清心饮对佐剂性关节炎心血管损伤的保护作用及部分机制研究
|
摘要
目的:近年来,随着皮质激素、免疫抑制剂治疗的应用,类风湿关节炎(rheumatoid arthritis,RA)患者的生存期得到明显延长,与此同时心血管并发症也逐渐增多。心血管疾病成为RA患者的首要死亡原因。因此探索其发病机理及防治措施成为RA临床治疗中亟待解决的重要问题之一。本课题拟研究清心饮对佐剂性关节炎(adjuvant arthritis,AA)大鼠离体血管内皮依赖性舒张功能及其对同型半胱氨酸(homocysteine, Hcy)、血管细胞间粘附分子-1(vascular cell adhesion molecule-1,VCAM-1 )、内皮素-1 ( endothelin-1, ET-1)、肿瘤坏死因子(tumor necrosis factor-α, TNF-α)、白介素-1β(interleukin-1β, IL-1β)表达的影响,研究其血管保护作用机制,为临床用药提供实验依据。
方法:选择体重150-180g的Wistar大鼠,雌雄各半。测量双侧足爪容积后,于右后足跖部常规消毒,皮内注射完全弗氏佐剂(0.1ml/只)建立AA大鼠模型。其中10只大鼠用相同方法注入等量生理盐水。造模后第19天将出现二次反应的大鼠随机分为模型组、甲氨喋呤(MTX)组、MTX+清心饮(MTX+QXY)组,每组10只。注入生理盐水组为空白对照组。当日测量大鼠体重、用自制容积测量仪测量各组大鼠足爪容积。各治疗组连续灌胃给药(模型组灌胃给予等量生理盐水)21天,于给药结束后第2天测量各组大鼠足爪容积、体重后,3%戊巴比妥麻醉,腹主动脉取血,分别留取血清、血浆。放射免疫法检测大鼠血浆ET-1,血清TNF-α、IL-1β,ELISA法检测血清VCAM-1,循环酶法检测血清Hcy;取血后立即打开胸腔,取出胸主动脉,分离周围脂肪及结缔组织,保留血管内皮,截取长为3-4mm的主动脉环,主动脉环浴皿法检测内皮依赖性舒张功能;剩余部分动脉,经固定、脱水、包埋、染色,免疫组织化学法检测血管内皮细胞VCAM-1的表达。
统计学处理:所有数据均采用SPSS for windows 13.0软件包进行统计学处理,所得结果均以X±S表示。各组间均数比较采用单因素方差分析。
结果:
1 QXY对AA大鼠一般情况的影响
与模型组比较,MTX组、MTX+QXY组一般情况均有所改善。造模后,模型组、MTX组与MTX+QXY组体重明显低于空白对照组(P<0.01),但模型组、MTX组与MTX+QXY组间无差异(P>0.05);灌胃完毕,模型组、MTX组与MTX+QXY组体重明显低于空白对照组(P<0.01),模型组与MTX组明显低于MTX+QXY组(P<0.01),模型组明显低于MTX组(P<0.01);MTX、模型组体重增加明显低于空白对照组(P<0.01),MTX、模型组体重增加明显低于MTX+QXY组(P<0.01),MTX+QXY组体重增加值与空白对照组比较无显著性差异(P>0.05),模型组体重增加明显低于MTX组(P<0.01)。
2 QXY对AA大鼠足爪肿胀的抑制作用
给药3周后,MTX组、MTX+QXY组造模侧足爪平均肿胀度明显低于模型组(P<0.01),MTX组与MTX+QXY组比较无明显差异(P>0.05),但MTX+QXY组对造模侧肿胀足爪的抑制率稍优于MTX组(58.20% VS 54.7%)。(2)MTX组、MTX+QXY组非造模侧平均肿胀度明显低于模型组(P<0.01),MTX+QXY组与MTX组比较无显著差异(P>0.05),但MTX+QXY组对非造模侧肿胀足爪的抑制率稍优于MTX组(48.49% VS 44.20%)。
3 QXY对AA大鼠内皮依赖性舒张功能的影响
主动脉环对乙酰胆碱(acetylcholine, Ach)引起的内皮依赖性舒张作用(%)各个浓度(10-9 mmol/L、10-8 mmol/L、10-7 mmol/L、10-6 mmol/L)中模型组、MTX组、MTX+QXY组均明显低于空白对照组,差异有显著性(P<0.01、0.05),模型组、MTX组明显低于MTX+QXY组(P<0.01);从10-8 mmol/L开始,模型组明显低于MTX组,差异有显著性(P<0.05、0.01)。主动脉环对硝普钠(sodiumnitroprusside, NaNP)引起的非内皮依赖性舒张作用(%)中前两个浓度(即10-9mmol/L、10-8mmol/L)各组间存在明显差异,显著性水平从0.05到0.01不等,后两个浓度(10-7 mmol/L、10-6 mmol/L)各组间均无明显差异(P>0.05)。
4 QXY对AA大鼠对血清TNF-α、IL-1β,血浆ET-1,血清
Hcy,血清及血管内皮细胞VCAM-1的影响4.1血清TNF-α、IL-1β水平比较,模型组、MTX组明显高于空白对照组(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.01),MTX+QXY组与空白对照组比较无明显差异(P>0.05),模型组明显高于MTX组(P<0.01);4.2血浆ET-1水平比较,模型组、MTX组与MTX+QXY组明显高于空白对照组(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.05),模型组与MTX组比较无明显差异(P>0.05)。4.3.1血清VCAM-1水平比较,模型组、MTX组明显高于空白对照组(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.01),MTX+QXY组与空白对照组无显著差异(P>0.05),模型组明显高于MTX组(P<0.01)。4.3.2动脉内皮细胞VCAM-1(灰度值)比较,模型组、MTX组明显高于空白对照组,差异有显著性(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.05),模型组明显高于MTX组,差异有显著性(P<0.01),MTX+QXY组与空白对照组比较无明显差异(P>0.05)。4.4血清Hcy水平比较,模型组、MTX组与MTX+QXY组明显高于空白对照组,差异有显著性(P<0.01),模型组、MTX组明显高于MTX+QXY组,差异有显著性(P<0.01),模型组与MTX组比较无明显差异(P>0.05)。
结论:
1 AA大鼠血清Hcy、VCAM-1及血浆ET-1水平明显升高,主动脉内皮依赖性舒张功能明显下降,说明AA大鼠存在心血管损害的相关因素。
2清心饮具有显著抗炎作用。清心饮联合MTX可明显降低AA大鼠足爪肿胀度及血清炎性细胞因子TNF-α、IL-1β水平。
3清心饮对AA大鼠血管内皮损伤具有保护作用。清心饮可明显改善AA大鼠主动脉内皮依赖性舒张功能,降低血浆ET-1,血清VCAM-1、Hcy水平,减少胸主动脉内皮细胞VCAM-1的表达,从而改善AA大鼠血管内皮损伤。
Objective: Using with glucocorticoid and immunodepressive drug in these years, the life of Rheumatoid Arthritis(RA) patients has been prolonged. At the same time, the number of RA patients with cardiovascular disease is increasing. And cardiovascular disease has became the first reason in RA patients’death. Thus, investigating the mechanism in it and the precautionary measure became one of the cardinal problem in RA clinical treatment. The aim of the study is to investigate the effect of QingXinYin to relaxant response depend on endothelium of isolated aortas, homocysteine(Hcy), vascular cell adhesion molecule-1(VCAM-1), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and endothelin-1 (ET-1) to investigate the protective mechanism and afford experimental evidence for clinical work.
