尾加压素Ⅱ在大鼠动脉粥样硬化发病机制中的作用及Urantide的干预研究
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摘要
尾加压素Ⅱ(urotensin,UⅡ)是目前已知最强的缩血管活性肽,除血流动力学作用外,还具有非血流动力学作用,在多种疾病发生、发展中具有重要的病理生理学作用。特异性UⅡ受体拮抗剂的发展,可能使UⅡ成为某些疾病治疗的新靶点。
动脉粥样硬化(atherosclerosis,AS)是危害人类健康的常见疾病,人类死亡的头号杀手,因此AS发病机制和治疗对策的探究成为医学研究的热点。国内外大量的基础和临床研究均表明,UⅡ与AS的发生、发展有密切关系。Urantide是在离体主动脉研究中发现的最强选择性h UⅡ受体拮抗剂,但有关其在AS中的作用尚未见报道。
本研究应用形态学、生物化学、免疫细胞化学、免疫组织化学、流式细胞术、Western blot、RT-PCR等实验技术,通过体内、体外相互印证的方法,对比研究了AS大鼠胸主动脉及血管平滑肌细胞(VSMC)中UⅡ及其受体GPR14的变化、UⅡ与某些炎症介质之间的关系及对细胞外基质(ECM)的影响,旨在研究Urantide干预下UⅡ在大鼠AS发生、发展中的作用及其可能的作用机制。
体内实验结果表明,腹腔注射VD3 70 U/kg体重联合高脂饲料喂养4 W可成功复制大鼠AS模型,表现为胸主动脉出现典型的AS病变,胸主动脉UⅡ及其受体GPR14基因和蛋白表达水平增加,炎症介质C-反应蛋白(CRP)、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)及转化生长因子-β(TGF-β)表达增加;而Urantide则可改善AS大鼠的胸主动脉AS病变,减少UⅡ及其受体GPR14基因和蛋白的表达水平,下调炎症介质CRP及MCP-1的表达,并上调IL-6及TGF-β的表达。体外实验结果表明,UⅡ可促进大鼠VSMC增殖,上调VSMC中UⅡ及其受体GPR14基因和蛋白的表达,促进VSMC培养上清中CRP、MCP-I、IL-6、TGF-β及Ⅳ胶原(ColⅣ)的表达;而Urantide则能抑制大鼠VSMC增殖,下调VSMC中UⅡ及其受体GPR14基因和蛋白的表达,对VSMC培养上清中CRP、MCP-I、IL-6、TGF-β及ColⅣ均有不同程度的下调作用。
上述结果提示,UⅡ在AS发生、发展中发挥重要的作用,特异性UⅡ受体拮抗剂Urantide对大鼠AS有一定的保护作用,从而为Urantide临床应用治疗AS提供了理论基础。
Atherosclerosis (AS) is a systemic disease, mainly involving large and medium arteries, the basic lesion is intimal lipid deposition, intimal lesions like fibrosis ,and proliferation of smooth muscle cells and connective tissue, causing the formation of thickening fibrosis of intimal lesions and atheromatous plaque, which hardens arterial wall, narrows lumens and induces secondary lesions, especially ischemic lesions of organs such as heart and ischemic lesions. For a long time, there are a number of theories on AS pathogenesis, including lipid infiltration of theory、macrophage receptor absence of theory、thrombotic of theory、haemodynamics of theory、middle layer accrementition of contractile fiber cells of theory、endothelial cell injury theory, injury and inflammatory response theory. However, none of them can explain the origin and development of AS to the full extent. Therefore, AS pathogenesis and therapy of the inquiry are the hot point in medical research.
UⅡwas originally extracted from the tail spinal cord of fish pituitary, and shares its ubiquity in mollusks as well as mammals. GPR14, an isolated receptor and also a specific receptor of UⅡ, distributes mainly over the cardiovascular system. UⅡand GPR14 form UⅡ/UT system, triggering a series of biological effects, such as contraction of vascular function and promote mitogen effect. Lots of researches showed that UⅡplayed a important role in the homeostatic regulation of cardiovascular and the courses of the development of a disease. One of the main pathogenesis that bring about AS which may be the function of UⅡfunction in hemodynamics and the vascular wall and cells. Thus, the application of UⅡto preventing and curing AS which may has potential and important clinical value.
Urantide, a peptide receptor antagonist derived from the human being of UⅡ, has been the best UⅡof receptor antagonist, famous for its effect, 50～100 times than other compounds. The function of Urantide can be highly selective, for example, it only confronts vasoconstrictor effect induced by UⅡ, but not affecting norepinephrine, ET-1 and other effects caused by spasm. Experimental in vitro study of rat aorta, Urantide can be competitively antagonized UⅡ on contraction of rat thoracic aorta, and significantly inhibited UⅡinduced human monocyte- derived macrophage cholesterol acyltransferase activity increases-1, thereby preventing the formation of foam cells. At present, the domestic Urantide studies have focused on myocardial ischemic injury and vascular remodeling, the Urantide role in AS has not been reported.
In this study, morphology, biochemistry, immunocytochemistry, immunohistochemistry, flow cytometry, Western blot, RT-PCR and other techniques, through in vivo and in vitro methods confirmed the results, comparative the AS rat thoracic aorta and vascular smooth muscle cells (VSMC) in the UⅡand its receptor GPR14 changes, the relationship between UⅡand certain inflammatory mediators, and affected the extracellular matrix of the impact of the intervention to study under Urantide intervention , UⅡexisted the possible role and the mechanism of occurrance and development of AS in rats.
The main results are as follows:
(1) In vivo: AS group can be successfully replicated in rats, when VD3 70 U / kg was given by intraperitoneal injection,and fed with high fat diet during 4 W. The expression of Ca2 +, TG, TC, HDL and LDL in AS group were significantly higher than normal control group; and when we treated each group with Urantide,serum indicators were gradually decreased with the delivery time,catched or neared the level of positive control group. Control group were observed in rat thoracic aorta, the significant aortic intimal calcification, inflammatory cell infiltration, VSMC proliferation and foam-like cells, elastic fiber degeneration, fracture and collapse of the membrane atrophy, this was typical AS pathology; thoracic aorta UⅡand its receptor GPR14 gene and protein levels increased, the inflammatory mediators C-reactive protein (CRP) and monocyte chemoattractant protein-1(MCP-1) expression was increased, IL-6(IL-6) and transforming growth factor-β(TGF-β) expression was decreased; while Urantide treatment group increased with time, AS pathological changes gradually reduced, thoracic aorta pathology close to the positive group at 14 day in rats; reduction of UⅡand its receptor GPR14 gene and protein expression,will down regulated the levels of CRP and reduction of inflammatory mediators MCP-1 and up IL-6 and TGF-βexpression.
(2) In vitro: In this experiment, cultured VSMC as the object of study by UⅡstimulated VSMC proliferation, and then observed in the UⅡreceptor antagonist Urantide intervention, UⅡand its receptor GPR14 in VSMC and its possible mechanism. The results showed that, 10-8 mol/L UⅡat each time point could promote VSMC proliferation, cell cycle, so that the percentage of Sphase cells, PI and SPF were increased significantly promoted VSMC UⅡ, GPR14 gene and a large number of protein expression. Concentration in the range of 10-10～10-6, Urantide inhibited VSMC proliferation, inhibition of VSMC UⅡ, GPR14 gene and protein expression, 10-6 mol/L Urantide group had the most significant effect. These results suggest that, UⅡcan promote the VSMC mitogen role of rats, so that increased UⅡand its receptor GPR14 UⅡexpression; Urantide could antagonize UⅡpromote the role of VSMC mitogen, down UⅡand its receptor expression GPR14 UⅡ. From this we infer that, UⅡand its receptor GPR14 UⅡcan promote the occurrence , development of AS, and Urantide can block the process of AS .
The conclusions are as follows: 1. AS group can be successfully replicated in rats, when VD3 70 U / kg was given by intraperitoneal injection , and fed with high fat diet during 4 W;
2. UⅡand its receptor GPR14 gene and protein expressed a large number in AS rat thoracic aorta, Urantide can be down regulated UⅡ,its receptor GPR14 gene and protein expression;
3. UⅡcan promote inflammatory mediators CRP and MCP-1 expression, inhibited the expression of IL-6 and TGF-β; while inflammatory mediators CRP and MCP-1 expression are decreased treated by Urantide, increased the IL-6 and TGF-βexpression;
4. UⅡcan promote the proliferation of rat VSMC, increases in UⅡand its receptor GPR14 gene and protein expression; Urantide then could inhibit VSMC proliferation and lower VSMC in the UⅡand its receptor GPR14 gene and protein expression;
5. UⅡcan promote VSMC cultured supernatants of CRP, MCP-I, IL-6 and ColⅣexpression, Urantide can reduced CRP, MCP-I, IL-6 and ColⅣexpression;
The results provides a comprehensive,new experimental evidence for the treatment of AS. Urantide have a protective effect on AS, can reduce the symptoms of AS, therefore, expected to become a new target for clinical treatment of AS.
Innovation of this study: intraperitoneal injection of VD3 70 U/kg combined with high fat diet in 4 W, AS model can be successfully replicated in rats; the first time will be applied to rats Urantide AS study, certify that Urantide can down regulated the UⅡand its receptor GPR14 gene and protein expression of thoracic aorta and VSMC in rats, reducing inflammation, improving the AS lesions.
