TRPM2 in H2O2-Induced Cell Apoptosis in Endothelial Cells. PLoS ONE, DOI: 10.1371/journal.pone.0043186.
[20]Shi-Yang Li, Xiao-Guang Wang, Ming-Ming Ma, Yun Liu, Yan-Hua Du, Xiao-Fei Lv, Jia-Guo Zhou, Yong-Bo Tang, Yong-Yuan Guan. Ginsenoside-Rd potentiates apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through the mitochondrial pathway. Apoptosis,2012,17(2):113-120.
[21]查锡良,主编,刘德培,主审,医学分子生物学(供研究生用),人民卫生出版社,2003：382-384.
[22]Y. Zhang and C. Dong. Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci.,2007,64:2771-2789.
[23]Kyriakis JM, Avruch J. Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation:A 10-Year Update. Physiol. Rev.,2012,92: 689-737.
[24]Long Chen, Lei Liu, Jun Yin, Yan Luo, Shile Huang. Hydrogen peroxide-induced neuronal apoptosis is associated with inhibition of protein phosphatase 2A and 5, leading to activation of MAPK pathway. The International Journal of Biochemistry and Cell Biology,2009,41(6):1248-1295.
[25]Zhong-Yan Zhao, Ping Luan, Shi-Xiong Huang, Song-Hua Xiao, Jia Zhao, Bei Zhang, Bei-Bei Gu, Rong-Biao Pi, Jun Liu. Edaravone Protects HT22 Neurons from H2O2-induced Apoptosis by Inhibiting the MAPK Signaling Pathway. CNS Neuroscience and Therapeutics,2013,19(3):163-169.
[26]Xiao Sun, Gui-bo Sun, Min Wang, Jing Xiao, Xiao-bo Sun. Protective effects of cynaroside against H2O2-induced apoptosis in H9c2 cardiomyoblasts. Journal of Cellular Biochemistry,2011,112(8):2019-2029.
[27]Paul D. Ray, Bo-Wen Huang, Yoshiaki Tsuji. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling,2012,24: 981-990.
[28]Chris M. Grant. Regulation of translation by Hydrogen peroxide. Antioxidants and redox signaling,2011,15(1):191-203.
[29]Baoshan Xu, Sujuan Chen, Yan Luo, Zi Chen, Lei Liu, Hongyu Zhou, Wenxing Chen, Tao Shen, Xiuzhen Han, Long Chen, Shile Huang. Calcium Signaling Is Involved in Cadmium-Induced Neuronal Apoptosis via Induction of Reactive Oxygen Species and Activation of MAPK/mTOR Network. PLoS ONE,2011,6(4):e19052. doi:10.1371/journal.pone.0019052
[30]Lorena Pereira, Ana Igea, Begona Canovas, Ignacio Dolado, Angel R. Nebreda. Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis mediated by reactive oxygen species and JNK. EMBO Molecular Medicine,2013, 5(11):1759-1774.
[31]Chia-Jung Hsieh, Po-Lin Kuo, Ying-Chan Hsu, Ya-Fang Huang, Eing-Mei Tsai, Ya-Ling Hsua. Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation. Free Radical Biology and Medicine,2014,67:159-170.
[32]Xu Wanga, Lei Cui, Jacob Joseph, Bingbing Jiang, David Pimental, Diane E. Handy, Ronglih Liao, Joseph Loscalzo. Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. Journal of Molecular and Cellular Cardiology,2012,52(3):753-760.
[33]Tien-Hui Lu, Shan-Yu Hsieh, Cheng-Chien Yen, Hsi-Chin Wu, Kuo-Liang Chen, Dong-Zong Hung, Chun-Hung Chen, Chin-Ching Wu, Yi-Chang Su, Ya-Wen Chen, Shing-Hwa Liu. Chun-Fa Huang. Involvement of oxidative stress-mediated ERK1/2 and p38 activation regulated mitochondria-dependent apoptotic signals in methylmercury-induced neuronal cell injury. Toxicology Letters,2011,204(1):71-80.
[34]John M. Kyriakis, Joseph Avruch. Mammalian MAPK signal transduction pathways activated by stress and inflammation:A 10-year update. Physiological Reviews,2012,92:689-737.
[35]Mervat Ibrahim Khairallah and Lobna Abdel Aal Kassem. Alzheimer's disease: Current status of etiopathogenesis and therapeutic strategies. Pakistan Journal of Biological Sciences,2011,14(4):257-272.
[36]Elena Anahi Bignante, Florencia Heredia, Gerardo Morfini, Alfredo Lorenzo. Amyloid p precursor protein as a molecular target for amyloid β-induced neuronal degeneration in Alzheimer's disease. Neurobiology of Aging,2013,34:2525-2537.
[37]M.T. Lin, M.F. Beal. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature,2006,443:787-795.