Methods: Choose Wistar rats weight from 150g to 180g, the number of male and female is equal. Injecting Freund’s complete adjuvant(FCA) into the subcutis of their right rear paws after sterilizing regularly is to found AA rat models and ten of rats are injected equivalent volume of saline. On the 19th day after injecting, rats that presenting secondary response are divided randomly into Model group, MTX group, MTX&QXY group, and each group includes 10 samples. The rats injected saline were as control group. After measuring the paw volumes and weights of rats in each group, the treatment rats are given drug for successive 21 days. On the second day after treatment is over, after measuring the paw volumes and the weights, rats are sacrificed by withdraw of blood by abdominal aortas under 3% pentobarbital sodium anesthesia to get serum and plasma. ET-1, TNF-α, IL-1βare determined by radioimmunoassay, VCAM-1 by ELISA, Hcy by cyclical zyme technique. After drawing blood, thorax was cut open and removed thoracic aortas quickly. Then, it was cleared of adherent fatty and connective tissue, and was scissored rings of 3-4mm length. Determining relaxant response depend on endothelium by technique of aortas in organ chambers. The remanent part of aortas was fixed, dehydrated, wrapped and dyed to determine VCAM-1 in vascular endothelium cell by immunohistochemical.
Data Statistics: All data is analysed by SPSS for windows 13.0 and the results are expressed as X±S. The comparison of mean among groups is evaluated by one-way analysis of variance(ANOVA)
Results:
1 The effect of MTX&QXY to general condition of AA rats Comparing with model group, MTX group and MTX&QXY group are increased in general condition. After model founded, the weight of model group, MTX group and MTX&QXY group is lower than control group significantly(P<0.01), but there is no significant difference among the AA three groups. At the end of the experiment, the weight of model group, MTX group and MTX&QXY group is still lower than control group significantly(P<0.01), model group and MTX group is lower than MTX&QXY group significantly(P<0.01), and model group is lower than MTX group significantly(P<0.01). The augment of MTX group and model group is lower than control group and MTX&QXY group in weight significantly(P<0.01), model group is lower than MTX group significantly(P < 0.01), but there is no significant difference between control group and MTX&QXY group(P>0.05).
2 The depressive effect of QXY to paw swelling of AA rats At the end of experiment, the average swelling degree(%) of FCA-injected paws of MTX group and MTX&QXY group is lower than model group significantly(P<0.01), and MTX group is parallel with MTX&QXY group(P>0.05). The average swelling degrees(%) of non-FCA-injected paws of MTX group and MTX&QXY group is lower than model group significantly(P < 0.01), and MTX group is parallel with MTX&QXY group(P>0.05).
3 The effect of QXY to relaxation depend on endothelium of AA rats
The acetylcholine(Ach) induced endothelium dependent relaxation are decreased in aortas from AA rats, and model group and MTX group is lower than MTX&QXY group significantly(P<0.01), model group is lower than MTX group significantly(P<0.01 or 0.05). The sodiumnitroprusside(NaNP) induced endothelium independent relaxation has no significant difference among groups in AA rats(P>0.05).
4 The effect of QXY to TNF-αand IL-1βin serum, ET-1 in plasma and VCAM-1 in serum and vascular endothelium cell of AA rats
4.1 Comparing the level of TNF-αand IL-1βin serum, model group and MTX group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.01), model group is higher than MTX group significantly(P<0.01), but there is no significant difference between MTX&QXY group and control group(P>0.05).
4.2 Comparing the level of ET-1 in plasma, model group ,MTX group and MTX&QXY group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.05), and there is no significant difference between model group and MTX group(P>0.05).
4.3.1 Comparing the level of VCAM-1 in serum, model group and MTX group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.01), model group is higher than MTX group significantly(P < 0.01), and there is no significant difference between MTX&QXY group and control group(P>0.05).
4.3.2 Comparing the level of VCAM-1 in vascular endothelium cell, model group and MTX group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.05), model group is higher than MTX group significantly(P<0.01), and there is no significant difference between MTX&QXY group and control group(P>0.05).
4.4 Comparing the level of Hcy in serum, model group, MTX group and MTX&QXY group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.01), and there is no significant difference between model group and MTX group(P>0.05).
Conclusions:
1 Hcy and VCAM-1 in serum and ET-1 in plasma are all increased significantly, and relaxation dependent on endothelium is decreased significantly. They all confirm that AA rats have many factors engendering cardiovascular dysfunction.
2 QingXinYin can resist inflammation positively. QingXinYin combine with MTX can remedy AA significantly, decrease the paw swelling and the level of inflammatory cell factors such as TNF-αand IL-1β.
3 QingXinYin can protect vascular dysfunction of AA rats. QingXinYin increase relaxation dependent on endothelium, decrease ET-1 in plasma, VCAM-1 and Hcy in serum and VCAM-1 in vascular endothelium cell to protect endothelium dysfunction in AA rats’vascular.
方法:选择体重150-180g的Wistar大鼠,雌雄各半。测量双侧足爪容积后,于右后足跖部常规消毒,皮内注射完全弗氏佐剂(0.1ml/只)建立AA大鼠模型。其中10只大鼠用相同方法注入等量生理盐水。造模后第19天将出现二次反应的大鼠随机分为模型组、甲氨喋呤(MTX)组、MTX+清心饮(MTX+QXY)组,每组10只。注入生理盐水组为空白对照组。当日测量大鼠体重、用自制容积测量仪测量各组大鼠足爪容积。各治疗组连续灌胃给药(模型组灌胃给予等量生理盐水)21天,于给药结束后第2天测量各组大鼠足爪容积、体重后,3%戊巴比妥麻醉,腹主动脉取血,分别留取血清、血浆。放射免疫法检测大鼠血浆ET-1,血清TNF-α、IL-1β,ELISA法检测血清VCAM-1,循环酶法检测血清Hcy;取血后立即打开胸腔,取出胸主动脉,分离周围脂肪及结缔组织,保留血管内皮,截取长为3-4mm的主动脉环,主动脉环浴皿法检测内皮依赖性舒张功能;剩余部分动脉,经固定、脱水、包埋、染色,免疫组织化学法检测血管内皮细胞VCAM-1的表达。
统计学处理:所有数据均采用SPSS for windows 13.0软件包进行统计学处理,所得结果均以X±S表示。各组间均数比较采用单因素方差分析。
结果:
1 QXY对AA大鼠一般情况的影响
与模型组比较,MTX组、MTX+QXY组一般情况均有所改善。造模后,模型组、MTX组与MTX+QXY组体重明显低于空白对照组(P<0.01),但模型组、MTX组与MTX+QXY组间无差异(P>0.05);灌胃完毕,模型组、MTX组与MTX+QXY组体重明显低于空白对照组(P<0.01),模型组与MTX组明显低于MTX+QXY组(P<0.01),模型组明显低于MTX组(P<0.01);MTX、模型组体重增加明显低于空白对照组(P<0.01),MTX、模型组体重增加明显低于MTX+QXY组(P<0.01),MTX+QXY组体重增加值与空白对照组比较无显著性差异(P>0.05),模型组体重增加明显低于MTX组(P<0.01)。
2 QXY对AA大鼠足爪肿胀的抑制作用
给药3周后,MTX组、MTX+QXY组造模侧足爪平均肿胀度明显低于模型组(P<0.01),MTX组与MTX+QXY组比较无明显差异(P>0.05),但MTX+QXY组对造模侧肿胀足爪的抑制率稍优于MTX组(58.20% VS 54.7%)。(2)MTX组、MTX+QXY组非造模侧平均肿胀度明显低于模型组(P<0.01),MTX+QXY组与MTX组比较无显著差异(P>0.05),但MTX+QXY组对非造模侧肿胀足爪的抑制率稍优于MTX组(48.49% VS 44.20%)。
3 QXY对AA大鼠内皮依赖性舒张功能的影响
主动脉环对乙酰胆碱(acetylcholine, Ach)引起的内皮依赖性舒张作用(%)各个浓度(10-9 mmol/L、10-8 mmol/L、10-7 mmol/L、10-6 mmol/L)中模型组、MTX组、MTX+QXY组均明显低于空白对照组,差异有显著性(P<0.01、0.05),模型组、MTX组明显低于MTX+QXY组(P<0.01);从10-8 mmol/L开始,模型组明显低于MTX组,差异有显著性(P<0.05、0.01)。主动脉环对硝普钠(sodiumnitroprusside, NaNP)引起的非内皮依赖性舒张作用(%)中前两个浓度(即10-9mmol/L、10-8mmol/L)各组间存在明显差异,显著性水平从0.05到0.01不等,后两个浓度(10-7 mmol/L、10-6 mmol/L)各组间均无明显差异(P>0.05)。
4 QXY对AA大鼠对血清TNF-α、IL-1β,血浆ET-1,血清
Hcy,血清及血管内皮细胞VCAM-1的影响4.1血清TNF-α、IL-1β水平比较,模型组、MTX组明显高于空白对照组(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.01),MTX+QXY组与空白对照组比较无明显差异(P>0.05),模型组明显高于MTX组(P<0.01);4.2血浆ET-1水平比较,模型组、MTX组与MTX+QXY组明显高于空白对照组(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.05),模型组与MTX组比较无明显差异(P>0.05)。4.3.1血清VCAM-1水平比较,模型组、MTX组明显高于空白对照组(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.01),MTX+QXY组与空白对照组无显著差异(P>0.05),模型组明显高于MTX组(P<0.01)。4.3.2动脉内皮细胞VCAM-1(灰度值)比较,模型组、MTX组明显高于空白对照组,差异有显著性(P<0.01),模型组、MTX组明显高于MTX+QXY组(P<0.05),模型组明显高于MTX组,差异有显著性(P<0.01),MTX+QXY组与空白对照组比较无明显差异(P>0.05)。4.4血清Hcy水平比较,模型组、MTX组与MTX+QXY组明显高于空白对照组,差异有显著性(P<0.01),模型组、MTX组明显高于MTX+QXY组,差异有显著性(P<0.01),模型组与MTX组比较无明显差异(P>0.05)。
结论:
1 AA大鼠血清Hcy、VCAM-1及血浆ET-1水平明显升高,主动脉内皮依赖性舒张功能明显下降,说明AA大鼠存在心血管损害的相关因素。
2清心饮具有显著抗炎作用。清心饮联合MTX可明显降低AA大鼠足爪肿胀度及血清炎性细胞因子TNF-α、IL-1β水平。
3清心饮对AA大鼠血管内皮损伤具有保护作用。清心饮可明显改善AA大鼠主动脉内皮依赖性舒张功能,降低血浆ET-1,血清VCAM-1、Hcy水平,减少胸主动脉内皮细胞VCAM-1的表达,从而改善AA大鼠血管内皮损伤。
Objective: Using with glucocorticoid and immunodepressive drug in these years, the life of Rheumatoid Arthritis(RA) patients has been prolonged. At the same time, the number of RA patients with cardiovascular disease is increasing. And cardiovascular disease has became the first reason in RA patients’death. Thus, investigating the mechanism in it and the precautionary measure became one of the cardinal problem in RA clinical treatment. The aim of the study is to investigate the effect of QingXinYin to relaxant response depend on endothelium of isolated aortas, homocysteine(Hcy), vascular cell adhesion molecule-1(VCAM-1), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and endothelin-1 (ET-1) to investigate the protective mechanism and afford experimental evidence for clinical work.
Methods: Choose Wistar rats weight from 150g to 180g, the number of male and female is equal. Injecting Freund’s complete adjuvant(FCA) into the subcutis of their right rear paws after sterilizing regularly is to found AA rat models and ten of rats are injected equivalent volume of saline. On the 19th day after injecting, rats that presenting secondary response are divided randomly into Model group, MTX group, MTX&QXY group, and each group includes 10 samples. The rats injected saline were as control group. After measuring the paw volumes and weights of rats in each group, the treatment rats are given drug for successive 21 days. On the second day after treatment is over, after measuring the paw volumes and the weights, rats are sacrificed by withdraw of blood by abdominal aortas under 3% pentobarbital sodium anesthesia to get serum and plasma. ET-1, TNF-α, IL-1βare determined by radioimmunoassay, VCAM-1 by ELISA, Hcy by cyclical zyme technique. After drawing blood, thorax was cut open and removed thoracic aortas quickly. Then, it was cleared of adherent fatty and connective tissue, and was scissored rings of 3-4mm length. Determining relaxant response depend on endothelium by technique of aortas in organ chambers. The remanent part of aortas was fixed, dehydrated, wrapped and dyed to determine VCAM-1 in vascular endothelium cell by immunohistochemical.
Data Statistics: All data is analysed by SPSS for windows 13.0 and the results are expressed as X±S. The comparison of mean among groups is evaluated by one-way analysis of variance(ANOVA)
Results:
1 The effect of MTX&QXY to general condition of AA rats Comparing with model group, MTX group and MTX&QXY group are increased in general condition. After model founded, the weight of model group, MTX group and MTX&QXY group is lower than control group significantly(P<0.01), but there is no significant difference among the AA three groups. At the end of the experiment, the weight of model group, MTX group and MTX&QXY group is still lower than control group significantly(P<0.01), model group and MTX group is lower than MTX&QXY group significantly(P<0.01), and model group is lower than MTX group significantly(P<0.01). The augment of MTX group and model group is lower than control group and MTX&QXY group in weight significantly(P<0.01), model group is lower than MTX group significantly(P < 0.01), but there is no significant difference between control group and MTX&QXY group(P>0.05).
2 The depressive effect of QXY to paw swelling of AA rats At the end of experiment, the average swelling degree(%) of FCA-injected paws of MTX group and MTX&QXY group is lower than model group significantly(P<0.01), and MTX group is parallel with MTX&QXY group(P>0.05). The average swelling degrees(%) of non-FCA-injected paws of MTX group and MTX&QXY group is lower than model group significantly(P < 0.01), and MTX group is parallel with MTX&QXY group(P>0.05).
3 The effect of QXY to relaxation depend on endothelium of AA rats
The acetylcholine(Ach) induced endothelium dependent relaxation are decreased in aortas from AA rats, and model group and MTX group is lower than MTX&QXY group significantly(P<0.01), model group is lower than MTX group significantly(P<0.01 or 0.05). The sodiumnitroprusside(NaNP) induced endothelium independent relaxation has no significant difference among groups in AA rats(P>0.05).
4 The effect of QXY to TNF-αand IL-1βin serum, ET-1 in plasma and VCAM-1 in serum and vascular endothelium cell of AA rats
4.1 Comparing the level of TNF-αand IL-1βin serum, model group and MTX group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.01), model group is higher than MTX group significantly(P<0.01), but there is no significant difference between MTX&QXY group and control group(P>0.05).
4.2 Comparing the level of ET-1 in plasma, model group ,MTX group and MTX&QXY group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.05), and there is no significant difference between model group and MTX group(P>0.05).
4.3.1 Comparing the level of VCAM-1 in serum, model group and MTX group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.01), model group is higher than MTX group significantly(P < 0.01), and there is no significant difference between MTX&QXY group and control group(P>0.05).
4.3.2 Comparing the level of VCAM-1 in vascular endothelium cell, model group and MTX group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.05), model group is higher than MTX group significantly(P<0.01), and there is no significant difference between MTX&QXY group and control group(P>0.05).
4.4 Comparing the level of Hcy in serum, model group, MTX group and MTX&QXY group is higher than control group significantly(P<0.01), model group and MTX group is higher than MTX&QXY group significantly(P<0.01), and there is no significant difference between model group and MTX group(P>0.05).
Conclusions:
1 Hcy and VCAM-1 in serum and ET-1 in plasma are all increased significantly, and relaxation dependent on endothelium is decreased significantly. They all confirm that AA rats have many factors engendering cardiovascular dysfunction.
2 QingXinYin can resist inflammation positively. QingXinYin combine with MTX can remedy AA significantly, decrease the paw swelling and the level of inflammatory cell factors such as TNF-αand IL-1β.
3 QingXinYin can protect vascular dysfunction of AA rats. QingXinYin increase relaxation dependent on endothelium, decrease ET-1 in plasma, VCAM-1 and Hcy in serum and VCAM-1 in vascular endothelium cell to protect endothelium dysfunction in AA rats’vascular.
引文
1 叶任高,陆再英.内科学,第 6 版. 北京:人民卫生出版社.2004:885
2 吴智鸿,赵水平.类风湿关节炎与冠心病.中华风湿病学杂志,2004,8:688
3 李佃贵,李振彬,林慧芳,等. 清心饮抗心肌缺血作用的实验研究.河北中医杂志,2002,24:71-73
4 李振彬,李佃贵,靳文龙,等. 清心饮对大鼠心肌缺血及SOD 和 MDA 的影响.中成药,2003,25:160-161
5 李振彬,李佃贵,李俊侠,等. 清心饮对在体大鼠心肌缺血再灌注损伤的保护作用. 中成药,2004,26:2-4
6 蒋明,DAVID YU,林孝义. 中华风湿病学.华夏出版社. 2004:592-593
7 Van Dcornum S, McColl G, Wicks IP. Accelerated atherosclerosis:an extra articular feature of rheumatoid arthritis?Arthritis Rheum, 2002,46:862-873
8 Del Rincon ID, Williams K, Stern MP, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional risk factors. Arthritis Rheum, 2001,44:2737-2745
9 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation, 2000,102:2165-2168
10 Pascen V, Cheng JS, Willerson JI, et al. Modulation of C-reactive protein mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation, 2001,103:2531-2534
11 Mendall MA, Palel P, Ballam L, et al. C-reactive protein and its relation to cardiovascular risk factor:a population based cross sectional study. BMJ, 1996,312:1061-1065
12 曹建平,张晓晨,姜志名,等. 血浆内皮素-1 及降钙素基因相关肽与类风湿关节炎的相关分析. 现代康复,2001,5:73
13 苏茵,马本良,王波兰,等. 血浆内皮素的测定在类风湿关节炎中的意义. 临床内科杂志,2002,19:111
14 石晓彤,王晓非,蒋莉,等. 类风湿关节炎患者血浆中 ET和 CGRP 的变化及意义. 细胞与分子免疫学杂志,2001,17:531-532
15 Janice Z, Robert F, Denise M, et al. Diagnostic marker cooperative study for the diagnosis of MI. Circ ,1999:1671-1677
16 Kang SS, Wong PW, Malinow MR. Hyperhomocysteinemia as a risk factor for occlusive vascular disease. Ann Rev Natr,1992,12:279-298
17 Boushey CJ, Beresford SAA , Omenn BS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA, 1995,274: 1049-1057
18 Blundell G, Jones BG, Rose FA, et al. Homocyteine mediated endothelial cell toxicity and its amelioration. Arteriosclerosis, 1996,122:201-216
19 田青平,刘乃奎,汤健,等. 同型半胱氨酸促进平滑肌细胞 增 殖 的 内 信 号 传 递 途 径 . 中 华 医 学 杂 志 ,2000,80:152-154
20 Sparrow CP, Olszewski J. Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ione. J Lipid Res, 1993,34:1219-1228
21 Myllykangas Luosujarvi R, Aho K, Kautiainen H, et al. Cardiovascular mortality in women with rheumatoid arthritis. J Rheumatoid, 1995,22:1065-1067
22 徐晓龚,周卫华,肖传实,等. 风湿性疾病中高同型半胱氨酸血症的临床研究. 中华内科杂志,2005,44:111-114
23 Kunitomo M, Yamaguchi Y, Futagawa Y, et al. Lipid deposition in the aorta of adjuvant arthritis rats with hypercholesterolemia. Jpn-J-Pharmacol, 1986,42:261-267
24 Yoshisuke Haruna, Yoshitaka Morita, Norio Komai, et al. Endothelial dysfunction in rat adjuvant-induced arthritis. Arthritis & Rheumatism, 2006,54:1847-1855
25 Cenk Can, Mehtap G, Cinar, et al. Vascular endothelial dysfunction associated with elevated serum homocysteine levels in rat adjuvant arthritis: effect of vitamin E administration. Life sciences,2002,71:401-410
26 Naveed S, David WM, Hilary C, et al. Explaining how “high grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis.Circulation,2003,108:2957
27 Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002,359:1173-1177.
28 Jacobsson LTH, Turesson C, Gulfe A, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005,32:1213-1218
29 Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.Circulation,2002,106:2184
30 Hansel S, Lassig G, Pistrosch F, et al. Endothelial dysfunction in young patients with long-term rheumatoidarthritis and low disease activity. Atherosclerosis,2003,170:177
31 Bloom BJ, Miller LC, Tucher LB, et al. Soluble adhesion molecules in juvenile rheumatoid arthritis. J Rheumatol,1999,26:2044
32 吴贻谷,宋立人主编. 中华本草. 上海. 上海科技出版社,1996:1766-1767
33 秦凤华,谢蜀生,张文仁,等. 白花蛇舌草对小鼠免疫功能的增强作用. 上海免疫学杂志,1990,10:321
34 Azzaw IM, Hasleton P. Tumor necrosis factor alpha and the cardiovascular system:its role in cardiac allograft rejection and heart disease. Cardiovasc Res, 1999,43:850-859
35 张萌,张伯礼,高秀梅,等. 丹参酸 B 和丹参酮ⅡA 不同配比对肿瘤坏死因子-α 损伤大鼠心脏微血管内皮细胞的影响. 中草药,2004,35:63-65
36 Herrmann J, Lerman LG, Rodrigned Porcel M, et al. Coronary rasa vasorum neovascularization recedes opiacardial endothelial dysfunction in experimental hypercholesterolemia. Cardiovasc Res, 2001,51:762-766
37 Rafn S, Evden D. Therapentic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med, 2003,9:702-712
38 Targonski PV, Ronelti PO, Pumper GM,et al. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation, 2003,107:2805-2809
39 Graham IM, Daly LE, Refsum HM, et al.Hyperhomocysteinemia is a risk factor for vascular disease. The European Concerted Action Project. JAMA, 1997,277:1775-1781
40 Berman RS, Martin W. Arteial endothelial barrier dysfunction : actions of homocysteine and the hypoxanthine-xanthine oxedase free radical generatin system. Br J Pharmacol, 1993,108:920-926
41 Harker LA, Ross R, Slichter SJ, et al. Homocystein-induced arteriosclerosis:the role of endothelial cell injury and platelet response in its genesis. J Clin Invest, 1976,58:731-741
42 Chambers JC, Obeid OA, Kooner JS. Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal subjects. Arterioscler Thromb Vasc Biol, 1999,19:2922-2927
43 Zhang C, Cai Y, Anachi MT, et al. Homocystein induces programmed cell death innuman vascular endothelial cells in rough activation of the untolded protein response. J Biol Chem, 2001,275:35867-35874
44 Upchurch GR Jr,Welch GN, Fabian AJ, et al. J Biol Chem, 1997,272:17012-17017
45 Zhang X, Li H, Jin H, et al. Am J Physiol Renal Physiol, 2000,279:671-678
46 Kiowaski W, Sutsch G, Hunziker P, et al. Evidence for endothelin-1-mediated, vasoconst-reaction,in seven chronic heart failure. Lancet, 1995,346:735
47 Gottster A, Anwar I, Eriksson K F, et al. Homocysteine isrelated to neopterin and endothelin-1 in plasma of subjects with disturb glucose metabolism and reference subjects. Angiology, 2000,51:489-497
48 Hirata Y, Takagi Y, Fukuda Y, et al. Endothelin is a potent mitogen for rat vascular smooth cell. Atherosclerosis, 1989,78:225
49 Nakaki T, Nakayama M, Yamamoto S, et al. Endothelin mediated stimulation of DNA synthesis in vascular smooth muscle. Biochem Biophy Res Commun, 1989,158:880
50 郑建杰,马爱群,王鸿雁,等. 动脉粥样硬化与 VCAM-1及 CD36 关 系 的 实 验 研 究 . 陕 西 医 学 杂 志 ,2005,34:1451-1456
51 徐荣良,张国元,秦永文,等. 高血脂兔主动脉黏附分子VCAM-1 基因表达的研究. 第二军医大学学报,1999,20:950-952
52 吴华香,王彩花,朱永良,等. 活动性类风湿关节炎患者sICAM-1、sVCAM-1 的变化及意义. 中国免疫学杂志,2003,19:645-647
1 叶任高,陆再英.内科学第 6 版.北京人民卫生出版社,2004:885
2 蒋明,朱立平,林孝义.风湿病学.科学出版社,1995:861
3 孙毅.类风湿关节炎并发心血管系统损害 43 例临床分析.长春大学学报, 2002,12:26-27
4 Luosujarvi M K, Aho K, Kautianen H, et al. Cardiovascular mortality in women with rheumatoid arthritis. J Rheumatol, 1999,22:1065-1067
5 Gabriel S E, Crowson C S, O Fallon W M. Comorbidity in arthritis. J Rheumatol, 1999,26:2475-2479
6 Del Rincon I D, Williams K, Stern M P, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum, 2001,44:2737-2745
7 Banks M, Flinr, Bacon P A, et al. Rheumatoid arthritis is an independent risk factor for ischalmic heart disease. Arthritis Rheum, 2000, 43(suppl 9):S385
8 Bank M J, Pace A, Kitas G D. A cute coronary syndroms present atypically and recur more frequently in rheumatoid arthritis than matched controls. Arthritis Rheum, 2001,44(suppl):S53
9 S. Van Doornum, C. Brand, B. King, et al. Increased case fatality rate following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis & Rheumatism, 2006,54:2061-2068
10 Kunitomo M, Yamaguchi Y, Futagawa Y, et al. Lipid deposition in the aorta of adjuvant arthritis rats with hypercholesterolemia. Jpn-J-Pharmacol, 1986,42:261-267
11 Hansel S, Lassig G, Pistrosch F, et al. Endothelial dysfunction in young patients with long-term rheumatoid arthritis and low disease activity. Atherosclerosis, 2003,170(1):177-180
12 Yoshisuke Haruna, Yoshitake Morita, Norio Komai, et al. Endothelial Dysfunction in Rat Adjuvant-Induced Arthritis. Arthritis & Rheumatism,2006,54:1847-1855
13 Park Y B, Ahn C W, Choi H K, et al. Atherosclerosis in rheumatoid arthritis: morpho-logic evidence obtained by carotid ultrasound. Arthritis Rheum, 2002,46(7):1714-1479
14 Del Rincon I, Williams K, Stern M P, et al. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum, 2003,48(7):1833-1840
15 Bloom B J, Miller L C, Tucker L B, et al. Soluble adhesion molecules in juvenile rheumatoid arthritis. J Rheumatol, 1999,26:2044-2048
16 Veale D J, Maple C, Kirk G,et al. Soluble cell adhesion molecules P-selection and ICAM-1, and disease activity inpatients receiving sulphasalazine for active rheumatoid arthritis. Scand J Rheumatol, 1998,27:296-299
17 Khovidhunkit W, Memon R A, Feingold K R, et al. Infection and inflammation-induced proatherogenic changes of lipoproteins. J Infect Dis, 2000,181(supple 3):462-472
18 Munro R, Morrison E, Mc Donald A G, et al. Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis. Ann Rheum Dis, 1997,56:374-377
19 Hrut-Camejo E, Paredes S, Masana L, et al. Elevated levels of small low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile. Arthritis Rheum, 2001,44:2761-2767
20 Winyard P G, Tatzber T, Esterbauer H, et al. Presence of foam cells containing oxidized low density lipoprotein in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum Dis, 1993,52(9):677-680
21 Cisternas M, Gutierrez M A, Klaassen J, et al. Cardiovascular risk factors in children patients with rheumatoid arthritis. J Rheumatol, 2002,29(8):1619-1622
22 Lazzerini P E, Cappeechi P L, Bisogno S, et al. Reduction in plasma bomocysteine level in patients with rheumatoid arthritis given pulsed glucocorticoid treatment. Ann Rheum Dis, 2003,62:694-695
23 Cenk Can, Mehap G. Cinar, Sezen kosay, et al. Vascular endothelial dysfunction associated with elevated serumhomocysteine levels in rat adjuvant arthritis: effect of vitamin E administration. Life Sciences, 2002,71:401-410
24 Hallgren R, Berne C. Glucose intolerance in patients with chronic inflammatory diseases is normalized by glucocorticoids. Acta Med Scand, 1983,213:351-355
25 Kiortsis D N, Mavridis A K, Vasakos S, et al. Effects of infliximab treatment on insuline resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann-Rheum Dis, 2005,64(5):765-766
26 Gonzalaz Gay M A, De Matias J M, Gonzalez Juanatey C, et al. Anti-tumor necrosis factor-alpha blockade improves in patients with rheumatoid arthritis. Clin-Exp-Rheumatol, 2006,24(1):83-86
27 Mc Entegart A, Capell H A, Creran D, et al. Cardiovasclular risk factors, including thrombotic variables, in a population with rheumatoid arthritis. Rheumatology, 2001,40:640-641
28 Motalban J, Rio J, Khamastha A, et al. Value of immunologic testing in stroke patients: a prospective multicenter study. Stroke, 1994,25(12):2412
29 Tohgi H, Takahashi H, Kashiwaya M, et al. Anticardiolipoin antibody in elderly stroke patients: its effects on stroke types, recurrence and the coagulation fibrinolysis system. Acta Neurol Scand, 1994,90(2):86
30 Serneri N G, Prisco D, Martini F, et al. Acute T-cell activation is detectable in unstable angina. Circulation, 1997,95:1806-1812
31 van der Wal A C, Piek J J, de Boer O J, et al. Recent activation of the plague immune response in coronary lesions underlying acute coronary syndromes. Heart, 1998,80:14-18
32 Liuzzo G, Kopecky S L, Frye R L, et al. Perturbation of the T-cell repertoire in patients with unstable angina. Circulation, 1999,100:2135-2139
33 Choi H K, Hernan M A, Seeger J D, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet, 2002,359:1173-1177
34 Daniel H. Solomon, Jerry Avorn, Jeffrey N, et al. Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis. Arthritis & Rheumatism,2006,54:3790-3798
35 Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-α treatment improves endothelial function in patients with rheumatoid arthritis. Circulation,2002,106:2184-2187
36 Gonazalez Juanatey C, Testa A, Garcia Castelo A, et al. Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor-α antibody. Arthritis Rheum,2004,51:447-450
37 王娟,赵龙吟. 动脉粥样硬化过程中的炎症反应. 分子心脏病学杂志,2004,18(4):238-242
38 李建华,张慧芳,刘敏,等. 早期辛伐他汀治疗对急性脑梗死患者血脂和炎症反应标志物 C-反应蛋白浓度的影响. 北京医学,2006,28:354-356
39 陈弹,程绪杰,杨向军,等. 辛伐他汀对冠心病的抗炎作用. 中国新药与临床杂志,2003,22:720-722
40 黄清春,张声鹏,徐秋英,等. 复方丹参对Ⅱ型胶原蛋白诱导模型滑膜细胞分泌及肿瘤坏死因子的影响. 现代康复,2001,5(10):54-55
41 黄清春,徐秋英,接力刚,等. 复方丹参对Ⅱ型胶原蛋白诱导性关节炎大鼠滑膜细胞白介素-6mRNA 表达的影响. 中国临床康复,2002,6:1585-1586
42 文川,徐浩,黄启福,等. 几种活血中药对 ApoE 缺血小鼠动脉粥样硬化斑块的影响. 中国病理生理杂志,2005,21(5):864-867
43 戴敏,刘青云,訾晓梅. 丹皮酚对高脂血症大鼠动脉内皮细胞的保护作用. 中国中医基础医学杂志, 2001,7(2):38
2 吴智鸿,赵水平.类风湿关节炎与冠心病.中华风湿病学杂志,2004,8:688
3 李佃贵,李振彬,林慧芳,等. 清心饮抗心肌缺血作用的实验研究.河北中医杂志,2002,24:71-73
4 李振彬,李佃贵,靳文龙,等. 清心饮对大鼠心肌缺血及SOD 和 MDA 的影响.中成药,2003,25:160-161
5 李振彬,李佃贵,李俊侠,等. 清心饮对在体大鼠心肌缺血再灌注损伤的保护作用. 中成药,2004,26:2-4
6 蒋明,DAVID YU,林孝义. 中华风湿病学.华夏出版社. 2004:592-593
7 Van Dcornum S, McColl G, Wicks IP. Accelerated atherosclerosis:an extra articular feature of rheumatoid arthritis?Arthritis Rheum, 2002,46:862-873
8 Del Rincon ID, Williams K, Stern MP, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional risk factors. Arthritis Rheum, 2001,44:2737-2745
9 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation, 2000,102:2165-2168
10 Pascen V, Cheng JS, Willerson JI, et al. Modulation of C-reactive protein mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation, 2001,103:2531-2534
11 Mendall MA, Palel P, Ballam L, et al. C-reactive protein and its relation to cardiovascular risk factor:a population based cross sectional study. BMJ, 1996,312:1061-1065
12 曹建平,张晓晨,姜志名,等. 血浆内皮素-1 及降钙素基因相关肽与类风湿关节炎的相关分析. 现代康复,2001,5:73
13 苏茵,马本良,王波兰,等. 血浆内皮素的测定在类风湿关节炎中的意义. 临床内科杂志,2002,19:111
14 石晓彤,王晓非,蒋莉,等. 类风湿关节炎患者血浆中 ET和 CGRP 的变化及意义. 细胞与分子免疫学杂志,2001,17:531-532
15 Janice Z, Robert F, Denise M, et al. Diagnostic marker cooperative study for the diagnosis of MI. Circ ,1999:1671-1677
16 Kang SS, Wong PW, Malinow MR. Hyperhomocysteinemia as a risk factor for occlusive vascular disease. Ann Rev Natr,1992,12:279-298
17 Boushey CJ, Beresford SAA , Omenn BS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA, 1995,274: 1049-1057
18 Blundell G, Jones BG, Rose FA, et al. Homocyteine mediated endothelial cell toxicity and its amelioration. Arteriosclerosis, 1996,122:201-216
19 田青平,刘乃奎,汤健,等. 同型半胱氨酸促进平滑肌细胞 增 殖 的 内 信 号 传 递 途 径 . 中 华 医 学 杂 志 ,2000,80:152-154
20 Sparrow CP, Olszewski J. Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ione. J Lipid Res, 1993,34:1219-1228
21 Myllykangas Luosujarvi R, Aho K, Kautiainen H, et al. Cardiovascular mortality in women with rheumatoid arthritis. J Rheumatoid, 1995,22:1065-1067
22 徐晓龚,周卫华,肖传实,等. 风湿性疾病中高同型半胱氨酸血症的临床研究. 中华内科杂志,2005,44:111-114
23 Kunitomo M, Yamaguchi Y, Futagawa Y, et al. Lipid deposition in the aorta of adjuvant arthritis rats with hypercholesterolemia. Jpn-J-Pharmacol, 1986,42:261-267
24 Yoshisuke Haruna, Yoshitaka Morita, Norio Komai, et al. Endothelial dysfunction in rat adjuvant-induced arthritis. Arthritis & Rheumatism, 2006,54:1847-1855
25 Cenk Can, Mehtap G, Cinar, et al. Vascular endothelial dysfunction associated with elevated serum homocysteine levels in rat adjuvant arthritis: effect of vitamin E administration. Life sciences,2002,71:401-410
26 Naveed S, David WM, Hilary C, et al. Explaining how “high grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis.Circulation,2003,108:2957
27 Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002,359:1173-1177.
28 Jacobsson LTH, Turesson C, Gulfe A, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005,32:1213-1218
29 Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.Circulation,2002,106:2184
30 Hansel S, Lassig G, Pistrosch F, et al. Endothelial dysfunction in young patients with long-term rheumatoidarthritis and low disease activity. Atherosclerosis,2003,170:177
31 Bloom BJ, Miller LC, Tucher LB, et al. Soluble adhesion molecules in juvenile rheumatoid arthritis. J Rheumatol,1999,26:2044
32 吴贻谷,宋立人主编. 中华本草. 上海. 上海科技出版社,1996:1766-1767
33 秦凤华,谢蜀生,张文仁,等. 白花蛇舌草对小鼠免疫功能的增强作用. 上海免疫学杂志,1990,10:321
34 Azzaw IM, Hasleton P. Tumor necrosis factor alpha and the cardiovascular system:its role in cardiac allograft rejection and heart disease. Cardiovasc Res, 1999,43:850-859
35 张萌,张伯礼,高秀梅,等. 丹参酸 B 和丹参酮ⅡA 不同配比对肿瘤坏死因子-α 损伤大鼠心脏微血管内皮细胞的影响. 中草药,2004,35:63-65
36 Herrmann J, Lerman LG, Rodrigned Porcel M, et al. Coronary rasa vasorum neovascularization recedes opiacardial endothelial dysfunction in experimental hypercholesterolemia. Cardiovasc Res, 2001,51:762-766
37 Rafn S, Evden D. Therapentic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med, 2003,9:702-712
38 Targonski PV, Ronelti PO, Pumper GM,et al. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation, 2003,107:2805-2809
39 Graham IM, Daly LE, Refsum HM, et al.Hyperhomocysteinemia is a risk factor for vascular disease. The European Concerted Action Project. JAMA, 1997,277:1775-1781
40 Berman RS, Martin W. Arteial endothelial barrier dysfunction : actions of homocysteine and the hypoxanthine-xanthine oxedase free radical generatin system. Br J Pharmacol, 1993,108:920-926
41 Harker LA, Ross R, Slichter SJ, et al. Homocystein-induced arteriosclerosis:the role of endothelial cell injury and platelet response in its genesis. J Clin Invest, 1976,58:731-741
42 Chambers JC, Obeid OA, Kooner JS. Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal subjects. Arterioscler Thromb Vasc Biol, 1999,19:2922-2927
43 Zhang C, Cai Y, Anachi MT, et al. Homocystein induces programmed cell death innuman vascular endothelial cells in rough activation of the untolded protein response. J Biol Chem, 2001,275:35867-35874
44 Upchurch GR Jr,Welch GN, Fabian AJ, et al. J Biol Chem, 1997,272:17012-17017
45 Zhang X, Li H, Jin H, et al. Am J Physiol Renal Physiol, 2000,279:671-678
46 Kiowaski W, Sutsch G, Hunziker P, et al. Evidence for endothelin-1-mediated, vasoconst-reaction,in seven chronic heart failure. Lancet, 1995,346:735
47 Gottster A, Anwar I, Eriksson K F, et al. Homocysteine isrelated to neopterin and endothelin-1 in plasma of subjects with disturb glucose metabolism and reference subjects. Angiology, 2000,51:489-497
48 Hirata Y, Takagi Y, Fukuda Y, et al. Endothelin is a potent mitogen for rat vascular smooth cell. Atherosclerosis, 1989,78:225
49 Nakaki T, Nakayama M, Yamamoto S, et al. Endothelin mediated stimulation of DNA synthesis in vascular smooth muscle. Biochem Biophy Res Commun, 1989,158:880
50 郑建杰,马爱群,王鸿雁,等. 动脉粥样硬化与 VCAM-1及 CD36 关 系 的 实 验 研 究 . 陕 西 医 学 杂 志 ,2005,34:1451-1456
51 徐荣良,张国元,秦永文,等. 高血脂兔主动脉黏附分子VCAM-1 基因表达的研究. 第二军医大学学报,1999,20:950-952
52 吴华香,王彩花,朱永良,等. 活动性类风湿关节炎患者sICAM-1、sVCAM-1 的变化及意义. 中国免疫学杂志,2003,19:645-647
1 叶任高,陆再英.内科学第 6 版.北京人民卫生出版社,2004:885
2 蒋明,朱立平,林孝义.风湿病学.科学出版社,1995:861
3 孙毅.类风湿关节炎并发心血管系统损害 43 例临床分析.长春大学学报, 2002,12:26-27
4 Luosujarvi M K, Aho K, Kautianen H, et al. Cardiovascular mortality in women with rheumatoid arthritis. J Rheumatol, 1999,22:1065-1067
5 Gabriel S E, Crowson C S, O Fallon W M. Comorbidity in arthritis. J Rheumatol, 1999,26:2475-2479
6 Del Rincon I D, Williams K, Stern M P, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum, 2001,44:2737-2745
7 Banks M, Flinr, Bacon P A, et al. Rheumatoid arthritis is an independent risk factor for ischalmic heart disease. Arthritis Rheum, 2000, 43(suppl 9):S385
8 Bank M J, Pace A, Kitas G D. A cute coronary syndroms present atypically and recur more frequently in rheumatoid arthritis than matched controls. Arthritis Rheum, 2001,44(suppl):S53
9 S. Van Doornum, C. Brand, B. King, et al. Increased case fatality rate following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis & Rheumatism, 2006,54:2061-2068
10 Kunitomo M, Yamaguchi Y, Futagawa Y, et al. Lipid deposition in the aorta of adjuvant arthritis rats with hypercholesterolemia. Jpn-J-Pharmacol, 1986,42:261-267
11 Hansel S, Lassig G, Pistrosch F, et al. Endothelial dysfunction in young patients with long-term rheumatoid arthritis and low disease activity. Atherosclerosis, 2003,170(1):177-180
12 Yoshisuke Haruna, Yoshitake Morita, Norio Komai, et al. Endothelial Dysfunction in Rat Adjuvant-Induced Arthritis. Arthritis & Rheumatism,2006,54:1847-1855
13 Park Y B, Ahn C W, Choi H K, et al. Atherosclerosis in rheumatoid arthritis: morpho-logic evidence obtained by carotid ultrasound. Arthritis Rheum, 2002,46(7):1714-1479
14 Del Rincon I, Williams K, Stern M P, et al. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum, 2003,48(7):1833-1840
15 Bloom B J, Miller L C, Tucker L B, et al. Soluble adhesion molecules in juvenile rheumatoid arthritis. J Rheumatol, 1999,26:2044-2048
16 Veale D J, Maple C, Kirk G,et al. Soluble cell adhesion molecules P-selection and ICAM-1, and disease activity inpatients receiving sulphasalazine for active rheumatoid arthritis. Scand J Rheumatol, 1998,27:296-299
17 Khovidhunkit W, Memon R A, Feingold K R, et al. Infection and inflammation-induced proatherogenic changes of lipoproteins. J Infect Dis, 2000,181(supple 3):462-472
18 Munro R, Morrison E, Mc Donald A G, et al. Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis. Ann Rheum Dis, 1997,56:374-377
19 Hrut-Camejo E, Paredes S, Masana L, et al. Elevated levels of small low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile. Arthritis Rheum, 2001,44:2761-2767
20 Winyard P G, Tatzber T, Esterbauer H, et al. Presence of foam cells containing oxidized low density lipoprotein in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum Dis, 1993,52(9):677-680
21 Cisternas M, Gutierrez M A, Klaassen J, et al. Cardiovascular risk factors in children patients with rheumatoid arthritis. J Rheumatol, 2002,29(8):1619-1622
22 Lazzerini P E, Cappeechi P L, Bisogno S, et al. Reduction in plasma bomocysteine level in patients with rheumatoid arthritis given pulsed glucocorticoid treatment. Ann Rheum Dis, 2003,62:694-695
23 Cenk Can, Mehap G. Cinar, Sezen kosay, et al. Vascular endothelial dysfunction associated with elevated serumhomocysteine levels in rat adjuvant arthritis: effect of vitamin E administration. Life Sciences, 2002,71:401-410
24 Hallgren R, Berne C. Glucose intolerance in patients with chronic inflammatory diseases is normalized by glucocorticoids. Acta Med Scand, 1983,213:351-355
25 Kiortsis D N, Mavridis A K, Vasakos S, et al. Effects of infliximab treatment on insuline resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann-Rheum Dis, 2005,64(5):765-766
26 Gonzalaz Gay M A, De Matias J M, Gonzalez Juanatey C, et al. Anti-tumor necrosis factor-alpha blockade improves in patients with rheumatoid arthritis. Clin-Exp-Rheumatol, 2006,24(1):83-86
27 Mc Entegart A, Capell H A, Creran D, et al. Cardiovasclular risk factors, including thrombotic variables, in a population with rheumatoid arthritis. Rheumatology, 2001,40:640-641
28 Motalban J, Rio J, Khamastha A, et al. Value of immunologic testing in stroke patients: a prospective multicenter study. Stroke, 1994,25(12):2412
29 Tohgi H, Takahashi H, Kashiwaya M, et al. Anticardiolipoin antibody in elderly stroke patients: its effects on stroke types, recurrence and the coagulation fibrinolysis system. Acta Neurol Scand, 1994,90(2):86
30 Serneri N G, Prisco D, Martini F, et al. Acute T-cell activation is detectable in unstable angina. Circulation, 1997,95:1806-1812
31 van der Wal A C, Piek J J, de Boer O J, et al. Recent activation of the plague immune response in coronary lesions underlying acute coronary syndromes. Heart, 1998,80:14-18
32 Liuzzo G, Kopecky S L, Frye R L, et al. Perturbation of the T-cell repertoire in patients with unstable angina. Circulation, 1999,100:2135-2139
33 Choi H K, Hernan M A, Seeger J D, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet, 2002,359:1173-1177
34 Daniel H. Solomon, Jerry Avorn, Jeffrey N, et al. Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis. Arthritis & Rheumatism,2006,54:3790-3798
35 Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-α treatment improves endothelial function in patients with rheumatoid arthritis. Circulation,2002,106:2184-2187
36 Gonazalez Juanatey C, Testa A, Garcia Castelo A, et al. Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor-α antibody. Arthritis Rheum,2004,51:447-450
37 王娟,赵龙吟. 动脉粥样硬化过程中的炎症反应. 分子心脏病学杂志,2004,18(4):238-242
38 李建华,张慧芳,刘敏,等. 早期辛伐他汀治疗对急性脑梗死患者血脂和炎症反应标志物 C-反应蛋白浓度的影响. 北京医学,2006,28:354-356
39 陈弹,程绪杰,杨向军,等. 辛伐他汀对冠心病的抗炎作用. 中国新药与临床杂志,2003,22:720-722
40 黄清春,张声鹏,徐秋英,等. 复方丹参对Ⅱ型胶原蛋白诱导模型滑膜细胞分泌及肿瘤坏死因子的影响. 现代康复,2001,5(10):54-55
41 黄清春,徐秋英,接力刚,等. 复方丹参对Ⅱ型胶原蛋白诱导性关节炎大鼠滑膜细胞白介素-6mRNA 表达的影响. 中国临床康复,2002,6:1585-1586
42 文川,徐浩,黄启福,等. 几种活血中药对 ApoE 缺血小鼠动脉粥样硬化斑块的影响. 中国病理生理杂志,2005,21(5):864-867
43 戴敏,刘青云,訾晓梅. 丹皮酚对高脂血症大鼠动脉内皮细胞的保护作用. 中国中医基础医学杂志, 2001,7(2):38