通络汤抗动脉粥样硬化作用的实验研究
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摘要
目的
动脉粥样硬化是一种慢性的动脉疾病,发病人群以老年人居多。动脉粥样硬化可导致冠心病、心绞痛、心肌梗死、脑血栓、脑出血、脑萎缩、痴呆等多种疾病,严重危害人类的健康。通络汤具有益气补肾、活血通络的功效,用于临床效果较好。为了进一步研究其对动脉硬化的早期防治作用,本实验观察了通络汤对动脉粥样硬化(As)大鼠的作用效果,并探讨其抗As的可能作用机制。
方法
SPF级纯种Wistar大鼠60只,雌雄各半,体重170±20g,随机分成6组,每组10只。即正常对照组、高脂饲料组、通心络胶囊组、通络汤低、中、高剂量组。在造模过程中即开始给药。通络汤浓缩液(由黄石市中医院提供,常规煎煮):高浓度2.7g/ml、中浓度1.35g/ml、低浓度0.675g/ml;通心络胶囊配置成混悬液,浓度为2.05%。上述各组均按1ml/100g体重的剂量于每日早8时灌胃,每日一次。连续给药10周后,禁食12小时,断头取血,检测大鼠血脂浓度、血清NO、血浆血栓素B_2(TXB_2)、6-Keto-PGF_(1α)水平,并取主动脉作病理学检查。
结果
1、一般指标的变化
正常组大鼠毛色光泽,活动自如,反应灵敏,饮食正常。高脂饲料组体重增长较快,皮下脂肪厚,但随实验进程,毛发色泽暗淡,活动减少,反应迟钝,精神状态较差,进食量减少。通心络胶囊组较对照组活动稍有减少、反应尚灵敏、皮毛光泽、进食量稍有减少。通络汤高、中剂量组活动稍有减少,反应灵敏,皮毛尚光泽,食欲稍有减退。通络汤低剂量组活动减少,反应欠灵敏,皮毛色泽暗淡,食欲减退。
2、TC、TG、LDL、HDL的变化
高脂饲料组TC、TG、LDL较正常对照组明显升高(p＜0.01),HDL降低(p＜0.01);通心络胶囊组及通络汤各剂量组总TC、TG、LDL较高脂饲料组显著降低(p＜0.01),而HDL升高(p＜0.01)。通络汤高剂量组与通心络胶囊组相比无差别。
3、血清NO的变化
高脂饲料组NO浓度较正常对照组显著降低(p＜0.01)。通心络胶囊组、通络汤中、高剂量组NO显著升高(p＜0.01)。通络汤中、高剂量组与通心络胶囊组相比无差别。
4、血浆6-Keto-PGF_1α和TXB_2的变化
高脂饲料组血浆6-Keto-PGF_1α水平较正常组显著降低,TCB_2、TXB_2/PGF_(1α)显著升高(p＜0.01);通络汤各剂量组血浆6-Keto-PGF_(1α)水平较高脂组均显著升高(p＜0.01),通心络胶囊组及通络汤各剂量组血浆TXB_2,TXB_2/PGF_1α的水平均显著降低(p＜0.01);通络汤各剂量组血浆6-Keto-PGF_(1α)水平较通心络胶囊组均有显著差别,中、高剂量组血浆TXB_2水平无显著差别,各剂量组TXB_2/PGF_(1α)的水平无显著差别。
5、胸主动脉形态学改变
5.1肉眼观察:正常组血管弹性好,内膜表面平滑,富有光泽;高脂模型组动脉弹性减低,管壁增厚,内膜面光泽度稍差;通心络胶囊组及通络汤各治疗组与正常组相比变化不明显。5.2光镜观察:正常组动脉内膜光滑,EC排列整齐、无缺失,内膜下间隙较小;高脂模型组血管壁增厚,内膜不光滑,EC呈连续性缺失,底层胶原纤维暴露,大量MC粘附于内皮表面或潜入内皮下,内皮下间隙增宽;通络汤低剂量组组内膜较光滑,局部有少量MC粘附,可见EC缺失,但明显好于模型组;通心络胶囊组及通络汤中、高剂量组与正常组相比未见明显差别。
结论
本实验成功复制Wistar大鼠食饵性高脂血症及早期AS病变模型,通络汤用药后,观察大鼠血脂浓度、血清NO、血浆血栓素B_2(TXB_2)、6-Keto-PGF_(1α)水平及形态变化。结果表明:
1、通络汤可调节高脂血症大鼠的脂代谢紊乱,降低TC、TG、LDL,升高HDL;
2、通络汤可改善EC功能,增强NO活性;
3、通络汤能够显著降低高血脂大鼠血浆中血栓素A_2的量,升高PGI_2,降低TXA_2/PGI_2的比值,能明显改善两者平衡。
4、形态学观察发现(肉眼、光镜)能保护血管EC,通络汤减轻AS早期EC受损的程度。
Objective
Atherosclerosis is a chronic arterial disease,and the majority patients is the aged. Atherosclerosis is one of the most prevalent fatal diseases which can lead to various diseases such as coronary heart disease,angina pectoris,cardiac muscle infarction, cerebral embolism,cerebral hemorrhage,encephalanalosis,dementia.Tong luo soup was used in clinical and have got good effect which can supplement qi and tenify kidney,activate blood circulation and clear the channels.The present experiment is to study the effect of Tong luo soup on serum level and aortic morphology in early atherosclerosis rats fed by high fat diet and its possible mechanism.
Methods
Sixty Wister rats were randomly and equally divided into six groups:normal group,model group,Tongxinluo Capsules group,Tongluo low dose group,Tongluo middle dose group,Tongluo high dose group.Normal saline was given to rats of normal group and model group at the same volume and same way.The normal group was fed with standard chow,other groups were fed with high lipid diet.The serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),nitric oxide(NO),6-Keto-PGF_1αand TXB2 were measured after eight weeks.Morphological changes of aorta were observed under gross and light microscopes.
Results
1.In model group,TC and TG and LDL were increased and HDL was decreased compared with normal group(P＜0.01).After treating with Tongluo soup,TC and TG and LDL were decreased compared with model group(P＜0.01),and HDL were increased compared with model group(P＜0.01).
2.The content of NO was higher in model group compared with the normal group(p＜0.01).The low dosage equisetum increased the bioactivity of NOS,decrease the release of NO.
3.In model group,the contents of 6-keto-prostacyclin lalpha(6-keto-PGF1α) was lower and thromboxane B2(TXB2)was higher compared with the normal group(p＜0.01).After treating with Tongluo soup,6-keto-PGF_1αwas decreased compared with model group(P＜0.01),and TXB_2 was increased compared with model group(P＜0.01).
4.We found the changes of the early stage of atherosclerosis in model group:There were focal or transient areas of endothelium loss,monoeyte adhered to the subendothelial space or moved into the vascular wall,et al.Those changes of aorta endothelium in fed Tongluo soup animals were less compared with model group.
Conclusion
1.Tongluo soup has obvious effect on decreasing the serum levels of TC and TG and LDL,and increasing the serum level of HDL in atherosclerotie rats.
2.Tongluo soup can regulate the release of NO.
3.Tongluo soup can significantly reduce thromboxane A2 and increased PGI2.
4.Morphological changes of aorta were showed a significant effect of protecting aorta endothelial cell in rats fed with Tongluo soup.
动脉粥样硬化是一种慢性的动脉疾病,发病人群以老年人居多。动脉粥样硬化可导致冠心病、心绞痛、心肌梗死、脑血栓、脑出血、脑萎缩、痴呆等多种疾病,严重危害人类的健康。通络汤具有益气补肾、活血通络的功效,用于临床效果较好。为了进一步研究其对动脉硬化的早期防治作用,本实验观察了通络汤对动脉粥样硬化(As)大鼠的作用效果,并探讨其抗As的可能作用机制。
方法
SPF级纯种Wistar大鼠60只,雌雄各半,体重170±20g,随机分成6组,每组10只。即正常对照组、高脂饲料组、通心络胶囊组、通络汤低、中、高剂量组。在造模过程中即开始给药。通络汤浓缩液(由黄石市中医院提供,常规煎煮):高浓度2.7g/ml、中浓度1.35g/ml、低浓度0.675g/ml;通心络胶囊配置成混悬液,浓度为2.05%。上述各组均按1ml/100g体重的剂量于每日早8时灌胃,每日一次。连续给药10周后,禁食12小时,断头取血,检测大鼠血脂浓度、血清NO、血浆血栓素B_2(TXB_2)、6-Keto-PGF_(1α)水平,并取主动脉作病理学检查。
结果
1、一般指标的变化
正常组大鼠毛色光泽,活动自如,反应灵敏,饮食正常。高脂饲料组体重增长较快,皮下脂肪厚,但随实验进程,毛发色泽暗淡,活动减少,反应迟钝,精神状态较差,进食量减少。通心络胶囊组较对照组活动稍有减少、反应尚灵敏、皮毛光泽、进食量稍有减少。通络汤高、中剂量组活动稍有减少,反应灵敏,皮毛尚光泽,食欲稍有减退。通络汤低剂量组活动减少,反应欠灵敏,皮毛色泽暗淡,食欲减退。
2、TC、TG、LDL、HDL的变化
高脂饲料组TC、TG、LDL较正常对照组明显升高(p＜0.01),HDL降低(p＜0.01);通心络胶囊组及通络汤各剂量组总TC、TG、LDL较高脂饲料组显著降低(p＜0.01),而HDL升高(p＜0.01)。通络汤高剂量组与通心络胶囊组相比无差别。
3、血清NO的变化
高脂饲料组NO浓度较正常对照组显著降低(p＜0.01)。通心络胶囊组、通络汤中、高剂量组NO显著升高(p＜0.01)。通络汤中、高剂量组与通心络胶囊组相比无差别。
4、血浆6-Keto-PGF_1α和TXB_2的变化
高脂饲料组血浆6-Keto-PGF_1α水平较正常组显著降低,TCB_2、TXB_2/PGF_(1α)显著升高(p＜0.01);通络汤各剂量组血浆6-Keto-PGF_(1α)水平较高脂组均显著升高(p＜0.01),通心络胶囊组及通络汤各剂量组血浆TXB_2,TXB_2/PGF_1α的水平均显著降低(p＜0.01);通络汤各剂量组血浆6-Keto-PGF_(1α)水平较通心络胶囊组均有显著差别,中、高剂量组血浆TXB_2水平无显著差别,各剂量组TXB_2/PGF_(1α)的水平无显著差别。
5、胸主动脉形态学改变
5.1肉眼观察:正常组血管弹性好,内膜表面平滑,富有光泽;高脂模型组动脉弹性减低,管壁增厚,内膜面光泽度稍差;通心络胶囊组及通络汤各治疗组与正常组相比变化不明显。5.2光镜观察:正常组动脉内膜光滑,EC排列整齐、无缺失,内膜下间隙较小;高脂模型组血管壁增厚,内膜不光滑,EC呈连续性缺失,底层胶原纤维暴露,大量MC粘附于内皮表面或潜入内皮下,内皮下间隙增宽;通络汤低剂量组组内膜较光滑,局部有少量MC粘附,可见EC缺失,但明显好于模型组;通心络胶囊组及通络汤中、高剂量组与正常组相比未见明显差别。
结论
本实验成功复制Wistar大鼠食饵性高脂血症及早期AS病变模型,通络汤用药后,观察大鼠血脂浓度、血清NO、血浆血栓素B_2(TXB_2)、6-Keto-PGF_(1α)水平及形态变化。结果表明:
1、通络汤可调节高脂血症大鼠的脂代谢紊乱,降低TC、TG、LDL,升高HDL;
2、通络汤可改善EC功能,增强NO活性;
3、通络汤能够显著降低高血脂大鼠血浆中血栓素A_2的量,升高PGI_2,降低TXA_2/PGI_2的比值,能明显改善两者平衡。
4、形态学观察发现(肉眼、光镜)能保护血管EC,通络汤减轻AS早期EC受损的程度。
Objective
Atherosclerosis is a chronic arterial disease,and the majority patients is the aged. Atherosclerosis is one of the most prevalent fatal diseases which can lead to various diseases such as coronary heart disease,angina pectoris,cardiac muscle infarction, cerebral embolism,cerebral hemorrhage,encephalanalosis,dementia.Tong luo soup was used in clinical and have got good effect which can supplement qi and tenify kidney,activate blood circulation and clear the channels.The present experiment is to study the effect of Tong luo soup on serum level and aortic morphology in early atherosclerosis rats fed by high fat diet and its possible mechanism.
Methods
Sixty Wister rats were randomly and equally divided into six groups:normal group,model group,Tongxinluo Capsules group,Tongluo low dose group,Tongluo middle dose group,Tongluo high dose group.Normal saline was given to rats of normal group and model group at the same volume and same way.The normal group was fed with standard chow,other groups were fed with high lipid diet.The serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),nitric oxide(NO),6-Keto-PGF_1αand TXB2 were measured after eight weeks.Morphological changes of aorta were observed under gross and light microscopes.
Results
1.In model group,TC and TG and LDL were increased and HDL was decreased compared with normal group(P＜0.01).After treating with Tongluo soup,TC and TG and LDL were decreased compared with model group(P＜0.01),and HDL were increased compared with model group(P＜0.01).
2.The content of NO was higher in model group compared with the normal group(p＜0.01).The low dosage equisetum increased the bioactivity of NOS,decrease the release of NO.
3.In model group,the contents of 6-keto-prostacyclin lalpha(6-keto-PGF1α) was lower and thromboxane B2(TXB2)was higher compared with the normal group(p＜0.01).After treating with Tongluo soup,6-keto-PGF_1αwas decreased compared with model group(P＜0.01),and TXB_2 was increased compared with model group(P＜0.01).
4.We found the changes of the early stage of atherosclerosis in model group:There were focal or transient areas of endothelium loss,monoeyte adhered to the subendothelial space or moved into the vascular wall,et al.Those changes of aorta endothelium in fed Tongluo soup animals were less compared with model group.
Conclusion
1.Tongluo soup has obvious effect on decreasing the serum levels of TC and TG and LDL,and increasing the serum level of HDL in atherosclerotie rats.
2.Tongluo soup can regulate the release of NO.
3.Tongluo soup can significantly reduce thromboxane A2 and increased PGI2.
4.Morphological changes of aorta were showed a significant effect of protecting aorta endothelial cell in rats fed with Tongluo soup.
引文
[1]郭延松,杨军坷.鼠动脉粥样硬化模型的建立[J].中国动脉硬化杂志,2003;11(1):84-85
[2]Fleckenstein KN,Kehel L,Bouayadi FE,oral.New mldelof atheroscleros is in insulin resistant sand rats hypercholeste rolemia combined with D_2vitam ink[J].Atherasclerasis,2000;150:55-61
[3]Price PA,Faus SA,W illiam son MK.W arfarin-induced artery calc ificalion is accelerated by growth andvitam in D[J].Atherosclerosis Thromb Vasc Biol,2000;20:317-323
[4]温进坤,韩梅,杜玮南,等.一种快速建立人鼠动脉粥样硬化模型的方法[J].中国老年学杂志,2001:21:50-52
[5]Price PA,June HH,Buekley JR,etal.Osteoproteger in inhibits artery calcigfication induced by warfarin and by vitam in D[J].Arterio-scler Thromb Vase Bio,2001;21:1610-1616
[6]杨鹏远,丙耀诚.动脉粥样硬化大鼠实验模型的建立[J].第二军医大学学报,2003:24(7):802-804
[7]Bennani KN,Kehel L,Bouayadi F,etal.New model of atheroscle-rosis in sand rats subjected to a high cholesterol diet and vitam in D_2[J].Therapie,1999;54:559-565.
[8]Furchgott RF,Zawadzki JV.The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.[J]Nature,1980(89):288,373-376.
[9]Park IB,Charbonneau F,Schiffrin EL.Correlation of endothelial function in large and small arteries in human essential hypertension[J].J Hyperten,2001;19(3):415-420.
[10]Levy RM,Prince JM,Billiar TR.Nitric oxide:a clinical primer Crit Care Med,2005;33:492-495.
[11]Jan M s,Lee Y J,Shin S J,et al.oxidied lowdensity lipoprotein sitimulates endothelin-1 and mRNA expression from rat mesangial cells [J].J-Lab-Clin-Med,1997;129(2):224-230.
[12]John R Vane.F.R.S.D,Sc Enik E.Betting phd regulatory functions of the vascalar endothelium[J].The New England Journal Medicine,1998;(323):27-35.
[13]Jones G T,Van A M,Soloman C,etal.Endothelin-1 is increased overlying atherosclerotic plaques in human arteries[J].Atherosclerosis,1996;124(1):25-35
[14]Lerman A,edwards B S,Hallett J W,et al.Circulation and tissue endothlin immunoreacyivity in advance atherosclerosis[J].N Engl J Mde,1991;325:997-1001
[15]宋良文,王雪青,张静文,等.氧化低低密度脂蛋白与内皮素在促进血管平滑肌细胞增生中的内在联系[J].中国动脉硬化杂志,1994;2(2-3):84-86
[16]Mikhail G,Chester AH,Gibbs JS,et al.Role of vasoactive mediators in primary and secondary pulmonary hypertension[J].Am J Cardiol,1998;82(2):254-255
[17]Shakhmalova M Sh,Shetakova M V,Chugunova LA,et al.Vasoactive factors of the vascular endothelium in patients with non-insulin-dependent diabetes mellitus and kidney involvement[J].Ter Arkh,1996;68(6):43-6
[18]赵铁军.血管内皮功能障碍及其治疗进展[J].国外医学心血管疾病分册,1999;26(2):70-73
[19]樊燕蓉,陈进贵,薛龙增,等.L-arg对高胆固醇血症兔血管血管反应性的影响[J].心肺血管病杂志,1999;18(1):63-66
[20]苑利伟,李元建.内源性一氧化氮合酶抑制物与心血管疾病[J].中国动脉硬化杂志,1998;6(3):264-265
[21]暴宪斌,沈俊兰.黄芪的药理作用及临床研究进展[J].山西中医,2006;(22):6:48-49
[22]武敬亮,苏智先,田桂香,等.淫羊藿研究新进展[J].中医药学报,2004;32(3):69-72
[23]盛军利,孙桂菊.杜仲的功效学研究现状及其应用前景[J].医学综述,2006;12(16):1022-1024
[24]崔哲.丹参的药理作用与临床应用[J].现代医药卫生,2007;23(21):3239-3240
[25]周江.川芎有效成分及其药理作用研究概况[J].浙江中医杂志,2007;10(42):615-616
[26]欧仕益,包惠燕,蓝志东.阿魏酸及其衍生物的药理作用研究进展[J].中药材,2001;(8):220-221.
[27]谢玲,杨凌红,李晓惠.当归药理作用研究进展[J].中医药研究.2000;12(16):56-58
[28]木海鸥.地龙的药理研究概要[J].中国药业,2007;(1):61
[29]吴启端,吴清和.石葛蒲的药理研究进展[J],中药新药与临床药理,2006;11(7):477-480
[1]丁志山,沃兴德.姜黄降血脂抗动脉粥样硬化研究概况[J].浙江中医学院学报,1998;22(6):8.
[2]汪德清,丁保国,Tomas G Neil,等.黄芪总黄酮对动脉粥样硬化早期形成的影响[J].中国药理学通报,2003;19(6):637.
[3]戴敏,訾晓梅,彭代银,等.丹皮酚抗鹌鹑实验性动脉粥样硬化作用[J].中国中药杂志,1999;24(8):488.
[4]黄河清,吴伟康,程超,等.四逆汤抗实验性动脉粥样硬化的作用及其机制[J].中国动脉硬化杂志,2000;8(4):302-304.
[5]聂松柳,徐先祥,夏伦祝,等.党参总皂甙对实验性高脂血症大鼠血脂和NO含量的影响[J].安徽中医学院学报,2002;21(4):40-42.
[6]庞战军等.云芝多糖对小鼠腹腔巨噬细胞锰超氧化物歧化酶基因表达的调控[J].中国动脉硬化杂志,1999;7(2):106.
[7]刘红.丹参对动脉粥样硬化家兔血清一氧化氮、血浆内皮素和脂质过氧化物的影响[J].湖北中医杂志,2001;23(8):11.
[8]陈成川,杨宏杰,陈士明,等.单味当归抑制低密度脂蛋白氧化的方法研究和临床观察[J].上海中医药大学学报,2001;15(4):25.
[9]李淑莲,张永雪,林波,等.杏仁对家兔动脉粥样硬化及金属硫蛋白含量的影响[J].河南大学学报(医学科学版),2002;21(4):16.
[10]郑勇英,杨隽,潘喜华,等.银杏叶抗衰老和调节血脂的实验研究[J].上海预防医学杂志,2000;12(2):71.
[11]陈临溪,王蓉蓉,黄红林,等.银杏叶提取物对饲高胆固醇兔动脉粥样硬化和低密度脂蛋白体外氧化的作用[J].心肺血管病杂志,2001;20(1):46.
[12]黄河清,刘培庆,黄民.抵当汤改良方抗家兔实验性动脉粥样硬化效应及机制初探[J].中国药理学通报 2003;19(5):590.
[13]黄河清,吴伟康,罗汉川.四逆汤与维生素E抗血管内皮功能氧化损伤及防治家兔实验性动脉粥样硬化的比较研究[J].中国病理生理杂志,2001;17(2):154.
[14]刘发益等.补阳还五汤抗家兔动脉粥样硬化形成的实验研究[J].湖南医科大学学报,2000;25(1):35.
[15]SekiyaN,KainumaM,HikiamiH,etal.Oren2gedoku2tandKeishi2bukuryo2gan 2ryolnhibittheProgressionoAtherosclerosisinDiet2InducedHypercholester olemicRabbit[J].BiolPharmBull,2005;28(2):294-298.
[16]王利津,徐强.黄连解毒汤的抗炎作用机理研究[J].中国中药杂志,2000;25(8):493-496.
[17]WangLM,MineshitaS.Preventiveeffectsofunsei2inandoren2gedoku2to,Ch inesetraditionalmedicines,againstratpawoedemaandabdominalconstriction inmice[J].JpharmPharmacol,1996;48(3):327-31.
[18]LiuF,NgTB.Antioxidativeandfreeradicalscavengingactivitiesofselect edmedicinalherbs[J].LifeSci,2000;66(8):725-735.
[19]张红霞,刘剑刚,马鲁波,等.气血并治方及方中理气药、活血药对高脂血症血瘀大鼠炎症因子的干预作用[J].北京中医药大学学报,2004;27(4):27-30.
[20]刘宇,顾仁樾,周瑞.白蒺藜有效组分对兔动脉粥样硬化斑块和主动脉壁血小板源性生长因子-A基因表达的影响[J].中国中医基础医学杂志,2001;7(8):14-17.
[21]胡发明,胡红丁.川芎嗪的实验研究及临床应用[J].中医研究,2004;17(3):57.
[22]王军跃.芪棱片对实验性动脉粥样硬化家兔血液流变学的影响[J].中国中医基础医学杂志,1999;5:(7):21.
[23]孙敬昌,闫滨,赵启韬,等.黄芪通脉汤抗动脉粥样硬化实验研究[J].山东中医药大学学报,2001;25(4):302.
[24]汪海娅,陆惠华,方宁远,等.益气活血方对动脉粥样硬化模型兔血脂及动脉结构的影响[J].老年医学与保健,2000;6(4):174-176.
[25]陆一竹,范英昌,任学军.调肝导浊中药防治家兔动脉粥样硬化病变形成的实验研究[J].中国药学报,2002;17(9):532-533.
[26]Delerive P.Martin-Nizard-F Am J Physiol,1999,276(32):11-12.
[27]Orlov SN,Dam TV,Trembly J,et al.Biochemistry Bio-physics Commun, 1996;221(3):708-715.
[28]周晓霞,苏佩清,杨鹤梅,等.三七总皂甙对人高脂血清诱发的胎儿血管平滑肌细胞增殖的抑制作用[J].中国动脉硬化杂志,2000;8(1):43.
[29]刘永平,周晓霞,许倩.黄芩茎叶总黄酮对高脂血清刺激的平滑肌细胞增殖的抑制作用[J].中国全科医学杂志,2000;3(1):28.
[30]庞荣清,潘兴华,龙沛然,等.灯盏花素对兔血管平滑肌细胞增殖的影响[J].中国动脉硬化杂志[J].2004;12(4):395-398.
[31]王敏,崔连群,张承俊,等.水蛭素对凝血酶诱导的血管平滑肌细胞增殖的影响[J].中国动脉硬化杂志.2003;11(7):609-612.
[32]万迎新,张铁忠.通脉益智胶囊对动脉粥样硬化家兔大脑中动脉的影响[J].北京中医药大学学报 2004;27(1):39-41.
[33]李浩,刘芳,崔玲,等.降压胶囊对老年单纯收缩期高血压血清一氧化氮合酶活性、丙二醛水平及血浆神经肤Y、同型半耽氨酸浓度的影响[J].中国中西医结合杂志,2003;23(12),898-901.
[34]刘贵京,高红旗,呼金田,等.山楂对高血压病患者血浆同型半脆氮酸含量的影响[J].中国全科医学,2003;6(4),295-296.
[35]PACIFIC Study Group.Dose-dependent effects of relic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease[J].Eur Heart J,2002;23(19):1509-1515.
[36]Schnyder G,Roffi M,Flammer Y,et al.Association of plasma homocysteine wity restenosis after percutaneous coronary angioplasty [J].Eur Heart J,2002;23(9):726-733.
[37]李凤文,刘晓颖,张立石,等.水蛭及其复方对实验性动脉粥样硬化家兔主动脉内皮素基因表达的影响[J].中医杂志.1999;1(40):50-51
[38]李亚俊,宋剑南,周瑕箐等.脂泰胶囊对实验性动脉粥样硬化家兔内皮素及一氧化氮合酶基因表达的影响[J].中国动脉硬化杂志.1999;7(1):4-8.
[39]吕燕宁等.葛根素对血管平滑肌细胞凋亡及其相关基因表达的影响[J].中华临床医药杂志,2002;3(1):9-12
[40]王亚利,司秋菊,王鑫国,等.蜈蚣对动脉粥样硬化家兔血管平滑肌细胞周期 及c-myc基因表达的影响[J].中药药理与临床,2001;17(6):28
[41]贺兰萍,高建英,昌艳艳,等.穿心莲对兔胸主动脉内膜损伤后血管内皮细胞中PDGF-B蛋白的表达影响[J].中国老年学杂志,2005;(02).
[42]王宏伟,赵华月,熊一力,等.穿心莲提出物对动脉粥样硬化家兔动脉壁PDGF-B、C-sis和c-myc基因表达的影响[J].华中科技大学学报(医学版),1998;2(27):46-18
[43]于永红,胡昌兴,孟卫星,等.茵陈、赤芍、三棱、淫羊藿对家兔实验性动脉粥样硬化病灶的消退作用及原癌基因C-myc、C-fos、V-sis表达的影响[J].湖北民族学院学报·医学版·2001;18(2):4-7.
[44]姜传仓,蔡海江,范乐明,等.丹参对LDL受体及apoA-ImRNA水平的影响[J].1994,14(4):522-524
[45]李文彪,王毅仁.清源调脂胶囊对高脂血症大鼠低密度脂蛋白受体基因表达的影响[J].中国动脉硬化杂志,2002;22(4):327-329.
[46]韩峰,谢海林,朱路佳,等.白草降脂灵对AS兔Ox-LDL及LDL-R-mRNA表达的影响[J].中国新药与临床,2002;21(7):389-391.
[47]胡霞敏,周密妹,胡先敏,等.丹参酮11A预防性给药对脑缺血/再灌注损伤炎症反应的影响[J].中国药理学通报,2006;22(4):436-440.
[48]王哲,高聆.丹参对实验糖尿病大鼠粘附分子CD54、CD106、CD62p的影响[J].中国药物与临床,2002;2(5):286-288.
[49]周俊琴,刘敏,夏先明,等.芪丹煎对动脉粥样硬化家兔血管细胞黏附分子-1蛋白表达的影响[J].北京中医药大学学报.2004;27(5)42-44.
[50]刘宇,顾仁樾,周端,等.白蒺藜有效组分对兔动脉粥样硬化和主动脉壁血小板源性生长因子A基因表达影响[J].中国中医基础医学杂志 2001;7(8):574
[51]王会玲等.中药双龙丸对血管平滑肌细胞、血小板衍化生长因子-A及单核细胞趋化蛋白-mRNA表达的影响[J].中国中西医结合杂志.2000;20(8):612-615.
[2]Fleckenstein KN,Kehel L,Bouayadi FE,oral.New mldelof atheroscleros is in insulin resistant sand rats hypercholeste rolemia combined with D_2vitam ink[J].Atherasclerasis,2000;150:55-61
[3]Price PA,Faus SA,W illiam son MK.W arfarin-induced artery calc ificalion is accelerated by growth andvitam in D[J].Atherosclerosis Thromb Vasc Biol,2000;20:317-323
[4]温进坤,韩梅,杜玮南,等.一种快速建立人鼠动脉粥样硬化模型的方法[J].中国老年学杂志,2001:21:50-52
[5]Price PA,June HH,Buekley JR,etal.Osteoproteger in inhibits artery calcigfication induced by warfarin and by vitam in D[J].Arterio-scler Thromb Vase Bio,2001;21:1610-1616
[6]杨鹏远,丙耀诚.动脉粥样硬化大鼠实验模型的建立[J].第二军医大学学报,2003:24(7):802-804
[7]Bennani KN,Kehel L,Bouayadi F,etal.New model of atheroscle-rosis in sand rats subjected to a high cholesterol diet and vitam in D_2[J].Therapie,1999;54:559-565.
[8]Furchgott RF,Zawadzki JV.The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.[J]Nature,1980(89):288,373-376.
[9]Park IB,Charbonneau F,Schiffrin EL.Correlation of endothelial function in large and small arteries in human essential hypertension[J].J Hyperten,2001;19(3):415-420.
[10]Levy RM,Prince JM,Billiar TR.Nitric oxide:a clinical primer Crit Care Med,2005;33:492-495.
[11]Jan M s,Lee Y J,Shin S J,et al.oxidied lowdensity lipoprotein sitimulates endothelin-1 and mRNA expression from rat mesangial cells [J].J-Lab-Clin-Med,1997;129(2):224-230.
[12]John R Vane.F.R.S.D,Sc Enik E.Betting phd regulatory functions of the vascalar endothelium[J].The New England Journal Medicine,1998;(323):27-35.
[13]Jones G T,Van A M,Soloman C,etal.Endothelin-1 is increased overlying atherosclerotic plaques in human arteries[J].Atherosclerosis,1996;124(1):25-35
[14]Lerman A,edwards B S,Hallett J W,et al.Circulation and tissue endothlin immunoreacyivity in advance atherosclerosis[J].N Engl J Mde,1991;325:997-1001
[15]宋良文,王雪青,张静文,等.氧化低低密度脂蛋白与内皮素在促进血管平滑肌细胞增生中的内在联系[J].中国动脉硬化杂志,1994;2(2-3):84-86
[16]Mikhail G,Chester AH,Gibbs JS,et al.Role of vasoactive mediators in primary and secondary pulmonary hypertension[J].Am J Cardiol,1998;82(2):254-255
[17]Shakhmalova M Sh,Shetakova M V,Chugunova LA,et al.Vasoactive factors of the vascular endothelium in patients with non-insulin-dependent diabetes mellitus and kidney involvement[J].Ter Arkh,1996;68(6):43-6
[18]赵铁军.血管内皮功能障碍及其治疗进展[J].国外医学心血管疾病分册,1999;26(2):70-73
[19]樊燕蓉,陈进贵,薛龙增,等.L-arg对高胆固醇血症兔血管血管反应性的影响[J].心肺血管病杂志,1999;18(1):63-66
[20]苑利伟,李元建.内源性一氧化氮合酶抑制物与心血管疾病[J].中国动脉硬化杂志,1998;6(3):264-265
[21]暴宪斌,沈俊兰.黄芪的药理作用及临床研究进展[J].山西中医,2006;(22):6:48-49
[22]武敬亮,苏智先,田桂香,等.淫羊藿研究新进展[J].中医药学报,2004;32(3):69-72
[23]盛军利,孙桂菊.杜仲的功效学研究现状及其应用前景[J].医学综述,2006;12(16):1022-1024
[24]崔哲.丹参的药理作用与临床应用[J].现代医药卫生,2007;23(21):3239-3240
[25]周江.川芎有效成分及其药理作用研究概况[J].浙江中医杂志,2007;10(42):615-616
[26]欧仕益,包惠燕,蓝志东.阿魏酸及其衍生物的药理作用研究进展[J].中药材,2001;(8):220-221.
[27]谢玲,杨凌红,李晓惠.当归药理作用研究进展[J].中医药研究.2000;12(16):56-58
[28]木海鸥.地龙的药理研究概要[J].中国药业,2007;(1):61
[29]吴启端,吴清和.石葛蒲的药理研究进展[J],中药新药与临床药理,2006;11(7):477-480
[1]丁志山,沃兴德.姜黄降血脂抗动脉粥样硬化研究概况[J].浙江中医学院学报,1998;22(6):8.
[2]汪德清,丁保国,Tomas G Neil,等.黄芪总黄酮对动脉粥样硬化早期形成的影响[J].中国药理学通报,2003;19(6):637.
[3]戴敏,訾晓梅,彭代银,等.丹皮酚抗鹌鹑实验性动脉粥样硬化作用[J].中国中药杂志,1999;24(8):488.
[4]黄河清,吴伟康,程超,等.四逆汤抗实验性动脉粥样硬化的作用及其机制[J].中国动脉硬化杂志,2000;8(4):302-304.
[5]聂松柳,徐先祥,夏伦祝,等.党参总皂甙对实验性高脂血症大鼠血脂和NO含量的影响[J].安徽中医学院学报,2002;21(4):40-42.
[6]庞战军等.云芝多糖对小鼠腹腔巨噬细胞锰超氧化物歧化酶基因表达的调控[J].中国动脉硬化杂志,1999;7(2):106.
[7]刘红.丹参对动脉粥样硬化家兔血清一氧化氮、血浆内皮素和脂质过氧化物的影响[J].湖北中医杂志,2001;23(8):11.
[8]陈成川,杨宏杰,陈士明,等.单味当归抑制低密度脂蛋白氧化的方法研究和临床观察[J].上海中医药大学学报,2001;15(4):25.
[9]李淑莲,张永雪,林波,等.杏仁对家兔动脉粥样硬化及金属硫蛋白含量的影响[J].河南大学学报(医学科学版),2002;21(4):16.
[10]郑勇英,杨隽,潘喜华,等.银杏叶抗衰老和调节血脂的实验研究[J].上海预防医学杂志,2000;12(2):71.
[11]陈临溪,王蓉蓉,黄红林,等.银杏叶提取物对饲高胆固醇兔动脉粥样硬化和低密度脂蛋白体外氧化的作用[J].心肺血管病杂志,2001;20(1):46.
[12]黄河清,刘培庆,黄民.抵当汤改良方抗家兔实验性动脉粥样硬化效应及机制初探[J].中国药理学通报 2003;19(5):590.
[13]黄河清,吴伟康,罗汉川.四逆汤与维生素E抗血管内皮功能氧化损伤及防治家兔实验性动脉粥样硬化的比较研究[J].中国病理生理杂志,2001;17(2):154.
[14]刘发益等.补阳还五汤抗家兔动脉粥样硬化形成的实验研究[J].湖南医科大学学报,2000;25(1):35.
[15]SekiyaN,KainumaM,HikiamiH,etal.Oren2gedoku2tandKeishi2bukuryo2gan 2ryolnhibittheProgressionoAtherosclerosisinDiet2InducedHypercholester olemicRabbit[J].BiolPharmBull,2005;28(2):294-298.
[16]王利津,徐强.黄连解毒汤的抗炎作用机理研究[J].中国中药杂志,2000;25(8):493-496.
[17]WangLM,MineshitaS.Preventiveeffectsofunsei2inandoren2gedoku2to,Ch inesetraditionalmedicines,againstratpawoedemaandabdominalconstriction inmice[J].JpharmPharmacol,1996;48(3):327-31.
[18]LiuF,NgTB.Antioxidativeandfreeradicalscavengingactivitiesofselect edmedicinalherbs[J].LifeSci,2000;66(8):725-735.
[19]张红霞,刘剑刚,马鲁波,等.气血并治方及方中理气药、活血药对高脂血症血瘀大鼠炎症因子的干预作用[J].北京中医药大学学报,2004;27(4):27-30.
[20]刘宇,顾仁樾,周瑞.白蒺藜有效组分对兔动脉粥样硬化斑块和主动脉壁血小板源性生长因子-A基因表达的影响[J].中国中医基础医学杂志,2001;7(8):14-17.
[21]胡发明,胡红丁.川芎嗪的实验研究及临床应用[J].中医研究,2004;17(3):57.
[22]王军跃.芪棱片对实验性动脉粥样硬化家兔血液流变学的影响[J].中国中医基础医学杂志,1999;5:(7):21.
[23]孙敬昌,闫滨,赵启韬,等.黄芪通脉汤抗动脉粥样硬化实验研究[J].山东中医药大学学报,2001;25(4):302.
[24]汪海娅,陆惠华,方宁远,等.益气活血方对动脉粥样硬化模型兔血脂及动脉结构的影响[J].老年医学与保健,2000;6(4):174-176.
[25]陆一竹,范英昌,任学军.调肝导浊中药防治家兔动脉粥样硬化病变形成的实验研究[J].中国药学报,2002;17(9):532-533.
[26]Delerive P.Martin-Nizard-F Am J Physiol,1999,276(32):11-12.
[27]Orlov SN,Dam TV,Trembly J,et al.Biochemistry Bio-physics Commun, 1996;221(3):708-715.
[28]周晓霞,苏佩清,杨鹤梅,等.三七总皂甙对人高脂血清诱发的胎儿血管平滑肌细胞增殖的抑制作用[J].中国动脉硬化杂志,2000;8(1):43.
[29]刘永平,周晓霞,许倩.黄芩茎叶总黄酮对高脂血清刺激的平滑肌细胞增殖的抑制作用[J].中国全科医学杂志,2000;3(1):28.
[30]庞荣清,潘兴华,龙沛然,等.灯盏花素对兔血管平滑肌细胞增殖的影响[J].中国动脉硬化杂志[J].2004;12(4):395-398.
[31]王敏,崔连群,张承俊,等.水蛭素对凝血酶诱导的血管平滑肌细胞增殖的影响[J].中国动脉硬化杂志.2003;11(7):609-612.
[32]万迎新,张铁忠.通脉益智胶囊对动脉粥样硬化家兔大脑中动脉的影响[J].北京中医药大学学报 2004;27(1):39-41.
[33]李浩,刘芳,崔玲,等.降压胶囊对老年单纯收缩期高血压血清一氧化氮合酶活性、丙二醛水平及血浆神经肤Y、同型半耽氨酸浓度的影响[J].中国中西医结合杂志,2003;23(12),898-901.
[34]刘贵京,高红旗,呼金田,等.山楂对高血压病患者血浆同型半脆氮酸含量的影响[J].中国全科医学,2003;6(4),295-296.
[35]PACIFIC Study Group.Dose-dependent effects of relic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease[J].Eur Heart J,2002;23(19):1509-1515.
[36]Schnyder G,Roffi M,Flammer Y,et al.Association of plasma homocysteine wity restenosis after percutaneous coronary angioplasty [J].Eur Heart J,2002;23(9):726-733.
[37]李凤文,刘晓颖,张立石,等.水蛭及其复方对实验性动脉粥样硬化家兔主动脉内皮素基因表达的影响[J].中医杂志.1999;1(40):50-51
[38]李亚俊,宋剑南,周瑕箐等.脂泰胶囊对实验性动脉粥样硬化家兔内皮素及一氧化氮合酶基因表达的影响[J].中国动脉硬化杂志.1999;7(1):4-8.
[39]吕燕宁等.葛根素对血管平滑肌细胞凋亡及其相关基因表达的影响[J].中华临床医药杂志,2002;3(1):9-12
[40]王亚利,司秋菊,王鑫国,等.蜈蚣对动脉粥样硬化家兔血管平滑肌细胞周期 及c-myc基因表达的影响[J].中药药理与临床,2001;17(6):28
[41]贺兰萍,高建英,昌艳艳,等.穿心莲对兔胸主动脉内膜损伤后血管内皮细胞中PDGF-B蛋白的表达影响[J].中国老年学杂志,2005;(02).
[42]王宏伟,赵华月,熊一力,等.穿心莲提出物对动脉粥样硬化家兔动脉壁PDGF-B、C-sis和c-myc基因表达的影响[J].华中科技大学学报(医学版),1998;2(27):46-18
[43]于永红,胡昌兴,孟卫星,等.茵陈、赤芍、三棱、淫羊藿对家兔实验性动脉粥样硬化病灶的消退作用及原癌基因C-myc、C-fos、V-sis表达的影响[J].湖北民族学院学报·医学版·2001;18(2):4-7.
[44]姜传仓,蔡海江,范乐明,等.丹参对LDL受体及apoA-ImRNA水平的影响[J].1994,14(4):522-524
[45]李文彪,王毅仁.清源调脂胶囊对高脂血症大鼠低密度脂蛋白受体基因表达的影响[J].中国动脉硬化杂志,2002;22(4):327-329.
[46]韩峰,谢海林,朱路佳,等.白草降脂灵对AS兔Ox-LDL及LDL-R-mRNA表达的影响[J].中国新药与临床,2002;21(7):389-391.
[47]胡霞敏,周密妹,胡先敏,等.丹参酮11A预防性给药对脑缺血/再灌注损伤炎症反应的影响[J].中国药理学通报,2006;22(4):436-440.
[48]王哲,高聆.丹参对实验糖尿病大鼠粘附分子CD54、CD106、CD62p的影响[J].中国药物与临床,2002;2(5):286-288.
[49]周俊琴,刘敏,夏先明,等.芪丹煎对动脉粥样硬化家兔血管细胞黏附分子-1蛋白表达的影响[J].北京中医药大学学报.2004;27(5)42-44.
[50]刘宇,顾仁樾,周端,等.白蒺藜有效组分对兔动脉粥样硬化和主动脉壁血小板源性生长因子A基因表达影响[J].中国中医基础医学杂志 2001;7(8):574
[51]王会玲等.中药双龙丸对血管平滑肌细胞、血小板衍化生长因子-A及单核细胞趋化蛋白-mRNA表达的影响[J].中国中西医结合杂志.2000;20(8):612-615.