[38]D. Pratico. Oxidative stress hypothesis in Alzheimer's disease:a reappraisal. Trends Pharmacol. Sci., 2008,29:609-615.
[39]X. Zhu, H.G. Lee, A.K. Raina, G. Perry, M.A. Smith. The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals, 2002,11:270-281.
[40]B.J. Tabner, O.M. El-Agnaf, S. Turnbull, M.J. German, K.E. Paleologou, Y. Hayashi, L.J.Cooper, N.J. Fullwood, D. Allsop. Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. J. Biol. Chem.,2005,280: 35789-35792.
[41]C.A. Marques, U. Keil, A. Bonert, B. Steiner, C. Haass, W.E. Muller, A. Eckert. Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation:oxidative stress, caspases, and the JNK pathway. J. Biol. Chem.2003,278:28294-28302.
[42]Y. Hashimoto, O. Tsuji, T. Niikura, Y. Yamagishi, M. Ishizaka, M. Kawasumi, T. Chiba, K. Kanekura, M. Yamada, E. Tsukamoto, K. Kouyama, K. Terashita, S. Aiso, A. Lin, I. Nishimoto. Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death. J. Neurochem.2003,84:864-877.
[43]E. Tamagno, M. Parola, P. Bardini, A. Piccini, R. Borghi, M. Guglielmotto, G. Santoro, A. Davit, O. Danni, M.A. Smith, G. Perry, M. Tabaton, β-Site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stressactivated protein kinases pathways. J. Neurochem.2005,92:628-636.
[44]C. Shen, Y. Chen, H. Liu, K. Zhang, T. Zhang, A. Lin, N. Jing, Hydrogen peroxide promotes A(3 production through JNK-dependent activation of y-secretase. J. Biol. Chem.2008,283:17721-17730.
[45]J.Z. Wang, F. Liu. Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog. Neurobiol,2008,85:148-175.
[46]M. Perez, M.A. Moran. I. Ferrer, J. Avila, P. Gomez-Ramos, Phosphorylated tau in neuritic plaques of APP(sw)/Tau (vlw) transgenic mice and Alzheimer disease. Acta Neuropathol.,2008,116:409-418.
[47]A.R. Saha, N.N. Ninkina, D.P. Hanger, B.H. Anderton, A.M. Davies, V.L. Buchman. Induction of neuronal death by a-synuclein. Eur. J.Neurosci.2000,12: 3073-3077.
[48]O.A. Levy, C. Malagelada, L.A. Greene, Cell death pathways in Parkinson's disease:proximal triggers, distal effectors, and final steps. Apoptosis,2009,14: 478-500.
[49]Heineke, J. and Molkentin, J. D. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat. Rev. Mol. Cell. Biol.2006,7:589-600.
[50]Bueno, O. F., DeWindt, L. J., Tymitz, K. M. et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 2000,19:6341-6350.
[51]Babu, G. J., Lalli, M. J., Sussman,M. A., Sadoshima, J. And Periasamy, M. Phosphorylation of elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy. J. Mol.Cell. Cardiol.2000,32: 1447-1457.
[52]Pfeffer, M. A. and Braunwald, E. (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation,1990,81: 1161-1172.
[53]Kaiser, R. A., Bueno, O. R, Lips, D. J. et al. Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo. J. Biol. Chem.2004,279:15524-15530.
[54]Ren, J., Zhang, S., Kovacs, A., Wang, Y. and Muslin, A. J. Role of p38a MAPK in cardiac apoptosis and remodeling after myocardial infarction. J. Mol. Cell. Cardiol. 2005,38:617-623.
[55]RUSSELL ROSS. ATHEROSCLEROSIS-AN INFLAMMATORY DISEASE. The New England Journal of Medicine.1999,340(2):115-126.
[56]Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol,2002,20:55-72.
[57]Jianhua Zhul, Ting Chen, Lin Yang, Zhoubin Li, Mei Mei Wong, Xiaoye Zheng, Xiaoping Pan, Li Zhang, Hui Yan. Regulation of MicroRNA-155 in Atherosclerotic Inflammatory Responses by Targeting MAP3K10. PLoS ONE 7(11):e46551. doi:10.1371/journal.pone.0046551.
[58]Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer,2003,3:11-22.
[59]Yaqing Zhang, Wei Yan, Meredith A. Collins, Filip Bednar, Sabita Rakshit, Bruce R. Zetter, Ben Z. Stanger, Ivy Chung, Andrew D. Rhim, and Marina Pasca di Magliano. Interleukin-6 Is Required for Pancreatic Cancer Progression by Promoting MAPK Signaling Activation and Oxidative Stress Resistance. Cancer Res,2013,73: 6359-6374.
[60]Andrea Glasauer, Laura A. Sena, Lauren P. Diebold, Andrew P. Mazar, and Navdeep S. Chandel Targeting SOD1 reduces experimental non-small-cell lung cancer. J Clin Invest.,2014,124(1):117-128.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |