血浆尾加压素Ⅱ水平在相关疾病中变化的临床和基础研究
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摘要
在很多心血管疾病中,血管平滑肌细胞(vascular smooth muscle cell,VSMC)的增殖及凋亡是其共同病理基础,因此有关VSMC增殖及凋亡的研究已经成为心血管疾病防治研究的热点。尾加压素Ⅱ(urotensinⅡ,UⅡ)是目前已知的最强的缩血管活性物质,且对多系统具有复杂的生理效应。本研究主要探讨心血管疾病患者血浆UⅡ水平的变化及UⅡ对大鼠VSMC增殖及凋亡的影响。首先采用放免法对心血管疾病患者血浆UⅡ水平测定,在此基础上,采用MTT法、电镜、TUNLE法及流式细胞仪研究UⅡ对大鼠VSMC增殖及凋亡的影响,采用免疫组化方法检测平滑肌细胞Bcl-2/Bax比值。研究结果表明,原发性高血压、不稳定型心绞痛及急性心肌梗死患者血浆UⅡ水平均明显低于健康对照组,且不稳定型心绞痛与急性心肌梗死患者间血浆UⅡ水平存在显著性差异;UⅡ可明显促进大鼠VSMC的增殖,其促增殖作用呈浓度依赖性及时间依赖性;UⅡ在较高浓度范围(10-9～10-6mol/L)内,呈浓度依赖性促进大鼠VSMC凋亡;UⅡ在10-7mol/L浓度时,早期对大鼠VSMC无明显凋亡作用,晚期引起大鼠VSMC凋亡;随UⅡ浓度升高及作用时间延长,Bcl-2蛋白表达无明显变化,但Bax蛋白表达逐渐增强,导致Bcl-2/Bax比值下调,UⅡ可能通过降低Bcl-2/Bax比值诱导大鼠VSMC凋亡。本研究为UⅡ在心血管疾病中可能发挥的作用及机制提供理论基础,但有关UⅡ诱导VSMC增殖与凋亡在心血管疾病的发生发展过程中所发挥的具体作用及发病机制十分复杂,还有待于进一步探讨。
The morbidity and mortality of cardiovascular disease is rapidly increase followed the change of life style and the acceleration of population aging tendency and the younger of cardiovascular disease, so the research about the development mechanism、prevention and therapy of cardiovascular disease is gradually accumulated in recent year. The proliferation and the apoptosis of vascular smooth muscle cells(VSMC) is the co-pathologic base in many cardiovascular disease, such as artherosclerosis、restenosis after interventional therapy and hypertension and so on, so the research of the proliferation and the apoptosis of vascular smooth muscle cells become the central issue on cardiovascular disease prevention and therapy.
The VSMC is the only cell component in intermediate membrane of artery, including shrinkage phenotype and synthesis phenotype. The shrinkage type VSMC is differentiated cell and can not be proliferated. The synthesis type VSMC is dedifferentiation cell and can proliferated. Some research indicated that the VSMC can be changed from differentiation condition to dedifferentiation condition stimulated in vasoconstrictor substances and also can be migrated from intermediate membrane to endomembrane. The artherosclerosis and the restenosis of blood vessel and hypertension are because of the VSMC migration and proliferation, and which induce the thickening of endomembrane and the narrow of blood vessel .The artherosclerosis、the restenosis of blood vessel and the hypertension are happened for the migration and the proliferation of the VSMC in past opinion, but recent research showed that the apoptosis is participated in the process of the cardiovascular disease. In 1985, Thorball observed the cell apoptosis in small artery growth period in mice, the result revealed the apoptosis existence in normal VSMC. In recent year, the VSMC apoptosis was founded in the artherosclerosis、the restenosis of blood vessel and the hypertension. It is consider that the balance of VSMC proliferation and apoptosis will directly influence the quantity of VSMC which will determine the vessel wall thickness and the size of blood vessel.
UⅡis a kind of polypeptide which is made of 11~15 amino acid, widely exists in many species from mollusks to mammals (including humans) .The structure of UⅡin different species are different, but all of them share a common C-terminal cyclic structure, namely, Cys -Phe -Trp– Lys– Tyr-Cys connected through disulfide, this structure from fish to mammals are highly conserved in evolution, it is the active center of UⅡ. UⅡprecursor mRNA was mainly expressed in the cardiovascular and nervous system, and it can also be detected in kidney, spleen, small intestine, thymus, prostate, pituitary and adrenal glands. UⅡreceptor (UT) is an isolated G protein-coupled receptor. In humans, UT expressed throughout the central nervous system, and in peripheral tissues, UT mainly expressed in the cardiovascular system, including ventricles, ventricular, aortic, smooth muscle cells of coronary and aorta, endothelial cells of coronary artery, coronary artery aneurysms and atherosclerotic plaque (especially lipid plaque within the smooth muscle cells and macrophages). UT also expressed in the pancreas and the spinal cord motor neurons, some brain tissue, skeletal muscle and bladder smooth muscle also has the distribution, while the venous endothelial and smooth muscle has no expression. UⅡI and UT had a high affinity, UⅡbinding with UT mediate a series of biological effects, and the effect of post-receptor through CAMP, PLC, phospholipase A2, Ca2+ involved in this process. The current study shows that cardiovascular activity of UⅡinclude:⑴Vasoconstrictor effect: UⅡhas a strong contraction of blood vessels and vasospasm, the artery has stronger role than vein, contraction intensity is greater than norepinephrine, angiotensin and endothelin.UⅡis the strongest vasoconstrictor substances so far.⑵Vasodilator effect: UⅡalso demonstrated some vasodilator effect, which was the only one bi-directional regulation vasoactive peptides.⑶Effects on cell: UⅡis an endogenous mitogen, the same dose of UⅡhad different effects on the different cells, for example, cardiac fibroblasts> airway smooth muscle cells> renal department mesangial cells> vascular smooth muscle cells.⑷On hemodynamic: UⅡcan cause animal or person systemic or local hemodynamic changes, which was related with dose. Small doses reduced peripheral resistance, increased cardiac output, increased coronary perfusion pressure, less affected on blood pressure; large doses increased peripheral resistance, reduced cardiac output, inhibited myocardial contraction, increased blood pressure, lowed coronary perfusion pressure and resulted in myocardial ischemia.Studies have shown that there was a significant difference in plasma levels of UⅡof atherosclerosis, myocardial infarction, interventional treatment, heart failure, cardiomyopathy and hypertension and other cardiovascular diseases compared with the normal population, and UⅡwas the strongest of vasoconstrictor substances so far, which was 8-110 times than ET-1, therefore the study of UⅡon VSMC proliferation and apoptosis has become really important.
In this study, plasma levels of UⅡof hypertension, acute coronary syndrome patients was detected through RIA and compared with normal control group. On the basis of them, to detect the effect of UⅡon rat VSMC proliferation by MTT assay, to detect the effect of UⅡon rat VSMC apoptosis by TEM, TUNLE assay and FCM, and to detect the Bax/Bcl-2 cell ratio by immunohistochemical method.
Clinical study of the experimental results showed that the plasma UⅡlevels in unstable angina and acute myocardial infarction patients were significantly lower than the healthy control group, and the plasma UⅡlevels between unstable angina pectoris and acute myocardial infarction patients have significant difference; the plasma UⅡlevels in patients with essential hypertension were significantly lower than the healthy control group, but plasma UⅡlevels between 2 grade and 3 grade of hypertension have no significant difference; the plasma UⅡlevels in the unstable angina patients with hypertension have no significant difference compared the patients with pure hypertension and those with pure unstable angina; the levels of UⅡhave no relevance with age, gender, BMI, triglyceride and cholesterol.
Foundation study of the experimental results showed that UⅡaccelerate rat VSMC grow significantly , promote the proliferation of rat VSMC significantly, and its proliferation show a dose-dependent and time-dependent manner; UⅡat the higher concentration range promote apoptosis in rat VSMC in a dose-dependent manner; UⅡat 10-7mol/L concentration had no significant role on apoptosis of the rat VSMC in the early stage , caused apoptosis of the rat VSMC in the late stage; meanwhile, UⅡalso has a catalytic role on proliferation cycle of vascular smooth muscle cell, with the concentration of UⅡand the time increasing , cells ratio in G0/G1 phase gradually reduce, that of S phase and G2 / M phase gradually increased; With the increasing of UⅡconcentration, Bcl-2 protein expression have significant change, Bax protein expression gradually increased, and the Bcl-2/Bax ratio reduced; in 10-7mol / L of UⅡincubated culture medium of rat VSMC, Bcl-2, Bax protein expression was no significant difference in the early stage, but the Bax protein expression gradually increased in the late stage, which reduced Bcl-2/Bax ratio, UⅡmay be caused apoptosis rat VSMC by lowering the ratio of Bcl-2/Bax.
These results show that UⅡin cardiovascular disease may be related to induce VSMC proliferation and apoptosis, but development of the specific role and pathogenesis of UⅡ-induced VSMC proliferation and apoptosis in the occurrence of cardiovascular disease must be further explored,The ratio of Bcl-2/ Bax decrease, UⅡpossibly induce the apoptosis of VSMC in this way. The results show that, UⅡas a newer vasoactive substances in recent years, which is related with the occurrence and development of coronary heart disease and hypertension, UⅡmay be involved in the formation of the AS plaque and the AS plaque stability; the mechanism and the strength of UⅡin the pathogenesis of coronary heart disease or hypertension;the change of UⅡlevels in cardiovascular disease may be related to the effect of UⅡon VSMC proliferation and apoptosis;UⅡmaybe induced VSMC apoptosis by lowering the ratio of Bcl-2/Bax.It is very complex that the role of UⅡ-induced VSMC proliferation and apoptosis in the occurrence and development of cardiovascular disease, it remains to be further explored.
The morbidity and mortality of cardiovascular disease is rapidly increase followed the change of life style and the acceleration of population aging tendency and the younger of cardiovascular disease, so the research about the development mechanism、prevention and therapy of cardiovascular disease is gradually accumulated in recent year. The proliferation and the apoptosis of vascular smooth muscle cells(VSMC) is the co-pathologic base in many cardiovascular disease, such as artherosclerosis、restenosis after interventional therapy and hypertension and so on, so the research of the proliferation and the apoptosis of vascular smooth muscle cells become the central issue on cardiovascular disease prevention and therapy.
The VSMC is the only cell component in intermediate membrane of artery, including shrinkage phenotype and synthesis phenotype. The shrinkage type VSMC is differentiated cell and can not be proliferated. The synthesis type VSMC is dedifferentiation cell and can proliferated. Some research indicated that the VSMC can be changed from differentiation condition to dedifferentiation condition stimulated in vasoconstrictor substances and also can be migrated from intermediate membrane to endomembrane. The artherosclerosis and the restenosis of blood vessel and hypertension are because of the VSMC migration and proliferation, and which induce the thickening of endomembrane and the narrow of blood vessel .The artherosclerosis、the restenosis of blood vessel and the hypertension are happened for the migration and the proliferation of the VSMC in past opinion, but recent research showed that the apoptosis is participated in the process of the cardiovascular disease. In 1985, Thorball observed the cell apoptosis in small artery growth period in mice, the result revealed the apoptosis existence in normal VSMC. In recent year, the VSMC apoptosis was founded in the artherosclerosis、the restenosis of blood vessel and the hypertension. It is consider that the balance of VSMC proliferation and apoptosis will directly influence the quantity of VSMC which will determine the vessel wall thickness and the size of blood vessel.
UⅡis a kind of polypeptide which is made of 11~15 amino acid, widely exists in many species from mollusks to mammals (including humans) .The structure of UⅡin different species are different, but all of them share a common C-terminal cyclic structure, namely, Cys -Phe -Trp– Lys– Tyr-Cys connected through disulfide, this structure from fish to mammals are highly conserved in evolution, it is the active center of UⅡ. UⅡprecursor mRNA was mainly expressed in the cardiovascular and nervous system, and it can also be detected in kidney, spleen, small intestine, thymus, prostate, pituitary and adrenal glands. UⅡreceptor (UT) is an isolated G protein-coupled receptor. In humans, UT expressed throughout the central nervous system, and in peripheral tissues, UT mainly expressed in the cardiovascular system, including ventricles, ventricular, aortic, smooth muscle cells of coronary and aorta, endothelial cells of coronary artery, coronary artery aneurysms and atherosclerotic plaque (especially lipid plaque within the smooth muscle cells and macrophages). UT also expressed in the pancreas and the spinal cord motor neurons, some brain tissue, skeletal muscle and bladder smooth muscle also has the distribution, while the venous endothelial and smooth muscle has no expression. UⅡI and UT had a high affinity, UⅡbinding with UT mediate a series of biological effects, and the effect of post-receptor through CAMP, PLC, phospholipase A2, Ca2+ involved in this process. The current study shows that cardiovascular activity of UⅡinclude:⑴Vasoconstrictor effect: UⅡhas a strong contraction of blood vessels and vasospasm, the artery has stronger role than vein, contraction intensity is greater than norepinephrine, angiotensin and endothelin.UⅡis the strongest vasoconstrictor substances so far.⑵Vasodilator effect: UⅡalso demonstrated some vasodilator effect, which was the only one bi-directional regulation vasoactive peptides.⑶Effects on cell: UⅡis an endogenous mitogen, the same dose of UⅡhad different effects on the different cells, for example, cardiac fibroblasts> airway smooth muscle cells> renal department mesangial cells> vascular smooth muscle cells.⑷On hemodynamic: UⅡcan cause animal or person systemic or local hemodynamic changes, which was related with dose. Small doses reduced peripheral resistance, increased cardiac output, increased coronary perfusion pressure, less affected on blood pressure; large doses increased peripheral resistance, reduced cardiac output, inhibited myocardial contraction, increased blood pressure, lowed coronary perfusion pressure and resulted in myocardial ischemia.Studies have shown that there was a significant difference in plasma levels of UⅡof atherosclerosis, myocardial infarction, interventional treatment, heart failure, cardiomyopathy and hypertension and other cardiovascular diseases compared with the normal population, and UⅡwas the strongest of vasoconstrictor substances so far, which was 8-110 times than ET-1, therefore the study of UⅡon VSMC proliferation and apoptosis has become really important.
In this study, plasma levels of UⅡof hypertension, acute coronary syndrome patients was detected through RIA and compared with normal control group. On the basis of them, to detect the effect of UⅡon rat VSMC proliferation by MTT assay, to detect the effect of UⅡon rat VSMC apoptosis by TEM, TUNLE assay and FCM, and to detect the Bax/Bcl-2 cell ratio by immunohistochemical method.
Clinical study of the experimental results showed that the plasma UⅡlevels in unstable angina and acute myocardial infarction patients were significantly lower than the healthy control group, and the plasma UⅡlevels between unstable angina pectoris and acute myocardial infarction patients have significant difference; the plasma UⅡlevels in patients with essential hypertension were significantly lower than the healthy control group, but plasma UⅡlevels between 2 grade and 3 grade of hypertension have no significant difference; the plasma UⅡlevels in the unstable angina patients with hypertension have no significant difference compared the patients with pure hypertension and those with pure unstable angina; the levels of UⅡhave no relevance with age, gender, BMI, triglyceride and cholesterol.
Foundation study of the experimental results showed that UⅡaccelerate rat VSMC grow significantly , promote the proliferation of rat VSMC significantly, and its proliferation show a dose-dependent and time-dependent manner; UⅡat the higher concentration range promote apoptosis in rat VSMC in a dose-dependent manner; UⅡat 10-7mol/L concentration had no significant role on apoptosis of the rat VSMC in the early stage , caused apoptosis of the rat VSMC in the late stage; meanwhile, UⅡalso has a catalytic role on proliferation cycle of vascular smooth muscle cell, with the concentration of UⅡand the time increasing , cells ratio in G0/G1 phase gradually reduce, that of S phase and G2 / M phase gradually increased; With the increasing of UⅡconcentration, Bcl-2 protein expression have significant change, Bax protein expression gradually increased, and the Bcl-2/Bax ratio reduced; in 10-7mol / L of UⅡincubated culture medium of rat VSMC, Bcl-2, Bax protein expression was no significant difference in the early stage, but the Bax protein expression gradually increased in the late stage, which reduced Bcl-2/Bax ratio, UⅡmay be caused apoptosis rat VSMC by lowering the ratio of Bcl-2/Bax.
These results show that UⅡin cardiovascular disease may be related to induce VSMC proliferation and apoptosis, but development of the specific role and pathogenesis of UⅡ-induced VSMC proliferation and apoptosis in the occurrence of cardiovascular disease must be further explored,The ratio of Bcl-2/ Bax decrease, UⅡpossibly induce the apoptosis of VSMC in this way. The results show that, UⅡas a newer vasoactive substances in recent years, which is related with the occurrence and development of coronary heart disease and hypertension, UⅡmay be involved in the formation of the AS plaque and the AS plaque stability; the mechanism and the strength of UⅡin the pathogenesis of coronary heart disease or hypertension;the change of UⅡlevels in cardiovascular disease may be related to the effect of UⅡon VSMC proliferation and apoptosis;UⅡmaybe induced VSMC apoptosis by lowering the ratio of Bcl-2/Bax.It is very complex that the role of UⅡ-induced VSMC proliferation and apoptosis in the occurrence and development of cardiovascular disease, it remains to be further explored.
引文
[1] Pearson D,Shively JE,Clark BR,et al.UrotensinⅡ:a somatostatin-like peptide in the caudal neurosecretory system of fishes[J].Proc Natl Acad Sci USA,1980, 77(8):5021-4.
[2] Coulouarn Y,Lihrmann I, Jegou S,et al. Cloning of the cDNA encoding the urotensinⅡprecursor in frog and human reveals intense expression of the urotensinⅡgene in motoneurons of the spinal cord[J]. Proc Natl Acad Sci USA, 1998,95(26):15 803-8.
[3] Ames RS, Sarau H M,Chambers J D,et al. Human urotensinⅡis a potent vasoconstrictor and agonist for the orphan receptor GPR14[J]. Nature,1999,401(6750):282-6.
[4] Russell FD,Kearns P,Toth I,et al.Urotensin-Ⅱ-converting enzyme activity of furin and trypsin in human cells in vitro[J].J Pharmacol Exp Ther,2004,310(1):209-14.
[5] Maguire JJ,Kuc RE, Davenport AP. Orphan-receptor ligand human urotensinⅡ: receptor localization in human tissues and comparison of vasoconstrictor responses with endothlin-1. Br J Pharmacol, 2000,131(3):441.
[6] Douglas SA,Sulpizio AC,Piercy V,Sarau HM, Ames RS,et al. Differential vasoconstrictor activity of human urotensinⅡin vascular tissue isolated from the rat , mouse, dog,pig,mamorset and cynomolgus monkey. Br J Pharmacol,2000,131(7):1262-74.
[7] Liu Q,Pong SS,Zeng Z,et al.Identification of urotensinⅡas the endogenous ligand for the orphan G-protein-coupled receptor GPR14[J].Biochem Biophys Res Commun,1999,266:174-8.
[8]Mori M,Sugo t T,Abe M,et al.UrotensinⅡis the endougenous ligand of a G-protein coupled orphan recaptor SENR(GPR14).Biochem Biophys ResCommun,1999,265:123-9
[9] Opgaard OS,NothackerⅡ, Ehlert FJ, Krause DN. Human urotensinⅡmediates vasoconstrection via an increase in inosito phosphates. Eur J Phanmacol,2000,406(2):265-71
[10] Gupta OP,Hanke W. Regulation of interremalsecretion in the axolotl, Ambystoma mexicanum. Exp Clin Endocrinol,1994,102(4):299-306.
[11] Le-Mevel JC,Olson KR,Conklin D,et al. Cardovascular actionsaof trout urotensinⅡin the conscious trout,oncorhynchus mykiss.Am J Physiol,1996,271:R1335-43.
[12] Yano K,Hicks JW,Vaudry H,et al.Cardiovascular action of frog urotensinⅡin the frog,Rana catesbeiana[J].Gen Comp Endocrinol,1995,97(1):103-10.
[13] Maclean MR,Alexander,Sterrat ,Gallagher M,Douglas SA. Ohlstein EH. Et al.Contractile responses to human urotensinⅡin rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat. Br J Pharmacol,2001,130(2):201-4.
[14] Bottill FE,Douglas SA,Hiley CR,White R. Human urotinsinⅡis an endothelium- dependent vasodilator in rat small arteries. Eur J Pharmacol,2000,130(8):1865-70.
[15] Maguire JJ,Kuc RE, Davenport AP. Orphan-receptor ligand human urotensinⅡ: receptor localization in human tissues and comparison of vasoconstrictor responses with endothlin-1. Br J Pharmacol,2000,131(3):441.
[16] Hillier C , Berry C, Petrie MC, et al. Effects of urotensinⅡin human arteries and veins of varying caliber [J]. Circulation,2001,103(10):1378-81.
[17] Itoh H,Itoh Y,Rivier J,et al.Contraction of major artery segments of rat by fish neuropeptide urotensinⅡ[J].Am J Physiol,1987,252:R361-6.
[18] Gibson A. Complex effects of Gillichthys urotensinⅡon rat aorticstrips.Br J Pharmacol,1987,91(1):205-12.
[19] Watanbe T,Pakala R Karagiri T,et al. Synergistic effect of urotensinⅡwith midly oxidized LDLon DNA synthesis in vascular smooth muscle cells. Cirdiovasc Res,2002,104(1):16.
[20] Rossowski WJ, Cheng BL, Taylor JE, et al. Human urotensinⅡ-induced aorta ring contractions are mediated by protein kinase C, tyrosine kinases and Rho-kinase: inhibition by somatostatin receptor antagonists. Eur J Pharmacol,2002,438(3):159-70.
[21] Sauzeau V, Le Mellionnec E, Bertoglio J, Scalbert E, Pacaud P, Loirand G. Human urotensinⅡ-induced contraction and arterial smooth muscle cell proliferation are mediated by RhoA and Rho-kinase.Circ Res,2001,88(11):1102-4.
[22] Stirrat Agallsgher M, Douglas S A, et al. Potent vasodilator responses to human urotensinⅡin human pulmonary and abdominal resistance arteries[J]. AmJ Physiol,2001,280(2):H925-8.
[23] Camarda V,Rizzi A,Calo G,Gendron G,Perron SI, Kostenis E,et al. Effects of human urotensinⅡin isolated vessels of various species: companson with other vasoactive agents. Naunyn Schmiedebergs Arch Pharmacol,2002,365(2):141-9.
[24]姜志胜,张勇刚,齐永芬,等.尾加压素Ⅱ对大鼠主动脉NO生成的影响[J].北京医科大学学报,2001,33(2):147-9.
[25] Lin Y,T suchihashi T,Matsumura K,et al. Central cardiovascular action of urotensinⅡin conscious rat[J]. J Hypertens, 2003,21(1):159-65.
[26]张勇刚,齐永芬,夏春芳,等.尾加压素Ⅱ对血管平滑肌细胞增殖的影响[J].中国药理学通报,2001,17(2):155-7.
[27]杨竞霄,赵连发,郑强荪,等.尾加压素Ⅱ对乳鼠心肌成纤维细胞增殖的影响及细胞内信号转导机制[J].第四军医大学学报,2004,25(6):519-22
[28] Zou Y, Nagai R, Yamazake T. UrotensinⅡinduces hypertrophic responses in cultured cardiomyocytes from neonatal rats. FEBS Lett, 2001, 508(1):57-60.
[29] Doggrell SA.The role of 5-HT on the cardiovascular and renal systems and theclini- cal potential of 5-HT modulation[J ]. Expert Opin Investig Drugs, 2003 , 12(5):805-23.
[30]陈军红,赵连友,郑强荪,等.尾加压素Ⅱ对新生大鼠心肌细胞肥大的影响[J].第四军医大学学报,2004,25(7):641-3.
[31]王琼,王汉,喻维,等.尾加压素Ⅱ诱导人脐血管平滑肌细胞肥大及其机制探讨[J].山东医药,2006,46(36),23-4.
[32] Shi L, Ding W, Li D, et al.Proliferation and anti-apoptotic effects of human urotensinⅡon human endothelial cells[J]. Atherosclerosis, 2006 , 188(2):260-4.
[33]顾晓龙,严全能,张园,等.尾加压素Ⅱ对人脐静脉内皮细胞凋亡的影响[J].实用医学杂志,2006,22(11):1228-30.
[34] Bohm F, Pernow J. UrotensinⅡevokes potent vasoconstriction in human in vivo[J]. Br J Pharmacol,2002,135(1):25-7.
[35] Wildinson B,Affolter T,de Haas L,et al.High plasma concentrations of human urotensinⅡdo not alter local or systemic hemodynamics in man[J]. Cardiovase Res, 2002,53(2):341.
[36] Lambert DG. UrotensinⅡ: from osmoregulation in fish to cardiovas- cular regulation in man. Br J Anaesthesia, 2007,98:557-9.
[37]涂晓文,刘映峰,李志墚,等.尾加压素Ⅱ在冠状动脉中的表达与冠状动脉粥样硬化[J].第一军医大学学报,2003,23(6),572-4.
[38] Tzanidis A, Hannan RD, Th omas WG, et al. Direct actions of urotensinⅡon the heart: implications for cardiac fibrosis and hypertrophy [J] . Circ Res, 2003,93:246-53.
[39]方石虎,吴宏超,唐朝枢,等.冠心病患者血浆尾加压素Ⅱ的临床研究[J].第一军医大学学报,2004,24(5):563-5.
[40]曹军,张勇刚,齐永芬,等.血浆尾加压素Ⅱ含量在几种疾病中的变化[J].放射免疫学杂志,2001,14(4):195-7.
[41]史力斌,丁文惠,杨俊娟,等.缺血性心脏病患者血浆尾加压素Ⅱ水平的变化及意义[J].中华内科杂志,2001,41(7):634-5.
[42] Joyal D,HuynhT,Aiyar N,et al. UrotensinⅡlevels in acute coronary syndromes [J]. Kidney Int, 2006 ,108(1):31-5..
[43]杨俊娟,林文华,张勇刚,等.冠状动脉粥样硬化及其介入治疗术后血浆尾加压素Ⅱ水平变化的研究[J].中华老年心脑血管病杂志,2001 ,3(6):373-5.
[44]周启林,田国平.尾加压素Ⅱ与高血压的相关性研究[J].岭南心血管病杂志,2005,11(6):430-1.
[45]富路,朱立群,戴颖楠,等.高血压患者血浆尾加压素Ⅱ的变化[J].中华高血压杂志,2007,15(2):159-60.
[46]张捃辉,张靖傅.尾加压素Ⅱ与高血压病的相关性[J].中国全科医学,2003,6:640-1.
[47] Douglas SA, Tayara L, Ohlstein EH, et al.Congestive heart failure and expression of myocardial urotensinⅡ[ J ] .Lancet,2002,359:1990-7.
[48] Dschietzig T, Bartsch C, Pregla R, et al. Plasma levels and cardiovascular gene expr- ession of urotensin-Ⅱin human heart failure [ J ] .Regul Pept, 2002,110(1):33-8.
[49] Kruger S, Graf J , KunzDEur, et al. UrotensinⅡin patients with chronic heart failure [J]. Eur J Heart Fail,2005,7(4):475-8.
[50] Richards AM, NichollsMG, Lainchbury JG, et al. Plasma urotensinⅡin heart failure[ J ]. Lancet,2002,360:545-6.
[51] Ng LL , Loke I , O’Brien RJ,et al. Plasma urotensin in human systolic heartfailure [J].Circulation,2002, 106:2877-80.
[52]钟萍,李志墚,吴宏超,等.充血性心力衰竭患者血浆尾加压素Ⅱ变化的临床研究[J].第一军医大学学报,2003,23(2):121-3.
[53] Lapp H, Boerrigter G, Costello-Boerrigter LC, et al. Elevated plasma human urotensin-Ⅱ-like mmunoreactivity in ischemic cardiomyopathy[J]. Int J Cardiol , 2004, 94:93– 97.
[54] Behm DJ, Herold CL, Ohlstein EH, et al. Pharmacological characterization of SB-710411 (Cpa- c[D- Cys- Pal- D- Trp- Lys- Val- Cys]- Cpa-amide),a novel peptidic urotensin-Ⅱreceptor antagonist. Br J Pharmacol, 2002 , 137(4):449-58.
[55] Patacchini R, Santicioli P, Giuliani S,et al.Urantide: an ultrapotent urotensinⅡantagonist peptide in the rat aorta,Br J Pharmacol,2003 ,140(7):1155-8.
[56] Chatenet D,Dubessy C,Leprince J,et al. Structure-activity relationships and structural conformation of a novel urotensinⅡ-related peptide[J]. Peptides,2004,25(10):1819-30
[57] MORL M,SUGO T,ABE M,et al.UrotensinⅡis the enkogenous ligand of a G-protein-coupled receptor,SENR (GPR14)[J]. Biochem Biophys Res Commun, 1999, 265(1):123-9.
[58] Thorball N, Moe H, Winther-Nielsen H.Progressive involution and physiological death of smooth muscle cells of rat incisal arterioles.Blood Vessels. 1985;22(4):157-69.
[59]彭刚艺,凌文华.氧化型低密度脂蛋白诱导大鼠血管平滑肌细胞凋亡[J].中国动脉硬化杂志,1999, 7(2):140-4.
[60] Barbro B , Soren B. Contrary effects of lightly and strongly oxidized LDL with potent promotion of growth versus apoptosis on arterial smooth muscle cells , macrophages , and fibroblasts. Arterioscler Thromb Vasc Biol ,1996 , 16 : 416-24
[61] Subrote Chafterjee. Role of oxidized human plasma low density lipoprteins in atherosclerosis : Effects on smooth muscle cell prolification. Mol Cell Biochem , 1992 , 111 : 143-7.
[62] Eisuke Nishio. Oxysterols induced apoptosis in cultured smooth muscle cells through cpp 32 proteinase activation and bcl22 protein down regulation. Biochem Biophy Res Comm , 1996 , 226 : 928-34.
[63] Bachem MG, Wendelin D, Schneiderhan W, Haug C, Zorn U, Gross HJ, Schmid- Kotsas A, Grünert A.Depending on their concentration oxidized low density lipoproteins stimulate extracellular matrix synthesis or induce apoptosis in human coronary artery smooth muscle cells.Clin Chem Lab Med,1999 ,37(3):319-26.
[64]郭峰,严奉祥.血管平滑肌细胞凋亡机制的研究进展[J].心血管病学进展,2006,27(2):218-20.
[65] Boyle JJ, Weissberg PL, Bennett MR. Human macrophage-induced vascular smooth muscle cell apoptosis requires NO enhancement of Fas /Fas-L interactions[J]. Arterioscler Thromb Vasc Biol,2002,22(10):1624- 30.
[66]郭媛,朱清,岳欣,等.血管紧张素Ⅱ对血管平滑肌细胞增殖与凋亡的影响[J].山东大学学报:医学版,2004,42(5):552-5.
[67]梁绪国,戚加永,陈红英.药物对血管紧张素Ⅱ致平滑肌细胞凋亡的影响[J].药物流行病学杂志,2005,14(3):129-31.
[68] Bochaton-Piallat ML, Gabbiani F, Redard M, Desmoulière A, Gabbiani G. Apoptosis participates in cellularity regulation during rat aortic intimal thickening.Am J Pathol,1995,146(5),1059-64.
[69] Mayr M, Li C, Zou Y, Huemer U, Hu Y, Xu Q.Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases.FASEB J,2000 ,14(2):261-70.
[70] Leskinen MJ, Heikkil? HM, Speer MY, Hakala JK, Laine M, Kovanen PT, Lindstedt KA.Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF- kappaB- mediated survival signaling.Exp Cell Res,2006,312(8):1289-98.
[71]王祥贵,冯义柏,朱利民,等.同型半胱氨酸对人血管平滑肌细胞凋亡及Bax、Bcl-2表达的影响[J].中国全科医学,2005,8(6):446-9.
[72] Streb JW, Miano JM.Retinoids: pleiotropic agents of therapy for vascular diseases? Curr Drug Targets Cardiovasc Haematol Disord,2003,3(1):31-57.
[73]王溪涛,刘波,张炎,等.低切应力对动脉粥样硬化血管平滑肌细胞Bcl-2和Bax蛋白表达的影响[J].解剖学报,2005,36(5):567-9.
[74] Bj?rkerud S, Bj?rkerud B, Joelsson M.Structural organization of reconstituted human arterial smooth muscle tissue.Arterioscler Thromb.1994 Apr;14(4):644-51.
[75] Han DK, Haudenschild CC, HongMK, et al. Evidence for apoptosis in human atherogenesis and in a rat vascular injurymodel[ J ]. Am J Pathol, 2003, 155 (2) : 267 - 77.
[76] David K, Han M, Handenschild CC , et al . Evidence for apoptosis in human atherosclerosis and in a rat vascular injury model . Am J Pathol ,1995 , 147 : 267 - 77
[77] Bennett M R ,Evan G I ,Schwartz S M. Apoptosis of human vascular smooth muscle cells deriverd from normal vessels and coronary atherosclerotic plaques [J ] . J Clin Invest , 1995 , 96(5) :2266– 74.
[78] Diez J , Panizo A. Is the regulation of apoptosis altered in smooth muscle cells of adult SHR[J ] Hypertens ,1997 ,29 :776.
[79]黄文新,阳跃忠,夏中华,等.色满卡林对自发性高血压大鼠血管平滑肌细胞凋亡的影响[J].中国新药与临床杂志,2006,25(6):401-4.
[80]周园,周家国,丘钦英,等.CIC-3氯通道对H2O2诱导的大鼠主动脉平滑肌细胞凋亡的影响[J].中国药理学通报,2006,22(10):1175-9.
[81] Hamet P , Richard L , Dam TV, et al .Apoptosis in target organs of hypertension[J].Hypertension ,1995,26:6421.
[82]余良生,化长林,黄碧兰,等.L-精氨酸对高血压大鼠主动脉平滑肌细胞凋亡的影响[J].咸宁学院学报:医学版2006,19(5):1175-9.
[83]景丽,张建中,秦璟,等.凋亡相关基因Bcl-6和Bax在高血压大鼠血管平滑肌细胞中的表达[J].宁夏医学院学报,2004,26(2):79-83.
[84] Inser JM,Kearney M,Bortman S ,et al . Apoptosis in human atherosclerosis and restenosis[J ] . Circulation ,1995 ,91(11) :2703.
[85] BauriedelG,HeidemannP,HeimerlJ,et al. Apoptosis inrest enosisver susstable- angina atherosclerosis. Arterioscler Thromb Vasc Biol,1998, 18:1132 -9.
[86] Kockx MM, DeMeyer GR, Muhring J, et al. Apotisis and related proteins in different stages of human atherosclerotic plaque [ J ].Circulation, 1998,97 (23) :237 - 9.
[87]李大勇,车艳,杨镛,等.腹主动脉瘤动脉壁血管平滑肌细胞增殖及凋亡的研究[J].中华普通外科杂志,2004,19(3):169-71.
[88] Fontaine V ,Jacob MP ,Houard X, et al . Involvement of the mural thrombus as a site of protease release and activation in human aortic aneurysms[J ] . Am J Pathol,2002 ,161 (5):1701-10.
[89]郭付有,宋来君,冯祖荫,等.流体切应力对大鼠血管平滑肌细胞凋亡的影响[J].中原医刊,2007,34(6):9-11.
[90] Saxena A, McMeekin JD, Thomson DJ. Expression of Bcl-x, Bcl-2, Bax, and Bak in endarterectomy and atherectomy specimens. J Pathol. 2002, 196(3):335-42
[91] Degterev A, Lugovskoy A, Cardone M, et al.Identification of small-molecule inhibitors of internation between the BH3 domain and Bcl-xL[J]. Nat Cell Biol, 2001,3(2):173- 82.
[92] Chiou FL,Chia LC,Chang WT,et al. Bcl-2 rescues ceramide and etoposide-induced mitochondrial apoptosis is through blockage of caspase-2 activation[J]. J Biol Chem,2005,280(25):23758- 65.
[93] Forte A, Galderisi U, De Feo M, et al. c-Myc antisense oligonucleotides preserve smooth muscle differentiation and reduce negative remodelling following rat carotid arteriotomy. J Vasc Res,2005,42(3):214-25.
[94] Jiang C,Yang YF,Cheng SH. Fas ligand gene therapyfor vascular intimal hyperplasia[J]. Curr Gene Ther,2004,4(1):33- 9.
[95] Matsumura ME,LI P,Berthoux L, et al. Vascular injury induces posttranscriptional regulation of the Id3 gene:cloning of a novel Id3 isoform expressed during vascular lesion formation in rat and human atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2001,21(5):752- 58.
[96]司艳红,王家富.动脉粥样硬化与平滑肌细胞凋亡的调控[J].中国临床康复,2005,9(47): 118-20.
[97] Prter,A.G.,Janicke,R.U. Emerging roles of caspase-3 in apoptosis. Cell Death Diff,1999,6:99-104.
[98] Zou,H. Li,Y. Liu,X.& Wang,X. An APAF-1 cytochrome c complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem,1999, 274:11549-56.
[99] Rdzanek A,Filipiak KJ,Karpinaki G,et al. Exercise urotensinⅡdynamics in myocardial infarction survivors with and without hypertension[J]. Peptides,2005,26(12): 2464-72.
[100] Stephen AD, Ohstein EH,Halawa N, et al. Congestive heart failure and expression of myocardial urotensinⅡinfusion in humans[J].Br J Clin Pharmacol, 2002,54(6):617-21.
[101]温进坤,韩梅.血管平滑肌细胞[M].北京:科学出版社,2005.
[102]刘红梅,黄体钢.血管平滑肌细胞的培养及其在血管疾病研究中的作用[J].实用心脑肺血管病杂志,2005,13(6):363-9
[103]彭黎明,王曾礼.细胞凋亡的基础与临床[M].北京:人民卫生出版社,2000.
[104]司徒镇强,吴军正.细胞培养[M].第二版.北京:世界图书出版社,2007.
[105]戴恩来,薛国忠,武俊斌,等.大鼠血管平滑肌细胞的贴块法培养[J].中医儿科杂志,2007,3(2):47-9
[106]陈焰炫、刘健康.动脉平滑肌细胞原代培养贴块法的改良[J].生物学杂志,2002,19(4):27-8.
[107]王伯沄,李玉松,黄高昇,等.病理学技术[M].北京:人民卫生出版社,2001.
[108] Rose R.Atherosolereosis-an inflammatory disease[J].N Eng J Med.1999,340(2):115- 26.
[109]沃兴德,丁志山.细胞凋亡与动脉粥样硬化[J].浙江中医学院学报,2001,25:76-7
[2] Coulouarn Y,Lihrmann I, Jegou S,et al. Cloning of the cDNA encoding the urotensinⅡprecursor in frog and human reveals intense expression of the urotensinⅡgene in motoneurons of the spinal cord[J]. Proc Natl Acad Sci USA, 1998,95(26):15 803-8.
[3] Ames RS, Sarau H M,Chambers J D,et al. Human urotensinⅡis a potent vasoconstrictor and agonist for the orphan receptor GPR14[J]. Nature,1999,401(6750):282-6.
[4] Russell FD,Kearns P,Toth I,et al.Urotensin-Ⅱ-converting enzyme activity of furin and trypsin in human cells in vitro[J].J Pharmacol Exp Ther,2004,310(1):209-14.
[5] Maguire JJ,Kuc RE, Davenport AP. Orphan-receptor ligand human urotensinⅡ: receptor localization in human tissues and comparison of vasoconstrictor responses with endothlin-1. Br J Pharmacol, 2000,131(3):441.
[6] Douglas SA,Sulpizio AC,Piercy V,Sarau HM, Ames RS,et al. Differential vasoconstrictor activity of human urotensinⅡin vascular tissue isolated from the rat , mouse, dog,pig,mamorset and cynomolgus monkey. Br J Pharmacol,2000,131(7):1262-74.
[7] Liu Q,Pong SS,Zeng Z,et al.Identification of urotensinⅡas the endogenous ligand for the orphan G-protein-coupled receptor GPR14[J].Biochem Biophys Res Commun,1999,266:174-8.
[8]Mori M,Sugo t T,Abe M,et al.UrotensinⅡis the endougenous ligand of a G-protein coupled orphan recaptor SENR(GPR14).Biochem Biophys ResCommun,1999,265:123-9
[9] Opgaard OS,NothackerⅡ, Ehlert FJ, Krause DN. Human urotensinⅡmediates vasoconstrection via an increase in inosito phosphates. Eur J Phanmacol,2000,406(2):265-71
[10] Gupta OP,Hanke W. Regulation of interremalsecretion in the axolotl, Ambystoma mexicanum. Exp Clin Endocrinol,1994,102(4):299-306.
[11] Le-Mevel JC,Olson KR,Conklin D,et al. Cardovascular actionsaof trout urotensinⅡin the conscious trout,oncorhynchus mykiss.Am J Physiol,1996,271:R1335-43.
[12] Yano K,Hicks JW,Vaudry H,et al.Cardiovascular action of frog urotensinⅡin the frog,Rana catesbeiana[J].Gen Comp Endocrinol,1995,97(1):103-10.
[13] Maclean MR,Alexander,Sterrat ,Gallagher M,Douglas SA. Ohlstein EH. Et al.Contractile responses to human urotensinⅡin rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat. Br J Pharmacol,2001,130(2):201-4.
[14] Bottill FE,Douglas SA,Hiley CR,White R. Human urotinsinⅡis an endothelium- dependent vasodilator in rat small arteries. Eur J Pharmacol,2000,130(8):1865-70.
[15] Maguire JJ,Kuc RE, Davenport AP. Orphan-receptor ligand human urotensinⅡ: receptor localization in human tissues and comparison of vasoconstrictor responses with endothlin-1. Br J Pharmacol,2000,131(3):441.
[16] Hillier C , Berry C, Petrie MC, et al. Effects of urotensinⅡin human arteries and veins of varying caliber [J]. Circulation,2001,103(10):1378-81.
[17] Itoh H,Itoh Y,Rivier J,et al.Contraction of major artery segments of rat by fish neuropeptide urotensinⅡ[J].Am J Physiol,1987,252:R361-6.
[18] Gibson A. Complex effects of Gillichthys urotensinⅡon rat aorticstrips.Br J Pharmacol,1987,91(1):205-12.
[19] Watanbe T,Pakala R Karagiri T,et al. Synergistic effect of urotensinⅡwith midly oxidized LDLon DNA synthesis in vascular smooth muscle cells. Cirdiovasc Res,2002,104(1):16.
[20] Rossowski WJ, Cheng BL, Taylor JE, et al. Human urotensinⅡ-induced aorta ring contractions are mediated by protein kinase C, tyrosine kinases and Rho-kinase: inhibition by somatostatin receptor antagonists. Eur J Pharmacol,2002,438(3):159-70.
[21] Sauzeau V, Le Mellionnec E, Bertoglio J, Scalbert E, Pacaud P, Loirand G. Human urotensinⅡ-induced contraction and arterial smooth muscle cell proliferation are mediated by RhoA and Rho-kinase.Circ Res,2001,88(11):1102-4.
[22] Stirrat Agallsgher M, Douglas S A, et al. Potent vasodilator responses to human urotensinⅡin human pulmonary and abdominal resistance arteries[J]. AmJ Physiol,2001,280(2):H925-8.
[23] Camarda V,Rizzi A,Calo G,Gendron G,Perron SI, Kostenis E,et al. Effects of human urotensinⅡin isolated vessels of various species: companson with other vasoactive agents. Naunyn Schmiedebergs Arch Pharmacol,2002,365(2):141-9.
[24]姜志胜,张勇刚,齐永芬,等.尾加压素Ⅱ对大鼠主动脉NO生成的影响[J].北京医科大学学报,2001,33(2):147-9.
[25] Lin Y,T suchihashi T,Matsumura K,et al. Central cardiovascular action of urotensinⅡin conscious rat[J]. J Hypertens, 2003,21(1):159-65.
[26]张勇刚,齐永芬,夏春芳,等.尾加压素Ⅱ对血管平滑肌细胞增殖的影响[J].中国药理学通报,2001,17(2):155-7.
[27]杨竞霄,赵连发,郑强荪,等.尾加压素Ⅱ对乳鼠心肌成纤维细胞增殖的影响及细胞内信号转导机制[J].第四军医大学学报,2004,25(6):519-22
[28] Zou Y, Nagai R, Yamazake T. UrotensinⅡinduces hypertrophic responses in cultured cardiomyocytes from neonatal rats. FEBS Lett, 2001, 508(1):57-60.
[29] Doggrell SA.The role of 5-HT on the cardiovascular and renal systems and theclini- cal potential of 5-HT modulation[J ]. Expert Opin Investig Drugs, 2003 , 12(5):805-23.
[30]陈军红,赵连友,郑强荪,等.尾加压素Ⅱ对新生大鼠心肌细胞肥大的影响[J].第四军医大学学报,2004,25(7):641-3.
[31]王琼,王汉,喻维,等.尾加压素Ⅱ诱导人脐血管平滑肌细胞肥大及其机制探讨[J].山东医药,2006,46(36),23-4.
[32] Shi L, Ding W, Li D, et al.Proliferation and anti-apoptotic effects of human urotensinⅡon human endothelial cells[J]. Atherosclerosis, 2006 , 188(2):260-4.
[33]顾晓龙,严全能,张园,等.尾加压素Ⅱ对人脐静脉内皮细胞凋亡的影响[J].实用医学杂志,2006,22(11):1228-30.
[34] Bohm F, Pernow J. UrotensinⅡevokes potent vasoconstriction in human in vivo[J]. Br J Pharmacol,2002,135(1):25-7.
[35] Wildinson B,Affolter T,de Haas L,et al.High plasma concentrations of human urotensinⅡdo not alter local or systemic hemodynamics in man[J]. Cardiovase Res, 2002,53(2):341.
[36] Lambert DG. UrotensinⅡ: from osmoregulation in fish to cardiovas- cular regulation in man. Br J Anaesthesia, 2007,98:557-9.
[37]涂晓文,刘映峰,李志墚,等.尾加压素Ⅱ在冠状动脉中的表达与冠状动脉粥样硬化[J].第一军医大学学报,2003,23(6),572-4.
[38] Tzanidis A, Hannan RD, Th omas WG, et al. Direct actions of urotensinⅡon the heart: implications for cardiac fibrosis and hypertrophy [J] . Circ Res, 2003,93:246-53.
[39]方石虎,吴宏超,唐朝枢,等.冠心病患者血浆尾加压素Ⅱ的临床研究[J].第一军医大学学报,2004,24(5):563-5.
[40]曹军,张勇刚,齐永芬,等.血浆尾加压素Ⅱ含量在几种疾病中的变化[J].放射免疫学杂志,2001,14(4):195-7.
[41]史力斌,丁文惠,杨俊娟,等.缺血性心脏病患者血浆尾加压素Ⅱ水平的变化及意义[J].中华内科杂志,2001,41(7):634-5.
[42] Joyal D,HuynhT,Aiyar N,et al. UrotensinⅡlevels in acute coronary syndromes [J]. Kidney Int, 2006 ,108(1):31-5..
[43]杨俊娟,林文华,张勇刚,等.冠状动脉粥样硬化及其介入治疗术后血浆尾加压素Ⅱ水平变化的研究[J].中华老年心脑血管病杂志,2001 ,3(6):373-5.
[44]周启林,田国平.尾加压素Ⅱ与高血压的相关性研究[J].岭南心血管病杂志,2005,11(6):430-1.
[45]富路,朱立群,戴颖楠,等.高血压患者血浆尾加压素Ⅱ的变化[J].中华高血压杂志,2007,15(2):159-60.
[46]张捃辉,张靖傅.尾加压素Ⅱ与高血压病的相关性[J].中国全科医学,2003,6:640-1.
[47] Douglas SA, Tayara L, Ohlstein EH, et al.Congestive heart failure and expression of myocardial urotensinⅡ[ J ] .Lancet,2002,359:1990-7.
[48] Dschietzig T, Bartsch C, Pregla R, et al. Plasma levels and cardiovascular gene expr- ession of urotensin-Ⅱin human heart failure [ J ] .Regul Pept, 2002,110(1):33-8.
[49] Kruger S, Graf J , KunzDEur, et al. UrotensinⅡin patients with chronic heart failure [J]. Eur J Heart Fail,2005,7(4):475-8.
[50] Richards AM, NichollsMG, Lainchbury JG, et al. Plasma urotensinⅡin heart failure[ J ]. Lancet,2002,360:545-6.
[51] Ng LL , Loke I , O’Brien RJ,et al. Plasma urotensin in human systolic heartfailure [J].Circulation,2002, 106:2877-80.
[52]钟萍,李志墚,吴宏超,等.充血性心力衰竭患者血浆尾加压素Ⅱ变化的临床研究[J].第一军医大学学报,2003,23(2):121-3.
[53] Lapp H, Boerrigter G, Costello-Boerrigter LC, et al. Elevated plasma human urotensin-Ⅱ-like mmunoreactivity in ischemic cardiomyopathy[J]. Int J Cardiol , 2004, 94:93– 97.
[54] Behm DJ, Herold CL, Ohlstein EH, et al. Pharmacological characterization of SB-710411 (Cpa- c[D- Cys- Pal- D- Trp- Lys- Val- Cys]- Cpa-amide),a novel peptidic urotensin-Ⅱreceptor antagonist. Br J Pharmacol, 2002 , 137(4):449-58.
[55] Patacchini R, Santicioli P, Giuliani S,et al.Urantide: an ultrapotent urotensinⅡantagonist peptide in the rat aorta,Br J Pharmacol,2003 ,140(7):1155-8.
[56] Chatenet D,Dubessy C,Leprince J,et al. Structure-activity relationships and structural conformation of a novel urotensinⅡ-related peptide[J]. Peptides,2004,25(10):1819-30
[57] MORL M,SUGO T,ABE M,et al.UrotensinⅡis the enkogenous ligand of a G-protein-coupled receptor,SENR (GPR14)[J]. Biochem Biophys Res Commun, 1999, 265(1):123-9.
[58] Thorball N, Moe H, Winther-Nielsen H.Progressive involution and physiological death of smooth muscle cells of rat incisal arterioles.Blood Vessels. 1985;22(4):157-69.
[59]彭刚艺,凌文华.氧化型低密度脂蛋白诱导大鼠血管平滑肌细胞凋亡[J].中国动脉硬化杂志,1999, 7(2):140-4.
[60] Barbro B , Soren B. Contrary effects of lightly and strongly oxidized LDL with potent promotion of growth versus apoptosis on arterial smooth muscle cells , macrophages , and fibroblasts. Arterioscler Thromb Vasc Biol ,1996 , 16 : 416-24
[61] Subrote Chafterjee. Role of oxidized human plasma low density lipoprteins in atherosclerosis : Effects on smooth muscle cell prolification. Mol Cell Biochem , 1992 , 111 : 143-7.
[62] Eisuke Nishio. Oxysterols induced apoptosis in cultured smooth muscle cells through cpp 32 proteinase activation and bcl22 protein down regulation. Biochem Biophy Res Comm , 1996 , 226 : 928-34.
[63] Bachem MG, Wendelin D, Schneiderhan W, Haug C, Zorn U, Gross HJ, Schmid- Kotsas A, Grünert A.Depending on their concentration oxidized low density lipoproteins stimulate extracellular matrix synthesis or induce apoptosis in human coronary artery smooth muscle cells.Clin Chem Lab Med,1999 ,37(3):319-26.
[64]郭峰,严奉祥.血管平滑肌细胞凋亡机制的研究进展[J].心血管病学进展,2006,27(2):218-20.
[65] Boyle JJ, Weissberg PL, Bennett MR. Human macrophage-induced vascular smooth muscle cell apoptosis requires NO enhancement of Fas /Fas-L interactions[J]. Arterioscler Thromb Vasc Biol,2002,22(10):1624- 30.
[66]郭媛,朱清,岳欣,等.血管紧张素Ⅱ对血管平滑肌细胞增殖与凋亡的影响[J].山东大学学报:医学版,2004,42(5):552-5.
[67]梁绪国,戚加永,陈红英.药物对血管紧张素Ⅱ致平滑肌细胞凋亡的影响[J].药物流行病学杂志,2005,14(3):129-31.
[68] Bochaton-Piallat ML, Gabbiani F, Redard M, Desmoulière A, Gabbiani G. Apoptosis participates in cellularity regulation during rat aortic intimal thickening.Am J Pathol,1995,146(5),1059-64.
[69] Mayr M, Li C, Zou Y, Huemer U, Hu Y, Xu Q.Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases.FASEB J,2000 ,14(2):261-70.
[70] Leskinen MJ, Heikkil? HM, Speer MY, Hakala JK, Laine M, Kovanen PT, Lindstedt KA.Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF- kappaB- mediated survival signaling.Exp Cell Res,2006,312(8):1289-98.
[71]王祥贵,冯义柏,朱利民,等.同型半胱氨酸对人血管平滑肌细胞凋亡及Bax、Bcl-2表达的影响[J].中国全科医学,2005,8(6):446-9.
[72] Streb JW, Miano JM.Retinoids: pleiotropic agents of therapy for vascular diseases? Curr Drug Targets Cardiovasc Haematol Disord,2003,3(1):31-57.
[73]王溪涛,刘波,张炎,等.低切应力对动脉粥样硬化血管平滑肌细胞Bcl-2和Bax蛋白表达的影响[J].解剖学报,2005,36(5):567-9.
[74] Bj?rkerud S, Bj?rkerud B, Joelsson M.Structural organization of reconstituted human arterial smooth muscle tissue.Arterioscler Thromb.1994 Apr;14(4):644-51.
[75] Han DK, Haudenschild CC, HongMK, et al. Evidence for apoptosis in human atherogenesis and in a rat vascular injurymodel[ J ]. Am J Pathol, 2003, 155 (2) : 267 - 77.
[76] David K, Han M, Handenschild CC , et al . Evidence for apoptosis in human atherosclerosis and in a rat vascular injury model . Am J Pathol ,1995 , 147 : 267 - 77
[77] Bennett M R ,Evan G I ,Schwartz S M. Apoptosis of human vascular smooth muscle cells deriverd from normal vessels and coronary atherosclerotic plaques [J ] . J Clin Invest , 1995 , 96(5) :2266– 74.
[78] Diez J , Panizo A. Is the regulation of apoptosis altered in smooth muscle cells of adult SHR[J ] Hypertens ,1997 ,29 :776.
[79]黄文新,阳跃忠,夏中华,等.色满卡林对自发性高血压大鼠血管平滑肌细胞凋亡的影响[J].中国新药与临床杂志,2006,25(6):401-4.
[80]周园,周家国,丘钦英,等.CIC-3氯通道对H2O2诱导的大鼠主动脉平滑肌细胞凋亡的影响[J].中国药理学通报,2006,22(10):1175-9.
[81] Hamet P , Richard L , Dam TV, et al .Apoptosis in target organs of hypertension[J].Hypertension ,1995,26:6421.
[82]余良生,化长林,黄碧兰,等.L-精氨酸对高血压大鼠主动脉平滑肌细胞凋亡的影响[J].咸宁学院学报:医学版2006,19(5):1175-9.
[83]景丽,张建中,秦璟,等.凋亡相关基因Bcl-6和Bax在高血压大鼠血管平滑肌细胞中的表达[J].宁夏医学院学报,2004,26(2):79-83.
[84] Inser JM,Kearney M,Bortman S ,et al . Apoptosis in human atherosclerosis and restenosis[J ] . Circulation ,1995 ,91(11) :2703.
[85] BauriedelG,HeidemannP,HeimerlJ,et al. Apoptosis inrest enosisver susstable- angina atherosclerosis. Arterioscler Thromb Vasc Biol,1998, 18:1132 -9.
[86] Kockx MM, DeMeyer GR, Muhring J, et al. Apotisis and related proteins in different stages of human atherosclerotic plaque [ J ].Circulation, 1998,97 (23) :237 - 9.
[87]李大勇,车艳,杨镛,等.腹主动脉瘤动脉壁血管平滑肌细胞增殖及凋亡的研究[J].中华普通外科杂志,2004,19(3):169-71.
[88] Fontaine V ,Jacob MP ,Houard X, et al . Involvement of the mural thrombus as a site of protease release and activation in human aortic aneurysms[J ] . Am J Pathol,2002 ,161 (5):1701-10.
[89]郭付有,宋来君,冯祖荫,等.流体切应力对大鼠血管平滑肌细胞凋亡的影响[J].中原医刊,2007,34(6):9-11.
[90] Saxena A, McMeekin JD, Thomson DJ. Expression of Bcl-x, Bcl-2, Bax, and Bak in endarterectomy and atherectomy specimens. J Pathol. 2002, 196(3):335-42
[91] Degterev A, Lugovskoy A, Cardone M, et al.Identification of small-molecule inhibitors of internation between the BH3 domain and Bcl-xL[J]. Nat Cell Biol, 2001,3(2):173- 82.
[92] Chiou FL,Chia LC,Chang WT,et al. Bcl-2 rescues ceramide and etoposide-induced mitochondrial apoptosis is through blockage of caspase-2 activation[J]. J Biol Chem,2005,280(25):23758- 65.
[93] Forte A, Galderisi U, De Feo M, et al. c-Myc antisense oligonucleotides preserve smooth muscle differentiation and reduce negative remodelling following rat carotid arteriotomy. J Vasc Res,2005,42(3):214-25.
[94] Jiang C,Yang YF,Cheng SH. Fas ligand gene therapyfor vascular intimal hyperplasia[J]. Curr Gene Ther,2004,4(1):33- 9.
[95] Matsumura ME,LI P,Berthoux L, et al. Vascular injury induces posttranscriptional regulation of the Id3 gene:cloning of a novel Id3 isoform expressed during vascular lesion formation in rat and human atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2001,21(5):752- 58.
[96]司艳红,王家富.动脉粥样硬化与平滑肌细胞凋亡的调控[J].中国临床康复,2005,9(47): 118-20.
[97] Prter,A.G.,Janicke,R.U. Emerging roles of caspase-3 in apoptosis. Cell Death Diff,1999,6:99-104.
[98] Zou,H. Li,Y. Liu,X.& Wang,X. An APAF-1 cytochrome c complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem,1999, 274:11549-56.
[99] Rdzanek A,Filipiak KJ,Karpinaki G,et al. Exercise urotensinⅡdynamics in myocardial infarction survivors with and without hypertension[J]. Peptides,2005,26(12): 2464-72.
[100] Stephen AD, Ohstein EH,Halawa N, et al. Congestive heart failure and expression of myocardial urotensinⅡinfusion in humans[J].Br J Clin Pharmacol, 2002,54(6):617-21.
[101]温进坤,韩梅.血管平滑肌细胞[M].北京:科学出版社,2005.
[102]刘红梅,黄体钢.血管平滑肌细胞的培养及其在血管疾病研究中的作用[J].实用心脑肺血管病杂志,2005,13(6):363-9
[103]彭黎明,王曾礼.细胞凋亡的基础与临床[M].北京:人民卫生出版社,2000.
[104]司徒镇强,吴军正.细胞培养[M].第二版.北京:世界图书出版社,2007.
[105]戴恩来,薛国忠,武俊斌,等.大鼠血管平滑肌细胞的贴块法培养[J].中医儿科杂志,2007,3(2):47-9
[106]陈焰炫、刘健康.动脉平滑肌细胞原代培养贴块法的改良[J].生物学杂志,2002,19(4):27-8.
[107]王伯沄,李玉松,黄高昇,等.病理学技术[M].北京:人民卫生出版社,2001.
[108] Rose R.Atherosolereosis-an inflammatory disease[J].N Eng J Med.1999,340(2):115- 26.
[109]沃兴德,丁志山.细胞凋亡与动脉粥样硬化[J].浙江中医学院学报,2001,25:76-7
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