动脉粥样硬化(atherosclerosis,AS)是危害人类健康的常见疾病,人类死亡的头号杀手,因此AS发病机制和治疗对策的探究成为医学研究的热点。国内外大量的基础和临床研究均表明,UⅡ与AS的发生、发展有密切关系。Urantide是在离体主动脉研究中发现的最强选择性h UⅡ受体拮抗剂,但有关其在AS中的作用尚未见报道。
本研究应用形态学、生物化学、免疫细胞化学、免疫组织化学、流式细胞术、Western blot、RT-PCR等实验技术,通过体内、体外相互印证的方法,对比研究了AS大鼠胸主动脉及血管平滑肌细胞(VSMC)中UⅡ及其受体GPR14的变化、UⅡ与某些炎症介质之间的关系及对细胞外基质(ECM)的影响,旨在研究Urantide干预下UⅡ在大鼠AS发生、发展中的作用及其可能的作用机制。
体内实验结果表明,腹腔注射VD3 70 U/kg体重联合高脂饲料喂养4 W可成功复制大鼠AS模型,表现为胸主动脉出现典型的AS病变,胸主动脉UⅡ及其受体GPR14基因和蛋白表达水平增加,炎症介质C-反应蛋白(CRP)、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)及转化生长因子-β(TGF-β)表达增加;而Urantide则可改善AS大鼠的胸主动脉AS病变,减少UⅡ及其受体GPR14基因和蛋白的表达水平,下调炎症介质CRP及MCP-1的表达,并上调IL-6及TGF-β的表达。体外实验结果表明,UⅡ可促进大鼠VSMC增殖,上调VSMC中UⅡ及其受体GPR14基因和蛋白的表达,促进VSMC培养上清中CRP、MCP-I、IL-6、TGF-β及Ⅳ胶原(ColⅣ)的表达;而Urantide则能抑制大鼠VSMC增殖,下调VSMC中UⅡ及其受体GPR14基因和蛋白的表达,对VSMC培养上清中CRP、MCP-I、IL-6、TGF-β及ColⅣ均有不同程度的下调作用。
上述结果提示,UⅡ在AS发生、发展中发挥重要的作用,特异性UⅡ受体拮抗剂Urantide对大鼠AS有一定的保护作用,从而为Urantide临床应用治疗AS提供了理论基础。
Atherosclerosis (AS) is a systemic disease, mainly involving large and medium arteries, the basic lesion is intimal lipid deposition, intimal lesions like fibrosis ,and proliferation of smooth muscle cells and connective tissue, causing the formation of thickening fibrosis of intimal lesions and atheromatous plaque, which hardens arterial wall, narrows lumens and induces secondary lesions, especially ischemic lesions of organs such as heart and ischemic lesions. For a long time, there are a number of theories on AS pathogenesis, including lipid infiltration of theory、macrophage receptor absence of theory、thrombotic of theory、haemodynamics of theory、middle layer accrementition of contractile fiber cells of theory、endothelial cell injury theory, injury and inflammatory response theory. However, none of them can explain the origin and development of AS to the full extent. Therefore, AS pathogenesis and therapy of the inquiry are the hot point in medical research.
UⅡwas originally extracted from the tail spinal cord of fish pituitary, and shares its ubiquity in mollusks as well as mammals. GPR14, an isolated receptor and also a specific receptor of UⅡ, distributes mainly over the cardiovascular system. UⅡand GPR14 form UⅡ/UT system, triggering a series of biological effects, such as contraction of vascular function and promote mitogen effect. Lots of researches showed that UⅡplayed a important role in the homeostatic regulation of cardiovascular and the courses of the development of a disease. One of the main pathogenesis that bring about AS which may be the function of UⅡfunction in hemodynamics and the vascular wall and cells. Thus, the application of UⅡto preventing and curing AS which may has potential and important clinical value.
Urantide, a peptide receptor antagonist derived from the human being of UⅡ, has been the best UⅡof receptor antagonist, famous for its effect, 50～100 times than other compounds. The function of Urantide can be highly selective, for example, it only confronts vasoconstrictor effect induced by UⅡ, but not affecting norepinephrine, ET-1 and other effects caused by spasm. Experimental in vitro study of rat aorta, Urantide can be competitively antagonized UⅡ on contraction of rat thoracic aorta, and significantly inhibited UⅡinduced human monocyte- derived macrophage cholesterol acyltransferase activity increases-1, thereby preventing the formation of foam cells. At present, the domestic Urantide studies have focused on myocardial ischemic injury and vascular remodeling, the Urantide role in AS has not been reported.
In this study, morphology, biochemistry, immunocytochemistry, immunohistochemistry, flow cytometry, Western blot, RT-PCR and other techniques, through in vivo and in vitro methods confirmed the results, comparative the AS rat thoracic aorta and vascular smooth muscle cells (VSMC) in the UⅡand its receptor GPR14 changes, the relationship between UⅡand certain inflammatory mediators, and affected the extracellular matrix of the impact of the intervention to study under Urantide intervention , UⅡexisted the possible role and the mechanism of occurrance and development of AS in rats.
The main results are as follows:
(1) In vivo: AS group can be successfully replicated in rats, when VD3 70 U / kg was given by intraperitoneal injection,and fed with high fat diet during 4 W. The expression of Ca2 +, TG, TC, HDL and LDL in AS group were significantly higher than normal control group; and when we treated each group with Urantide,serum indicators were gradually decreased with the delivery time,catched or neared the level of positive control group. Control group were observed in rat thoracic aorta, the significant aortic intimal calcification, inflammatory cell infiltration, VSMC proliferation and foam-like cells, elastic fiber degeneration, fracture and collapse of the membrane atrophy, this was typical AS pathology; thoracic aorta UⅡand its receptor GPR14 gene and protein levels increased, the inflammatory mediators C-reactive protein (CRP) and monocyte chemoattractant protein-1(MCP-1) expression was increased, IL-6(IL-6) and transforming growth factor-β(TGF-β) expression was decreased; while Urantide treatment group increased with time, AS pathological changes gradually reduced, thoracic aorta pathology close to the positive group at 14 day in rats; reduction of UⅡand its receptor GPR14 gene and protein expression,will down regulated the levels of CRP and reduction of inflammatory mediators MCP-1 and up IL-6 and TGF-βexpression.
(2) In vitro: In this experiment, cultured VSMC as the object of study by UⅡstimulated VSMC proliferation, and then observed in the UⅡreceptor antagonist Urantide intervention, UⅡand its receptor GPR14 in VSMC and its possible mechanism. The results showed that, 10-8 mol/L UⅡat each time point could promote VSMC proliferation, cell cycle, so that the percentage of Sphase cells, PI and SPF were increased significantly promoted VSMC UⅡ, GPR14 gene and a large number of protein expression. Concentration in the range of 10-10～10-6, Urantide inhibited VSMC proliferation, inhibition of VSMC UⅡ, GPR14 gene and protein expression, 10-6 mol/L Urantide group had the most significant effect. These results suggest that, UⅡcan promote the VSMC mitogen role of rats, so that increased UⅡand its receptor GPR14 UⅡexpression; Urantide could antagonize UⅡpromote the role of VSMC mitogen, down UⅡand its receptor expression GPR14 UⅡ. From this we infer that, UⅡand its receptor GPR14 UⅡcan promote the occurrence , development of AS, and Urantide can block the process of AS .
The conclusions are as follows: 1. AS group can be successfully replicated in rats, when VD3 70 U / kg was given by intraperitoneal injection , and fed with high fat diet during 4 W;
2. UⅡand its receptor GPR14 gene and protein expressed a large number in AS rat thoracic aorta, Urantide can be down regulated UⅡ,its receptor GPR14 gene and protein expression;
3. UⅡcan promote inflammatory mediators CRP and MCP-1 expression, inhibited the expression of IL-6 and TGF-β; while inflammatory mediators CRP and MCP-1 expression are decreased treated by Urantide, increased the IL-6 and TGF-βexpression;
4. UⅡcan promote the proliferation of rat VSMC, increases in UⅡand its receptor GPR14 gene and protein expression; Urantide then could inhibit VSMC proliferation and lower VSMC in the UⅡand its receptor GPR14 gene and protein expression;
5. UⅡcan promote VSMC cultured supernatants of CRP, MCP-I, IL-6 and ColⅣexpression, Urantide can reduced CRP, MCP-I, IL-6 and ColⅣexpression;
The results provides a comprehensive,new experimental evidence for the treatment of AS. Urantide have a protective effect on AS, can reduce the symptoms of AS, therefore, expected to become a new target for clinical treatment of AS.
Innovation of this study: intraperitoneal injection of VD3 70 U/kg combined with high fat diet in 4 W, AS model can be successfully replicated in rats; the first time will be applied to rats Urantide AS study, certify that Urantide can down regulated the UⅡand its receptor GPR14 gene and protein expression of thoracic aorta and VSMC in rats, reducing inflammation, improving the AS lesions.
引文
[1] Conlon J, Yano K, Waugh D, et al. Distribution and molecular forms of urotensinⅡand its role in cardiovascular regulation in vertebrates [J]. J Exp Zool, 1996,275(2):226-238.
[2] Coulouarn Y, Lihrmann I, Jegou S, et al. Cloning of 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):15803-15808.
[3] Ames R, Sarau H, Chambers J K, et al. Human urotensinⅡis a potent vaso constrictor and agonist for the orphan receptor GPR14 [J]. Nature, 1999,401(6750):282-286.
[4] Behan D, Khongsaly O, Ling N, et al. Urocortin interaction with corticot ropinrleasing factor (CRF) binding protein (CRF-BP):A novol mechanism for elevating free CRF levels in human brain [J]. Brain Res, 1996,725(2):263-267.
[5] Matsushita M, Shichiri M, Imai T, et al. Coexp ressionof urotensinⅡand its receptor (GPR14) in human cardiovascular and renal tissues [J]. J Hypertens, 2001,19(12):2185-2190.
[6] Pearson D, Shively JE, Clark BR, et al. UrotensinⅡsomato statinlike peptide in the caudal neurosecretory system of fishes [J]. Proc NatlAcad Sci U S A, 1980,77(13):5021-5024.
[7] Liu Q, Pong S, Zeng Z, et al. Identification of urotensinⅡas the endogenous ligand for the orphan G2protein coupled receptor GPR14 [J]. Biochem Biophys Res Commun, 1999, 266(1): 174-178.
[8] Takahashi K, Totsune K, Murakami O, et al. Exp ressionof urotensinⅡand its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensinⅡ[J]. Pep tides, 2003,24(2):301-306.
[9] Watanabe T, Pakala R, Katagiri T, et al. Synergistic effect of urotensinⅡwith mildly oxidized LDL on DNA synthesis in vascular smooth muscle cells [J]. Circulation, 2001,104(12): 6-8.
[10]Conlon J, O’Harte F, Smith D, et al. Purification and characterization of urotensinⅡand parvalbumin from an elasmobranch fish [J]. Scyliorhinus canicula Neuroen-docrinology, 1992, 55(3):230-235.
[11]Maguire J, Kuc R, Davenport A. Orphan-receptor ligand human urotensinⅡ:receptorlocalization in human tissues and comparison of vasoconstrictor responses with endothelin-1 [J]. Br J Pharmacol, 2000,131(3):441-446.
[12]彭公永,冉丕鑫,钟南山.尾加压素Ⅱ生物学作用的研究进展[J].国外医学呼吸系统分册, 2003,23(4):183-185.
[13]Itoh H, McMaster D, Ledris K, et al. Function recepors for fish neuropiptide urotensinⅡin major rat arteries [J]. Eur J Pharmacol, 1998,149(2):61-66.
[14]Douglas S, Sulpizio A, Piercy V, et al. Differential vasoconstrictor activity of human urotensinⅡin vascular tissue isolated from the rat, mouse, dog, pig,marmoset and cynomolgus monkey [J]. Br J Pharmacol, 2000,131(7):1262-1274.
[15]黄虹.尾加压素Ⅱ心血管作用的细胞信号传导通路[J].国外医学、生理、病理科学与临床分册, 2003,23(4):344-347.
[16]Yano K, Hicks J, Vaudry H, et al. Cardiovascular actions of frog urotensinⅡin the frog, Rana catesbeiana [J]. Gen Comp Endocrinol, 1995,97(25):103-110.
[17]MacLean MR, Alexander D, Stirrat A, et al. Contractile responses to human urotensinⅡin rat and human pulmonary arteries:effect of endothelial factors and chronic hypoxia in the rat [J]. Br J Pharmacol, 2000,130(2):201-204.
[18]Hiller C, Berry C, Petrie M, et al. Effects of urotensinⅡin human arteries and veins of varying caliber [J]. Circulation, 2001,103(10):1378-1381.
[19]Bottill F, Douglas S, Hiley C, et al. Human urotinsinⅡis an endothelium-dependent vasodi- lator in ratsmall arteries [J]. Eur J Pharmacol, 2000,130(8):1865-1869.
[20]Katano Y,Ishihata A,Sharif I,et al. Vasodilator effect of urotensinⅡ,one of the most potentvasoconstrictor factors,on rat coronary arteries [J]. Eur.Pharmacol, 2000,402:5-7.
[21]Stirrat A, Gallagher M, Douglas S, et al. Potent vasodilator responses to human urotensinⅡIn human pulmonary andabdominal resistance arteries [J]. Circulation. 2001,3(2):1378-1381.
[22]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):147-150.
[23]高宇.人尾加压素Ⅱ与冠心病[J].吉林医学, 2006,27(1):103-105.
[24]张勇刚,齐永芬,夏春芳,等.尾加压素Ⅱ对血管平滑肌细胞殖的影响[J].中国药理学通报, 2001,17(2):155-157.
[25]Zou Y, Nagai R, Yamazake T, et al. UrotensinⅡinduces hypertrophic responses in cultured cardiomyocytes from neonatal rats [J]. FEBS Lett, 2001,508(1):57-61.
[26]WatanabeT, Takahashi K, Kanome T, et al. Human urotensinⅡpotentiates the mitogeni-ceffect of mildey oxidized low-density lipoprotein on vascular smooth muscle cells:comparison with other vasoactive agents and hydrogen peroxide [J].Hypertens Res,2006,29 (1):821-831.
[27]张超,谭敦勇. Urotensin-Ⅱ的研究进展[J]. Chinese Journal of Pathophysiology, 2002, 18(8): 1002-1006.
[28]Marchese A, Heiber M, Nguyen T, et al. Cloning and chromosomal mapping of Three novel genes GPR9,GPR10 and GPR14 encoding receptors related to inteRleukin,neuropeptide Y,and sommatostation receptor [J]. Genomic, 1995,29(23):335-344.
[29]Mori M, Sugo T, Abe M, et al. UrotensinⅡis the endogenous ligand of a G- protein coupled orphan receptor,SENR(GPR14) [J]. Biochem Biophys Res Commun, 1999, 265(1):123–129.
[30]Nothacker H, Wang Z, Mcneill A, et al. Identification ofthe natural ligand of an orphan G-protein-coupled receptor involved in the regulation of vasoconstriction [J]. Nat Cell Biol, 1999,1(6):383-385.
[31]Rakowski E, Hassan G, Dhanak D, et al. A role for urotensinⅡin restenosis following balloon angiop lasty:use of a selective GPR14 recep tor blocker [J]. Moll Cell Cardiol, 2005,39(5): 785-791.
[32]Behtn D, Herold C, Ohistein E, et al. Phannaeologieal charaeterization of SB-710411 Cpa- c[D-Cys-pal-D-Trp-Lys-val-cys]-Cpa-alnide,a novel PePtidie urotensin-ⅡrecePtor antagonist [J]. BrJPharmaeo, 2002,137(9):449-458.
[33]Camarda V, Guerrini R, Kostenis E, et al. A new ligand for the urotensinⅡreceptor [J]. Br J Phannaeo, 2002,137(7):311-314.
[34]Herold C, Behin D, Buekiey P, et al. The neuromedin B receptor antagonist,BIM-23127,is a Potent antagonist at human and rat urotensin-Ⅱreceptors [J]. Br J Phannaeol, 2003,39(6): 203- 207.
[35]Riccardo P, Paolo S, Sandro G, et al. Urantide:an ultrapotent urotensinⅡantagonist PePtide in the rat aorta [J]. Br J Pharmaco, 2003,40(23):1155-1158.
[36]Sidharta P, Wagner F, Bohnemeier H, et al. Phannacodynamics and phartnaco kineties ofthe urotensinⅡreceptor antagonist palosuran in macroalbuminuric diabetic Patienis [J]. Clin Phannacol Ther, 2006,80(1):246-256.
[37]Ross R. The pathogenesis of atherosclerosis, aperspective for the 1990s [J]. Nature, 1993,362 (29):801-809.
[38]梅美珍,徐也鲁,杨永宗(主编).动脉粥样硬化实验技术.中国病理生理学会动脉粥样硬化专业委员会, 1989,11:1-10.
[39]李才(主编).疾病模型与实验病理学.吉林大学出版社, 2002,82-83.
[40]杨小毅,万载阳,谭健苗,等.一种纯系小鼠动脉粥样硬化模型的建立[J].中国动脉硬化杂志, 1995,3(2):182-186.
[41]Groener J, Bax W, Stuani C, et al. Difference in substrate specificity between human and mouse lysosomal acid lipASe:low affinity for cholesteryl ester in mouse lysosomal acid lipASe [J]. Biochim Biophys Acta, 2000,1487(223):155-162.
[42]Tomkin G. Hyperglycaemia:the relation to dyslipidaemia and aterosclerosis [J]. Ir J Med Sci, 2002,171(3):161-164.
[43]张均田.现代药理实验方法.北京医科大学·中国协和医科大学出版社, 1998,1263-1271.
[44]Yang P, Rui Y, Li K, et al. Exp ression of intercellular adhension mo lecule-1 in U937 foam cells and the inh ibito ry effectof imperato rin [J]. Acta Pharmacol Sin, 2002,23(4):327- 330.
[45]杨鹏远,芮耀诚,张黎,等. U937泡沫细胞中血管内皮生长因子的表达及药物的抑制作用[J].药学学报, 2002,37(2):86-89.
[46]Yang P, Rui Y, Jin Y, et al. Antisense oligodeoxynucleo tide inh ibits vAScular endo thelial grow th facto r exp ression in U937 foam cells [J]. Acta Pharmacol Sin, 2003,24(6):610-614.
[47]Wissler R, Eilert M, Schroeder M, et al. Production of lipormatous and atheromatous arterial lesions in the albino rat [J]. Arch Pathol, 1954,57(9):333-341.
[48]成春英,何晓凡,孙勇,等.黄芎合剂对高脂血症大鼠动脉粥样硬化形成的影响[J].医学临床研究, 2006,23(4):468-470.
[49]王禄增,张梅英,季勇,等.脂蛋白a与动脉粥样硬化的研究进展[J].中国实验动物学报, 2002,10(2):113-115.
[50]Schmid K, M cshary W, Pameijer C, et al. Chemical and physiochemical studies on themineral deposits of the humanathero sclerosis aorta [J]. Atherosclerosis, 1980,37(3): 199-208.
[51]Fleckenstein-Grun G, Frey M, Luley C, et al. Differentiation calcium and choles teroldomin -ated types of atherosclerosis lesion:antiar-teriosclerotic Aspects of calcium antagonist [J]. Cardiov AS Pharm acol, 1991,18(16):1-9.
[52]焦宏,陈彦静.大鼠动脉粥样硬化模型的建立[J].河北北方学院学报, 2009,26(6):66-67.
[53]Weinstein D, Heider J. Antiatherogenic Properties of Calcium antagonists determinants [J]. Am J Cardiol, 1987,59(1):163-172.
[54]孙安阳,俞彰,钟慈声,等.大鼠动脉钙超负荷模型的建立及确证[J].中华医学杂志, 1999,79(10):769-772.
[55]Kramsch D. Atherosclerosis progression/regression:lipoprotein and vessel wall [J]. Atherscl- erosis, 1995,118(1):29-36.
[56]Price P, June H, Buckley J, et al. Osteop rotegerin inhibits artery Calcigfication induced bywarfarin and by vitamin D [J]. Arterioscler Thromb VASc Biol, 2001,21(17):1610-1616.
[57]吴开云,高摄渊,袁融,等.维生素D诱发大鼠动脉粥样硬化的实验研究[J].解剖学报, 1996,27(2):133-135.
[58]沈丽,卢维晟,姚俊宇,等.不同方法建立动脉粥样硬化大鼠模型的比较[J].心脏杂志, 2005, 17(1):18-20.
[59]杨鹏远,芮耀诚,焦亚斌,等.动脉粥样硬化大鼠实验模型的建立[J].第二大军医大学学报, 2003,24(7):802-804.
[60]温进坤,韩梅,杜玮南,等.一种快速建立大鼠动脉粥样硬化模型的实验方法[J].中国老年学杂志, 2001,21(1):50-51.
[61]郭延松,杨军珂.鼠动脉粥样硬化模型的建立[J].中国动脉粥样硬化杂志, 2003,11(1): 84-86.
[62]郭延松,吴宗贵,杨军珂,等.三种大鼠动脉粥样硬化模型复制方法的比较[J].中国动脉粥样硬化杂志, 2003,11(5):465-469.
[63]Sasaki S, Yoneda Y, Fujita H, et al. Asociation of blood pressure variability with induction of atherodclerosis in cholesterol-fed rats [J]. Am J Hypertens , 1994,7(5):453-459.
[64]张磊,陈国荣,郑荣远,等.高脂饲料加空气干燥术建立兔颈动脉粥样硬化模型[J].中国动脉硬化杂志, 2002,9(2):155-158.
[65]彭侃夫,孟建中,吴宗贵,等.苯那普利对家兔动脉粥样硬化形成和斑块破裂的作用[J].第二军医大学学报, 2003,24(7):798-801.
[66]Misra P, Sriv S, Singhal S, et al. Glutathione s-transferASe8-8 is localized in smooth muscle cells of rat aorta and induced in an experimental model of atherosclerosis [J]. Toxicol Appl Pharmacol, 1995,33(1):27-33.
[67]Span A, Grauls G, Bosman F, et al. Cytomegalovirus infection induces AS cular injury in the rat [J]. Atherosclerosis, 1992,93(122):41-52.
[68]Castellanos E, Sueishi K, Tanaka K, et al. Ultrastructural studies of rat arteriosclerosis induced by stimulation of the immune system with ovalbumin [J]. Acta Pathol J PN, 1991, 41(2): 113- 121.
[69]Mennander A, Tiisala S, Halttunen J, et al. Chronic rejection in rat aortic allografts.An exp- erimental model for transplant arteriosclerosis [J]. ArteriosclerThromb, 1991,11(4): 671-680.
[70]Cramer D, Chapman F, Wu G, et al. Cardiac transplantation in the rat,Alteration of the severity of donor graft arteriosclerosis by modulation of the host immune response [J]. Trans- plantation, 1990,50(3):554-558.
[71]李玉琳.分子病理学.人民卫生出版社, 2002,325-327.
[72]李建军,李庚山,黄从新,等.球囊损伤兔主动脉后核因子κB活性的动态变化[J].中国动脉硬化杂志, 2001,9 (1):34-36.
[73]卢次勇,凌文华,马静,等. ERK1/2在氧化型低密度脂蛋白诱导血管平滑肌细胞增殖中的作用[J].中国公共卫生, 2002,18(11):1286-1288.
[74]Lin G. Insights of high-density lipoprotein-mediated lipid ef-flux from cells [J]. Biochem Biophys ResCommun, 2002,291(4):727-73l.
[75]Shaul P. Endothelial nitric oxide synthase,caveolae and the development of atherosclerosis [J]. J Physio, 2003,547(1):21-33.
[76]山丽梅,张锦超,汪海,等.血管内皮细胞功能与动脉粥样硬化关系的研究进展[J].解放军药学学报, 2002,18(5):294-297.
[77]Furchgott R, Zawadzki J. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine [J]. Nature, 1980,288(5789):373-379.
[78]朱妙章,袁文俊,吴博威,等.心血管生理学与临床[J].高等教育出版社, 2004,152-153.
[79]温进坤,韩梅.血管平滑肌细胞[J].科学出版社, 2005,1-2.
[80]刘红梅,黄体钢.血管平滑肌细胞的培养及其在心血管疾病研究中的应用[J].实用心脑肺血管病杂志, 2005,13(6):364-368.
[81]王海燕,贾国良,张荣庆,等.人脐静脉内皮细胞共培养的人脐动脉平滑肌细胞生物学特性研究[J].中国临床康复, 2004,8(12):2258-2259.
[82]庄瑜,刘俊,肖明.血管平滑肌细胞在动脉粥样硬化中的作用[J].现代生物医学进展, 2009, 9(17):3375-3377.
[83]Schaub F, Han D, Liles W, et al. Fas/FADD mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells [J]. Nat Med, 2000, 6(7) 790- 796.
[84]Rensen S, Doevendans P, Van E, et al. Regulation and characteristics of Vascular smooth muscle cell phenotypic diversity [J]. Netherlands Heart J, 2007,15(3):100-108.
[85]王生兰,苏娟,徐一洲,等.大鼠血管平滑肌细胞体外培养的表型转换及其鉴定[J].中国动脉粥样硬化杂志, 2008,16(4):268-272.
[86]Libby P, Ridker P. Novel inflammatory markers of coronrisk:theory versusPraetiee [J]. Cireula- tion, 1999,100(1):148-1150.
[87]Albert C, Ma J, Fai N, et al. ProsPeetivestudy of C-reaetiveProtein,homoeyste Ine,andplas- matic levels as predietors of sudden cardiae death [J]. Cireulation, 2002,105(48):2595-2599.
[88]Libby P, Aikaw A. Stabilization of atheroselerotie plaques:new meehanisms and clinieal targets [J]. Nature Med, 2002,8(1):1257-1262.
[89]梁克山,谭兰. C反应蛋白与动脉粥样硬化性疾病[J].山东医学高等专科学校学报, 2006,28(2):135-139.
[90]Ridker P, Stampfer M, Rifai N, et al. Novel risk factors for systemic atherosclerosisa comp-areison of C-reactive protein, fibrinogen, homocysteine, lipoprotein,and standard cholesterol scrning predictors of peripheral arterial disease [J]. JA MA, 2001,285(12): 2481-2485.
[91]李志勇,李勋. C反应蛋白与冠状动脉粥样硬化性心脏病[J]. Medical Recap itulate, 2008, 14(23):3580-3585.
[92]Bang R, Marnell L, Mold C, et al. Analysis of binding sites in human C-reaetive Protein for Fe{gamma}RI,Fe{gamma}RllA,and Clq bysite-direete Mutagenesis [J]. J Biol Chem, 2005,280 (112):25095-25102.
[93]陈成,陈金水. C反应蛋白在动脉粥样硬化形成中的机制[J].中西医结合心脑血管病杂志, 2006,4(10):894-896.
[94]潘巍巍,江珊.超敏C反应蛋白与动脉粥样硬化的研究进展[J].中国心血管病研究, 2007,5(12):940-943.
[95]Lagrand W, Niessen H, Wblbink G, et al. C-reactive protein colocalizes with complement in human hearts during acute myoeardial infarction [J]. Cireulation, 1997,95(1):97-103.
[96]Li J, Fang C. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular disease [J]. Med Hypotheses, 2004,62(3):499-506.
[97]Reynolds G, Vance R. C-reactive protein immunohistochemical localization in nomal and atherosclerotic human aortas [J]. ArchPathol LabMed, 1987,111(2):265-269.
[98]Hatanaka K, Li X, Masuda K, et al. Immunohistochemical localization of C-reactive protein binding sites in human aortic lesions by a modified strep tavidin-biotin-staining method [J]. Pathol Int, 1995,45(6):635-641.
[99]Pasceri V, Willerson J, Yeh E, et al. Direct proinflammatory effect of C-reactive protein on human endothelial cells [J]. Circulation, 2000,102(8):2165-2168.
[100]Wang C, Li S, Weisel R, et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smoot h muscle [J]. Circulation, 2003,107(13):1783-1790.
[101]林杨,叶山东.单核细胞趋化蛋白-1与糖尿病动脉粥样硬化的关系.国际内科学杂志, 2007,34(7):381-385.
[102]徐梦丹,戴秋艳,孙宝贵.单核细胞趋化蛋白-1及受体在血管紧张素Ⅱ诱导的血管病变中的作用[J].心血管病学进展, 2006,27(4):505-508.
[103]王国平,邓仲端,瞿智玲.氧化修饰的低密度脂蛋白和极低密度脂蛋白对单核细胞MCP-1表达的影响[J].中华病理学杂志, 1996,25(4):220-223.
[104]王国平,邓仲端,瞿智玲.氧化修饰的极低密度脂蛋白对单核细胞趋化蛋白-1 mRNA表达的影响[J].中国病理生理杂志, 1997,13(2):114-117.
[105]王国平,邓仲端,瞿智玲.氧化修饰的低密度和极低密度脂蛋白对巨噬细胞单核趋化蛋白表达的影响[J].中华医学杂志, 1997,77(3):212-215.
[106]于光耀,邓仲端,瞿智玲.氧化修饰脂蛋白对内皮细胞单核细胞趋化蛋白-1表达的影响[J].中华病理学杂志, 1998,27(3):174-176.
[107]Frazier Jessen M, Kovacs E, et al. Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages [J]. J Immunol, 1995,154(4):1838- 1845.
[108]Klouche M, Gottschling S, Gerl V, et al.Atherogenic properties of enzy-matically degraded LDL:selective induction of MCP-1 and cytotoxic ef-fects on human macrophages [J]. Arterioscler Thromb Vasc Biol, 1998,18(9):1376-1385.
[109]Zeiher AM, Fisslthaler B, Schray B, et al. Nitric oxide modulates theexpressionof monocyte chemoattractant protein 1 in cultured human eothendilial cells [J]. CircRes, 1995, 76(6): 980-986.
[110]Weisberg S, Hunter D, Huber R, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding [J]. J Clin Invest, 2006,116(1):115-124.
[111]Viedt C, Vogel J, Athanasiou T, et al. Monocyte chemoattractant protein-1 induces prolife- ration and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-kappa B and activator protein-1 [J]. Arterioscler Thromb Vasc Biol, 2002,22 (6):914-920.
[112]陈志伟,李胜涛,陈琪,等.白细胞介素-6、白细胞介素-10与冠心病关系的研究进展[J].中西医结合心脑血管病杂志, 2008,6(8):949-951.
[113]Zhang P, Levy A, Ben-Simchon L, et al. Induction of neuronal and myelin-related gene expression by IL-6-receptor/IL-6:a study on embryonic dorsal root ganglia cells and isolated Schwann cells [J]. ExpNeurol, 2007,208(2):285-296.
[114]Soygur H, Palaoglu O, Akarsu E, et al. Interleukin-6 levels and HPA axis activation in breast cancer patients with major depressive disorder [J]. Prog Neuropsychopharmacol Biol Psychiatry,2007,31(6):1242-1247.
[115]Naya M, Tsukamoto T, Morita K, et al. Plasma interleukin-6 and tumor necrosis factor- alpha can predict coronary endothelial dysfunction in hypertensive pat inepts [J]. Hyperte- nsRes, 2007,30(6):541-548.
[116]Huber S, Sakkinen P, Conze D, et al. Interleukin-6 exacerbates early atherosclerosis in mice [J]. Arterioscler Thromb Vasc Biol, 1999,19(14):2364-2367.
[117]刘晓柳,李光千.白介素-6及其受体与心血管系统的研究进展[J].细胞分子与免疫学杂志, 2009,25(2):189-191
[118]张占彬.动脉粥样硬化中白细胞介素的研究进展[J]. Gan su Science and Technology, 2003,19(10):134-135.
[119]Wassmann S, Stumpf M, Strehlow K, et al. Interleukin-6 induces oxidative stress and endo- thelial dysfunction by overexpression of the angiotensinⅡtype1 receptor [J]. Circ Res, 2004,94(3):534-541.
[120]Baburhan G, Sibel G, Burhan T, et al. The roles of oxidized low-density lipoprotein and interleukin-6 levels in acute atheroma thrombotic and lacunar ischemic stroke [J].Angiology, 2008,59(1):224-229.
[121]刘娟,陈丽琴,陈丽琴,等.人冠状动脉粥样硬化斑块内白细胞介素6和18及肿瘤坏死因子-α表达与斑块稳定性有关[J].中国动脉硬化杂志, 2008,6(7):537-540.
[122]Tilg H, Trehu E, Atkins M, et al. Interleukin-6 as an anti-inflammatory cytokine:induction of circulating IL-1receptor antagonist and soluble tumor necrosis factor receptor p55 [J]. Blo- od, 1994,83(1):113-118.
[123]Liao H, Matsumoto A, Itakura H, et al. Transcriptional inhibition by interleukin-6 of the class a macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line [J]. Arterioscler Thromb Vasc Biol, 1999,19(13): 1872-1880.
[124]张恺芳,田英.转化生长因子β在动脉粥样硬化中的作用研究进展[J].中国动脉硬化杂志, 2006,14(7):636-638.
[125]胡艺琼,刘先哲.转化生长因子β对动脉粥样硬化中血管平滑肌细胞的作用及其影响[J].时珍国医国药, 2008,19(1):167-169.
[126]郑琼莉,祝炜,贾晶,等.转化生长因子β1与心血管疾病[J].中国心血管病研究杂志, 2006,4(7):550-551.
[127]梅卫义,杜志民,陈国伟.转化生长因子-β与冠心病[J].国外内科学分册, 2005,32(2): 70-74.
[128]Massague J, Chen Y. Controlling TGF-βsignalling [J]. Gene Dev, 2000,14(3):627-632.
[129]Blobe G, William P. chiemann,Harvey FLodish,Role of transforming growth factorβin human disease [J]. N Engl J Med, 2000,342(275):1350-1357.
[130]金炜,董维平,杨红,等.转化生长因子β1在动脉粥样硬化形成中的作用及机制研究[J].中国药理学通报, 2003,19(6):650-653.
[131]Grainger D, Mosedale D, Metcalfe J, et al. Dietary fat and reduced levels of TGF beta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions [J]. J Cell Sci, 2000,113(8):2355-2361.
[132]DingA, Nathan C, Graycar J, et al. Macrophage deactivating factor and trans-forming growth factors-β1-β2 and-β3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-γ[J]. J Immunol, 1990,145(11):1940-1944.
[133]Lutgens E, Gijbels M, Smook M, et al. Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression [J]. Arteriosclerosis Thromb Vasc Biol, 2002,22(5):975-982.
[134]Camarda V, Rizzi A, Calo G, et al. Effects of human urotensinⅡin isolated vessels of various species:comparison with other vasoactive agents [J]. Naunyn Schmiedebergs Arch Pharmacol, 2002,365(1):141-149.
[135]Rossowski W, Cheng B, Taylor J, et al. Human urotensinⅡinduced aorta ring contractions are mediated by protein kinase C,tyrosine kinases and Rho-kinase:inhibition by somatos tatin receptor antagonists [J]. Eur JPharmacol, 2002,435(3):159-170.
[136]Bottrill F, Douglas S, Hiler C, et al. Human urotensinⅡis an endothelium -dependent vasodilator in rat small arteries [J]. Br J Pharmacol, 2001,130(8):1865-1870.
[137]Ishihata A, Sakai M, Katano Y, et al. Vascular contractile effect of urotensinⅡin young and aged rats:influence of aging and contribution of endothelial nitric oxide [J]. Peptides, 2006, 27(1):80-86.
[138]张丽芳,陈莉,丁文惠,等.血浆尾加压素Ⅱ浓度与冠状动脉病变程度的关系[J].中日友好医院学报, 2008,22(1):3-5.
[139]李康,丁文惠,史力斌,等.尾加压素Ⅱ对大鼠胸主动脉球囊损伤后血管重塑的作用[J].中国病理生理杂志, 2008,24(4):674-679.
[140]Bousette N, Patel L, Douglas S, et al. Increased expression of urotensinⅡand its cognate recep tor GPR14 in atherosclerotic lesions of the human aorta [J]. Atherosclerosis, 2004,176 (6):117-123.
[141]Vincent S, Erik L, Jacques B, et al. Human urotensinⅡinduced contraction and arterial smooth muscle cell proliferation are mediated by rhoA and rhokinase [J]. Circulation Res, 2001, 88(45):1102-1104.
[142]唐朝枢,刘秀华.细胞外信号引起核反应的细胞信号转导途径[J].药理学进展, 1998 (1):72-85.
[143]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):155-157.
[144]彭旭,尹航,汪丽蕙,等.尾加压素Ⅱ增加血管平滑肌细胞粘着斑激酶的含量和活力[J].生理学报, 2000,52(6):455-458.
[145]齐永芬,卜定方,牛大地,等.尾加压素Ⅱ促进大鼠血管平滑肌细胞内皮素生成[J].科学通报, 2002,47(4):289-292.
[146]任安经,林丽,袁文俊.尾加压素Ⅱ—促细胞增殖的活性肽[J].心脏杂志, 2004,16 (6):572- 574.
[147]Watanabe T, Takahashi K, Kanome T, et al. Human urotensinⅡpotentiates the mitogenic effect ofmildly oxidized low density lipo protein on vascular smooth muscle cells:com- parison,with other vasoactive agents and hydrogen peroxide [J]. Hypertens Res, 2006, 29(4): 821-831.
[148]Wang Y, Ding Y, Zhu Y, et al. Role of PKC in the novel synergistic action of urotensinⅡand angitensinⅡand in urotensinⅡinduced vasoconstriction [J]. Am J Physiol Heart Circ Physiol, 2007,292(2):348-359.
[149]Camarda V, Song W, Marzola, et al. Urantide mimies urotensin-Ⅱinducede ale-ium release in cells expressing reeombinant UT reeePtors [J]. EurJ Phannaeo, 2004,498(1):83-86.
[150]Dhanak D, Kllight S, et al. Sulfonamide derivative urotensinⅡreceptor anta-gonists, preparation,Pharlnaceutieal compositions,and therapeutie use [J]. PCT Int APP, 2001, 598 (2): 283-286.
[151]Valeria C, Martina S, Wei S, et al. In vitro and in vivo pharmacological Chara-cterizationof the novel UT receptor ligand[Pen5,DTrp7,Dab8]urotensin (4–11)(UFP-803) [J]. British Journal of Pharmacology, 2006,147(1):92-100.
[152]Johns D, Gao Z, Naselsky D, et al. UrotensinⅡImediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators [J]. Naunyn Schmiedebergs Arch Pharmacol, 2004,370(4):238-250.
[153]姚华,陈志武. Urantide对实验性心肌缺血及缺氧再给氧损伤的影响[J].安徽医科大学学报, 2008,3(2):294-296.
[154]赵娟,任立群. VD3联合高脂饲料建立大鼠动脉粥样硬化模型[J].实用医学杂志, 2009,25 (21):3569-3571.
[155]Shi L, Ding W, Li D, et al. Proliferation and anti-apop totic effects of human urotensinⅡon human endothelial cells [J]. Atherosclerosis, 2006,188(2):260-264.
[156]Sauzeau V, LeMellionnec E, Bertoglio J, et al. Human urotensinⅡinduced contraction and arterial smooth muscle cell proliferationare mediated by RhoA and Rho-Kinase [J]. Circ Res, 2001,88(67):1102-1104.
[157]Matsusaka S, Wakabayashi I. Enhancement of vascular smooth muscle cellmigration by urotensinⅡ[J]. Naunyn Schmiedebergs Arch Pharmacol, 2006,373(2):381-386.
[158]Claesson Welsh L. Signal transduction by vascular endothelial growth factor receptors [J]. Biochem Soc Trans, 2003,31(1):20-24.
[159]司徒振强,吴军正.细胞培养.世界图书出版公司, 2004,245.
[160]Bousette N, Patel L, Douglas S, et al. Increased exp ression of urotensinⅡand its cognate reeptor GPR14 in atherosclerotic lesions of the human aorta [J]. Atherosclerosis, 2004,176 (1): 117-123.
[161]李立.维持血液透析患者微炎症状态与血管通路功能丧失的相关性研究[J].东南大学硕士, 2006,34.
[162]Penn M, Topoi E. Tissue factor,the emerging link between inflammation,thrombosis and vascular remodeling [J]. Cir Res, 2001,89(1):1-2.
[163]Yaso JimaK, Sehwab C, Ger E, et al. Generation of C-reactive protein and complement components in atherosclerotic plaques [J]. Am J Pathol, 2001,158(34):1039-1051.
[164]Tomai F, Crea F, Gaspardone A, et al. Unstable angina and Elevated C-reactive protein levels predict enhanced vasoreactivity of the eu1prit lesion [J]. Cireulation, 2001,104(74): 1471-1476.
[165]Paseeri V, Willersn T, Yeh T, et al. Direet proinflammatory effect of C-reaetive Protein on human endothelial cells [J]. Circulation, 2000,102(234):2165-2168.
[166]Fiehtlseherer S, Rosenberger G, Walter H, et al. Elevated C-reactive protein Levels and impaired endothelial vasoreactivity in patients with coronary artery Disease [J]. Cireulation, 2000,102(43):1000-1043.
[167]Boos J, Lip G. .Elevated high-sensitive C-reactive Protein,large arterial Stiffness and atherosclerosis:arelationship between inflammation and hypertension.Journal of Human [J].Hypertension, 2005,19(5):511-516.
[168]Bisoendial J, Kastelein J, Levels H, et al. Aetivation of inflammation and Coagulation after infusion of C-reactive protein in humans [J]. Cire Res,2005,96(6):714-716.
[169]Yu X, Dluz S, Graves T, et al.Elevated expression of monocyte chemoattractant Protein-1 by vascular smooth muscle cells in hypercholesterolemic p rimates [J]. Proc Natl Acad Sci USA, 1992,89:6953-6957.
[170]Weber C, Schober A, Zernecke A, et al. Chemokines key regulators of mononuclear cell recruitment in atherosclerotic vascular disease [J]. Arterioscler Thromb Vasc Biol,2004,24 (9): 1997-2008.
[171]Rus G, Vlaicu R, Niculescu F, et al. Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall [J]. Atherosclerosis, 1996,127(2):263-271.
[172]潘晓宏,单江,罗建红,等.碱性成纤维细胞生长因子和白细胞介素-6促进大鼠血管平滑肌细胞增殖的协同作用[J].中国动脉硬化杂志, 2000,8(3):233-235.
[173]Kranzhofer R, Clinton S, Ishii K, et al. Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes [J]. Circ Res, 1996, 79(2):286-294.
[174]Piek E, Heldin C, Dij P, et al. Specificity,diversity,and regulation in TGF-βsuperfamily signaling [J]. FASEB J, 1999,13(436):2015-2212.
[175]Argmann C, Diepstraten C, Sawyez C, et al. Transforming growth factor-beta1 inhibitsmacrophage cholcsteryl ester accumulation induced by native and oxidized VLDL rem- nants [J]. Arterioscler Throm Vasc Bio, 2001,21(12):2011-2018.
[176]赵贞,吴金玉.Ⅳ型胶原在糖尿病肾病中的作用[J].深圳中西医结合杂志, 2009,19(2): 121-123.
[177]杨方,赵培真.胶原与动脉粥样硬化[J].中国动脉硬化杂志, 1996,4(3):226-229.
[178]Tanimura A, MeGregor D, Amderson H, et al. Calcification in atherosclerosis:Human studies [J]. J Exp Pathol, 1986,5(1):261-273.
[2] Coulouarn Y, Lihrmann I, Jegou S, et al. Cloning of 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):15803-15808.
[3] Ames R, Sarau H, Chambers J K, et al. Human urotensinⅡis a potent vaso constrictor and agonist for the orphan receptor GPR14 [J]. Nature, 1999,401(6750):282-286.
[4] Behan D, Khongsaly O, Ling N, et al. Urocortin interaction with corticot ropinrleasing factor (CRF) binding protein (CRF-BP):A novol mechanism for elevating free CRF levels in human brain [J]. Brain Res, 1996,725(2):263-267.
[5] Matsushita M, Shichiri M, Imai T, et al. Coexp ressionof urotensinⅡand its receptor (GPR14) in human cardiovascular and renal tissues [J]. J Hypertens, 2001,19(12):2185-2190.
[6] Pearson D, Shively JE, Clark BR, et al. UrotensinⅡsomato statinlike peptide in the caudal neurosecretory system of fishes [J]. Proc NatlAcad Sci U S A, 1980,77(13):5021-5024.
[7] Liu Q, Pong S, Zeng Z, et al. Identification of urotensinⅡas the endogenous ligand for the orphan G2protein coupled receptor GPR14 [J]. Biochem Biophys Res Commun, 1999, 266(1): 174-178.
[8] Takahashi K, Totsune K, Murakami O, et al. Exp ressionof urotensinⅡand its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensinⅡ[J]. Pep tides, 2003,24(2):301-306.
[9] Watanabe T, Pakala R, Katagiri T, et al. Synergistic effect of urotensinⅡwith mildly oxidized LDL on DNA synthesis in vascular smooth muscle cells [J]. Circulation, 2001,104(12): 6-8.
[10]Conlon J, O’Harte F, Smith D, et al. Purification and characterization of urotensinⅡand parvalbumin from an elasmobranch fish [J]. Scyliorhinus canicula Neuroen-docrinology, 1992, 55(3):230-235.
[11]Maguire J, Kuc R, Davenport A. Orphan-receptor ligand human urotensinⅡ:receptorlocalization in human tissues and comparison of vasoconstrictor responses with endothelin-1 [J]. Br J Pharmacol, 2000,131(3):441-446.
[12]彭公永,冉丕鑫,钟南山.尾加压素Ⅱ生物学作用的研究进展[J].国外医学呼吸系统分册, 2003,23(4):183-185.
[13]Itoh H, McMaster D, Ledris K, et al. Function recepors for fish neuropiptide urotensinⅡin major rat arteries [J]. Eur J Pharmacol, 1998,149(2):61-66.
[14]Douglas S, Sulpizio A, Piercy V, et al. Differential vasoconstrictor activity of human urotensinⅡin vascular tissue isolated from the rat, mouse, dog, pig,marmoset and cynomolgus monkey [J]. Br J Pharmacol, 2000,131(7):1262-1274.
[15]黄虹.尾加压素Ⅱ心血管作用的细胞信号传导通路[J].国外医学、生理、病理科学与临床分册, 2003,23(4):344-347.
[16]Yano K, Hicks J, Vaudry H, et al. Cardiovascular actions of frog urotensinⅡin the frog, Rana catesbeiana [J]. Gen Comp Endocrinol, 1995,97(25):103-110.
[17]MacLean MR, Alexander D, Stirrat A, et al. Contractile responses to human urotensinⅡin rat and human pulmonary arteries:effect of endothelial factors and chronic hypoxia in the rat [J]. Br J Pharmacol, 2000,130(2):201-204.
[18]Hiller C, Berry C, Petrie M, et al. Effects of urotensinⅡin human arteries and veins of varying caliber [J]. Circulation, 2001,103(10):1378-1381.
[19]Bottill F, Douglas S, Hiley C, et al. Human urotinsinⅡis an endothelium-dependent vasodi- lator in ratsmall arteries [J]. Eur J Pharmacol, 2000,130(8):1865-1869.
[20]Katano Y,Ishihata A,Sharif I,et al. Vasodilator effect of urotensinⅡ,one of the most potentvasoconstrictor factors,on rat coronary arteries [J]. Eur.Pharmacol, 2000,402:5-7.
[21]Stirrat A, Gallagher M, Douglas S, et al. Potent vasodilator responses to human urotensinⅡIn human pulmonary andabdominal resistance arteries [J]. Circulation. 2001,3(2):1378-1381.
[22]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):147-150.
[23]高宇.人尾加压素Ⅱ与冠心病[J].吉林医学, 2006,27(1):103-105.
[24]张勇刚,齐永芬,夏春芳,等.尾加压素Ⅱ对血管平滑肌细胞殖的影响[J].中国药理学通报, 2001,17(2):155-157.
[25]Zou Y, Nagai R, Yamazake T, et al. UrotensinⅡinduces hypertrophic responses in cultured cardiomyocytes from neonatal rats [J]. FEBS Lett, 2001,508(1):57-61.
[26]WatanabeT, Takahashi K, Kanome T, et al. Human urotensinⅡpotentiates the mitogeni-ceffect of mildey oxidized low-density lipoprotein on vascular smooth muscle cells:comparison with other vasoactive agents and hydrogen peroxide [J].Hypertens Res,2006,29 (1):821-831.
[27]张超,谭敦勇. Urotensin-Ⅱ的研究进展[J]. Chinese Journal of Pathophysiology, 2002, 18(8): 1002-1006.
[28]Marchese A, Heiber M, Nguyen T, et al. Cloning and chromosomal mapping of Three novel genes GPR9,GPR10 and GPR14 encoding receptors related to inteRleukin,neuropeptide Y,and sommatostation receptor [J]. Genomic, 1995,29(23):335-344.
[29]Mori M, Sugo T, Abe M, et al. UrotensinⅡis the endogenous ligand of a G- protein coupled orphan receptor,SENR(GPR14) [J]. Biochem Biophys Res Commun, 1999, 265(1):123–129.
[30]Nothacker H, Wang Z, Mcneill A, et al. Identification ofthe natural ligand of an orphan G-protein-coupled receptor involved in the regulation of vasoconstriction [J]. Nat Cell Biol, 1999,1(6):383-385.
[31]Rakowski E, Hassan G, Dhanak D, et al. A role for urotensinⅡin restenosis following balloon angiop lasty:use of a selective GPR14 recep tor blocker [J]. Moll Cell Cardiol, 2005,39(5): 785-791.
[32]Behtn D, Herold C, Ohistein E, et al. Phannaeologieal charaeterization of SB-710411 Cpa- c[D-Cys-pal-D-Trp-Lys-val-cys]-Cpa-alnide,a novel PePtidie urotensin-ⅡrecePtor antagonist [J]. BrJPharmaeo, 2002,137(9):449-458.
[33]Camarda V, Guerrini R, Kostenis E, et al. A new ligand for the urotensinⅡreceptor [J]. Br J Phannaeo, 2002,137(7):311-314.
[34]Herold C, Behin D, Buekiey P, et al. The neuromedin B receptor antagonist,BIM-23127,is a Potent antagonist at human and rat urotensin-Ⅱreceptors [J]. Br J Phannaeol, 2003,39(6): 203- 207.
[35]Riccardo P, Paolo S, Sandro G, et al. Urantide:an ultrapotent urotensinⅡantagonist PePtide in the rat aorta [J]. Br J Pharmaco, 2003,40(23):1155-1158.
[36]Sidharta P, Wagner F, Bohnemeier H, et al. Phannacodynamics and phartnaco kineties ofthe urotensinⅡreceptor antagonist palosuran in macroalbuminuric diabetic Patienis [J]. Clin Phannacol Ther, 2006,80(1):246-256.
[37]Ross R. The pathogenesis of atherosclerosis, aperspective for the 1990s [J]. Nature, 1993,362 (29):801-809.
[38]梅美珍,徐也鲁,杨永宗(主编).动脉粥样硬化实验技术.中国病理生理学会动脉粥样硬化专业委员会, 1989,11:1-10.
[39]李才(主编).疾病模型与实验病理学.吉林大学出版社, 2002,82-83.
[40]杨小毅,万载阳,谭健苗,等.一种纯系小鼠动脉粥样硬化模型的建立[J].中国动脉硬化杂志, 1995,3(2):182-186.
[41]Groener J, Bax W, Stuani C, et al. Difference in substrate specificity between human and mouse lysosomal acid lipASe:low affinity for cholesteryl ester in mouse lysosomal acid lipASe [J]. Biochim Biophys Acta, 2000,1487(223):155-162.
[42]Tomkin G. Hyperglycaemia:the relation to dyslipidaemia and aterosclerosis [J]. Ir J Med Sci, 2002,171(3):161-164.
[43]张均田.现代药理实验方法.北京医科大学·中国协和医科大学出版社, 1998,1263-1271.
[44]Yang P, Rui Y, Li K, et al. Exp ression of intercellular adhension mo lecule-1 in U937 foam cells and the inh ibito ry effectof imperato rin [J]. Acta Pharmacol Sin, 2002,23(4):327- 330.
[45]杨鹏远,芮耀诚,张黎,等. U937泡沫细胞中血管内皮生长因子的表达及药物的抑制作用[J].药学学报, 2002,37(2):86-89.
[46]Yang P, Rui Y, Jin Y, et al. Antisense oligodeoxynucleo tide inh ibits vAScular endo thelial grow th facto r exp ression in U937 foam cells [J]. Acta Pharmacol Sin, 2003,24(6):610-614.
[47]Wissler R, Eilert M, Schroeder M, et al. Production of lipormatous and atheromatous arterial lesions in the albino rat [J]. Arch Pathol, 1954,57(9):333-341.
[48]成春英,何晓凡,孙勇,等.黄芎合剂对高脂血症大鼠动脉粥样硬化形成的影响[J].医学临床研究, 2006,23(4):468-470.
[49]王禄增,张梅英,季勇,等.脂蛋白a与动脉粥样硬化的研究进展[J].中国实验动物学报, 2002,10(2):113-115.
[50]Schmid K, M cshary W, Pameijer C, et al. Chemical and physiochemical studies on themineral deposits of the humanathero sclerosis aorta [J]. Atherosclerosis, 1980,37(3): 199-208.
[51]Fleckenstein-Grun G, Frey M, Luley C, et al. Differentiation calcium and choles teroldomin -ated types of atherosclerosis lesion:antiar-teriosclerotic Aspects of calcium antagonist [J]. Cardiov AS Pharm acol, 1991,18(16):1-9.
[52]焦宏,陈彦静.大鼠动脉粥样硬化模型的建立[J].河北北方学院学报, 2009,26(6):66-67.
[53]Weinstein D, Heider J. Antiatherogenic Properties of Calcium antagonists determinants [J]. Am J Cardiol, 1987,59(1):163-172.
[54]孙安阳,俞彰,钟慈声,等.大鼠动脉钙超负荷模型的建立及确证[J].中华医学杂志, 1999,79(10):769-772.
[55]Kramsch D. Atherosclerosis progression/regression:lipoprotein and vessel wall [J]. Atherscl- erosis, 1995,118(1):29-36.
[56]Price P, June H, Buckley J, et al. Osteop rotegerin inhibits artery Calcigfication induced bywarfarin and by vitamin D [J]. Arterioscler Thromb VASc Biol, 2001,21(17):1610-1616.
[57]吴开云,高摄渊,袁融,等.维生素D诱发大鼠动脉粥样硬化的实验研究[J].解剖学报, 1996,27(2):133-135.
[58]沈丽,卢维晟,姚俊宇,等.不同方法建立动脉粥样硬化大鼠模型的比较[J].心脏杂志, 2005, 17(1):18-20.
[59]杨鹏远,芮耀诚,焦亚斌,等.动脉粥样硬化大鼠实验模型的建立[J].第二大军医大学学报, 2003,24(7):802-804.
[60]温进坤,韩梅,杜玮南,等.一种快速建立大鼠动脉粥样硬化模型的实验方法[J].中国老年学杂志, 2001,21(1):50-51.
[61]郭延松,杨军珂.鼠动脉粥样硬化模型的建立[J].中国动脉粥样硬化杂志, 2003,11(1): 84-86.
[62]郭延松,吴宗贵,杨军珂,等.三种大鼠动脉粥样硬化模型复制方法的比较[J].中国动脉粥样硬化杂志, 2003,11(5):465-469.
[63]Sasaki S, Yoneda Y, Fujita H, et al. Asociation of blood pressure variability with induction of atherodclerosis in cholesterol-fed rats [J]. Am J Hypertens , 1994,7(5):453-459.
[64]张磊,陈国荣,郑荣远,等.高脂饲料加空气干燥术建立兔颈动脉粥样硬化模型[J].中国动脉硬化杂志, 2002,9(2):155-158.
[65]彭侃夫,孟建中,吴宗贵,等.苯那普利对家兔动脉粥样硬化形成和斑块破裂的作用[J].第二军医大学学报, 2003,24(7):798-801.
[66]Misra P, Sriv S, Singhal S, et al. Glutathione s-transferASe8-8 is localized in smooth muscle cells of rat aorta and induced in an experimental model of atherosclerosis [J]. Toxicol Appl Pharmacol, 1995,33(1):27-33.
[67]Span A, Grauls G, Bosman F, et al. Cytomegalovirus infection induces AS cular injury in the rat [J]. Atherosclerosis, 1992,93(122):41-52.
[68]Castellanos E, Sueishi K, Tanaka K, et al. Ultrastructural studies of rat arteriosclerosis induced by stimulation of the immune system with ovalbumin [J]. Acta Pathol J PN, 1991, 41(2): 113- 121.
[69]Mennander A, Tiisala S, Halttunen J, et al. Chronic rejection in rat aortic allografts.An exp- erimental model for transplant arteriosclerosis [J]. ArteriosclerThromb, 1991,11(4): 671-680.
[70]Cramer D, Chapman F, Wu G, et al. Cardiac transplantation in the rat,Alteration of the severity of donor graft arteriosclerosis by modulation of the host immune response [J]. Trans- plantation, 1990,50(3):554-558.
[71]李玉琳.分子病理学.人民卫生出版社, 2002,325-327.
[72]李建军,李庚山,黄从新,等.球囊损伤兔主动脉后核因子κB活性的动态变化[J].中国动脉硬化杂志, 2001,9 (1):34-36.
[73]卢次勇,凌文华,马静,等. ERK1/2在氧化型低密度脂蛋白诱导血管平滑肌细胞增殖中的作用[J].中国公共卫生, 2002,18(11):1286-1288.
[74]Lin G. Insights of high-density lipoprotein-mediated lipid ef-flux from cells [J]. Biochem Biophys ResCommun, 2002,291(4):727-73l.
[75]Shaul P. Endothelial nitric oxide synthase,caveolae and the development of atherosclerosis [J]. J Physio, 2003,547(1):21-33.
[76]山丽梅,张锦超,汪海,等.血管内皮细胞功能与动脉粥样硬化关系的研究进展[J].解放军药学学报, 2002,18(5):294-297.
[77]Furchgott R, Zawadzki J. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine [J]. Nature, 1980,288(5789):373-379.
[78]朱妙章,袁文俊,吴博威,等.心血管生理学与临床[J].高等教育出版社, 2004,152-153.
[79]温进坤,韩梅.血管平滑肌细胞[J].科学出版社, 2005,1-2.
[80]刘红梅,黄体钢.血管平滑肌细胞的培养及其在心血管疾病研究中的应用[J].实用心脑肺血管病杂志, 2005,13(6):364-368.
[81]王海燕,贾国良,张荣庆,等.人脐静脉内皮细胞共培养的人脐动脉平滑肌细胞生物学特性研究[J].中国临床康复, 2004,8(12):2258-2259.
[82]庄瑜,刘俊,肖明.血管平滑肌细胞在动脉粥样硬化中的作用[J].现代生物医学进展, 2009, 9(17):3375-3377.
[83]Schaub F, Han D, Liles W, et al. Fas/FADD mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells [J]. Nat Med, 2000, 6(7) 790- 796.
[84]Rensen S, Doevendans P, Van E, et al. Regulation and characteristics of Vascular smooth muscle cell phenotypic diversity [J]. Netherlands Heart J, 2007,15(3):100-108.
[85]王生兰,苏娟,徐一洲,等.大鼠血管平滑肌细胞体外培养的表型转换及其鉴定[J].中国动脉粥样硬化杂志, 2008,16(4):268-272.
[86]Libby P, Ridker P. Novel inflammatory markers of coronrisk:theory versusPraetiee [J]. Cireula- tion, 1999,100(1):148-1150.
[87]Albert C, Ma J, Fai N, et al. ProsPeetivestudy of C-reaetiveProtein,homoeyste Ine,andplas- matic levels as predietors of sudden cardiae death [J]. Cireulation, 2002,105(48):2595-2599.
[88]Libby P, Aikaw A. Stabilization of atheroselerotie plaques:new meehanisms and clinieal targets [J]. Nature Med, 2002,8(1):1257-1262.
[89]梁克山,谭兰. C反应蛋白与动脉粥样硬化性疾病[J].山东医学高等专科学校学报, 2006,28(2):135-139.
[90]Ridker P, Stampfer M, Rifai N, et al. Novel risk factors for systemic atherosclerosisa comp-areison of C-reactive protein, fibrinogen, homocysteine, lipoprotein,and standard cholesterol scrning predictors of peripheral arterial disease [J]. JA MA, 2001,285(12): 2481-2485.
[91]李志勇,李勋. C反应蛋白与冠状动脉粥样硬化性心脏病[J]. Medical Recap itulate, 2008, 14(23):3580-3585.
[92]Bang R, Marnell L, Mold C, et al. Analysis of binding sites in human C-reaetive Protein for Fe{gamma}RI,Fe{gamma}RllA,and Clq bysite-direete Mutagenesis [J]. J Biol Chem, 2005,280 (112):25095-25102.
[93]陈成,陈金水. C反应蛋白在动脉粥样硬化形成中的机制[J].中西医结合心脑血管病杂志, 2006,4(10):894-896.
[94]潘巍巍,江珊.超敏C反应蛋白与动脉粥样硬化的研究进展[J].中国心血管病研究, 2007,5(12):940-943.
[95]Lagrand W, Niessen H, Wblbink G, et al. C-reactive protein colocalizes with complement in human hearts during acute myoeardial infarction [J]. Cireulation, 1997,95(1):97-103.
[96]Li J, Fang C. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular disease [J]. Med Hypotheses, 2004,62(3):499-506.
[97]Reynolds G, Vance R. C-reactive protein immunohistochemical localization in nomal and atherosclerotic human aortas [J]. ArchPathol LabMed, 1987,111(2):265-269.
[98]Hatanaka K, Li X, Masuda K, et al. Immunohistochemical localization of C-reactive protein binding sites in human aortic lesions by a modified strep tavidin-biotin-staining method [J]. Pathol Int, 1995,45(6):635-641.
[99]Pasceri V, Willerson J, Yeh E, et al. Direct proinflammatory effect of C-reactive protein on human endothelial cells [J]. Circulation, 2000,102(8):2165-2168.
[100]Wang C, Li S, Weisel R, et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smoot h muscle [J]. Circulation, 2003,107(13):1783-1790.
[101]林杨,叶山东.单核细胞趋化蛋白-1与糖尿病动脉粥样硬化的关系.国际内科学杂志, 2007,34(7):381-385.
[102]徐梦丹,戴秋艳,孙宝贵.单核细胞趋化蛋白-1及受体在血管紧张素Ⅱ诱导的血管病变中的作用[J].心血管病学进展, 2006,27(4):505-508.
[103]王国平,邓仲端,瞿智玲.氧化修饰的低密度脂蛋白和极低密度脂蛋白对单核细胞MCP-1表达的影响[J].中华病理学杂志, 1996,25(4):220-223.
[104]王国平,邓仲端,瞿智玲.氧化修饰的极低密度脂蛋白对单核细胞趋化蛋白-1 mRNA表达的影响[J].中国病理生理杂志, 1997,13(2):114-117.
[105]王国平,邓仲端,瞿智玲.氧化修饰的低密度和极低密度脂蛋白对巨噬细胞单核趋化蛋白表达的影响[J].中华医学杂志, 1997,77(3):212-215.
[106]于光耀,邓仲端,瞿智玲.氧化修饰脂蛋白对内皮细胞单核细胞趋化蛋白-1表达的影响[J].中华病理学杂志, 1998,27(3):174-176.
[107]Frazier Jessen M, Kovacs E, et al. Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages [J]. J Immunol, 1995,154(4):1838- 1845.
[108]Klouche M, Gottschling S, Gerl V, et al.Atherogenic properties of enzy-matically degraded LDL:selective induction of MCP-1 and cytotoxic ef-fects on human macrophages [J]. Arterioscler Thromb Vasc Biol, 1998,18(9):1376-1385.
[109]Zeiher AM, Fisslthaler B, Schray B, et al. Nitric oxide modulates theexpressionof monocyte chemoattractant protein 1 in cultured human eothendilial cells [J]. CircRes, 1995, 76(6): 980-986.
[110]Weisberg S, Hunter D, Huber R, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding [J]. J Clin Invest, 2006,116(1):115-124.
[111]Viedt C, Vogel J, Athanasiou T, et al. Monocyte chemoattractant protein-1 induces prolife- ration and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-kappa B and activator protein-1 [J]. Arterioscler Thromb Vasc Biol, 2002,22 (6):914-920.
[112]陈志伟,李胜涛,陈琪,等.白细胞介素-6、白细胞介素-10与冠心病关系的研究进展[J].中西医结合心脑血管病杂志, 2008,6(8):949-951.
[113]Zhang P, Levy A, Ben-Simchon L, et al. Induction of neuronal and myelin-related gene expression by IL-6-receptor/IL-6:a study on embryonic dorsal root ganglia cells and isolated Schwann cells [J]. ExpNeurol, 2007,208(2):285-296.
[114]Soygur H, Palaoglu O, Akarsu E, et al. Interleukin-6 levels and HPA axis activation in breast cancer patients with major depressive disorder [J]. Prog Neuropsychopharmacol Biol Psychiatry,2007,31(6):1242-1247.
[115]Naya M, Tsukamoto T, Morita K, et al. Plasma interleukin-6 and tumor necrosis factor- alpha can predict coronary endothelial dysfunction in hypertensive pat inepts [J]. Hyperte- nsRes, 2007,30(6):541-548.
[116]Huber S, Sakkinen P, Conze D, et al. Interleukin-6 exacerbates early atherosclerosis in mice [J]. Arterioscler Thromb Vasc Biol, 1999,19(14):2364-2367.
[117]刘晓柳,李光千.白介素-6及其受体与心血管系统的研究进展[J].细胞分子与免疫学杂志, 2009,25(2):189-191
[118]张占彬.动脉粥样硬化中白细胞介素的研究进展[J]. Gan su Science and Technology, 2003,19(10):134-135.
[119]Wassmann S, Stumpf M, Strehlow K, et al. Interleukin-6 induces oxidative stress and endo- thelial dysfunction by overexpression of the angiotensinⅡtype1 receptor [J]. Circ Res, 2004,94(3):534-541.
[120]Baburhan G, Sibel G, Burhan T, et al. The roles of oxidized low-density lipoprotein and interleukin-6 levels in acute atheroma thrombotic and lacunar ischemic stroke [J].Angiology, 2008,59(1):224-229.
[121]刘娟,陈丽琴,陈丽琴,等.人冠状动脉粥样硬化斑块内白细胞介素6和18及肿瘤坏死因子-α表达与斑块稳定性有关[J].中国动脉硬化杂志, 2008,6(7):537-540.
[122]Tilg H, Trehu E, Atkins M, et al. Interleukin-6 as an anti-inflammatory cytokine:induction of circulating IL-1receptor antagonist and soluble tumor necrosis factor receptor p55 [J]. Blo- od, 1994,83(1):113-118.
[123]Liao H, Matsumoto A, Itakura H, et al. Transcriptional inhibition by interleukin-6 of the class a macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line [J]. Arterioscler Thromb Vasc Biol, 1999,19(13): 1872-1880.
[124]张恺芳,田英.转化生长因子β在动脉粥样硬化中的作用研究进展[J].中国动脉硬化杂志, 2006,14(7):636-638.
[125]胡艺琼,刘先哲.转化生长因子β对动脉粥样硬化中血管平滑肌细胞的作用及其影响[J].时珍国医国药, 2008,19(1):167-169.
[126]郑琼莉,祝炜,贾晶,等.转化生长因子β1与心血管疾病[J].中国心血管病研究杂志, 2006,4(7):550-551.
[127]梅卫义,杜志民,陈国伟.转化生长因子-β与冠心病[J].国外内科学分册, 2005,32(2): 70-74.
[128]Massague J, Chen Y. Controlling TGF-βsignalling [J]. Gene Dev, 2000,14(3):627-632.
[129]Blobe G, William P. chiemann,Harvey FLodish,Role of transforming growth factorβin human disease [J]. N Engl J Med, 2000,342(275):1350-1357.
[130]金炜,董维平,杨红,等.转化生长因子β1在动脉粥样硬化形成中的作用及机制研究[J].中国药理学通报, 2003,19(6):650-653.
[131]Grainger D, Mosedale D, Metcalfe J, et al. Dietary fat and reduced levels of TGF beta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions [J]. J Cell Sci, 2000,113(8):2355-2361.
[132]DingA, Nathan C, Graycar J, et al. Macrophage deactivating factor and trans-forming growth factors-β1-β2 and-β3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-γ[J]. J Immunol, 1990,145(11):1940-1944.
[133]Lutgens E, Gijbels M, Smook M, et al. Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression [J]. Arteriosclerosis Thromb Vasc Biol, 2002,22(5):975-982.
[134]Camarda V, Rizzi A, Calo G, et al. Effects of human urotensinⅡin isolated vessels of various species:comparison with other vasoactive agents [J]. Naunyn Schmiedebergs Arch Pharmacol, 2002,365(1):141-149.
[135]Rossowski W, Cheng B, Taylor J, et al. Human urotensinⅡinduced aorta ring contractions are mediated by protein kinase C,tyrosine kinases and Rho-kinase:inhibition by somatos tatin receptor antagonists [J]. Eur JPharmacol, 2002,435(3):159-170.
[136]Bottrill F, Douglas S, Hiler C, et al. Human urotensinⅡis an endothelium -dependent vasodilator in rat small arteries [J]. Br J Pharmacol, 2001,130(8):1865-1870.
[137]Ishihata A, Sakai M, Katano Y, et al. Vascular contractile effect of urotensinⅡin young and aged rats:influence of aging and contribution of endothelial nitric oxide [J]. Peptides, 2006, 27(1):80-86.
[138]张丽芳,陈莉,丁文惠,等.血浆尾加压素Ⅱ浓度与冠状动脉病变程度的关系[J].中日友好医院学报, 2008,22(1):3-5.
[139]李康,丁文惠,史力斌,等.尾加压素Ⅱ对大鼠胸主动脉球囊损伤后血管重塑的作用[J].中国病理生理杂志, 2008,24(4):674-679.
[140]Bousette N, Patel L, Douglas S, et al. Increased expression of urotensinⅡand its cognate recep tor GPR14 in atherosclerotic lesions of the human aorta [J]. Atherosclerosis, 2004,176 (6):117-123.
[141]Vincent S, Erik L, Jacques B, et al. Human urotensinⅡinduced contraction and arterial smooth muscle cell proliferation are mediated by rhoA and rhokinase [J]. Circulation Res, 2001, 88(45):1102-1104.
[142]唐朝枢,刘秀华.细胞外信号引起核反应的细胞信号转导途径[J].药理学进展, 1998 (1):72-85.
[143]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):155-157.
[144]彭旭,尹航,汪丽蕙,等.尾加压素Ⅱ增加血管平滑肌细胞粘着斑激酶的含量和活力[J].生理学报, 2000,52(6):455-458.
[145]齐永芬,卜定方,牛大地,等.尾加压素Ⅱ促进大鼠血管平滑肌细胞内皮素生成[J].科学通报, 2002,47(4):289-292.
[146]任安经,林丽,袁文俊.尾加压素Ⅱ—促细胞增殖的活性肽[J].心脏杂志, 2004,16 (6):572- 574.
[147]Watanabe T, Takahashi K, Kanome T, et al. Human urotensinⅡpotentiates the mitogenic effect ofmildly oxidized low density lipo protein on vascular smooth muscle cells:com- parison,with other vasoactive agents and hydrogen peroxide [J]. Hypertens Res, 2006, 29(4): 821-831.
[148]Wang Y, Ding Y, Zhu Y, et al. Role of PKC in the novel synergistic action of urotensinⅡand angitensinⅡand in urotensinⅡinduced vasoconstriction [J]. Am J Physiol Heart Circ Physiol, 2007,292(2):348-359.
[149]Camarda V, Song W, Marzola, et al. Urantide mimies urotensin-Ⅱinducede ale-ium release in cells expressing reeombinant UT reeePtors [J]. EurJ Phannaeo, 2004,498(1):83-86.
[150]Dhanak D, Kllight S, et al. Sulfonamide derivative urotensinⅡreceptor anta-gonists, preparation,Pharlnaceutieal compositions,and therapeutie use [J]. PCT Int APP, 2001, 598 (2): 283-286.
[151]Valeria C, Martina S, Wei S, et al. In vitro and in vivo pharmacological Chara-cterizationof the novel UT receptor ligand[Pen5,DTrp7,Dab8]urotensin (4–11)(UFP-803) [J]. British Journal of Pharmacology, 2006,147(1):92-100.
[152]Johns D, Gao Z, Naselsky D, et al. UrotensinⅡImediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators [J]. Naunyn Schmiedebergs Arch Pharmacol, 2004,370(4):238-250.
[153]姚华,陈志武. Urantide对实验性心肌缺血及缺氧再给氧损伤的影响[J].安徽医科大学学报, 2008,3(2):294-296.
[154]赵娟,任立群. VD3联合高脂饲料建立大鼠动脉粥样硬化模型[J].实用医学杂志, 2009,25 (21):3569-3571.
[155]Shi L, Ding W, Li D, et al. Proliferation and anti-apop totic effects of human urotensinⅡon human endothelial cells [J]. Atherosclerosis, 2006,188(2):260-264.
[156]Sauzeau V, LeMellionnec E, Bertoglio J, et al. Human urotensinⅡinduced contraction and arterial smooth muscle cell proliferationare mediated by RhoA and Rho-Kinase [J]. Circ Res, 2001,88(67):1102-1104.
[157]Matsusaka S, Wakabayashi I. Enhancement of vascular smooth muscle cellmigration by urotensinⅡ[J]. Naunyn Schmiedebergs Arch Pharmacol, 2006,373(2):381-386.
[158]Claesson Welsh L. Signal transduction by vascular endothelial growth factor receptors [J]. Biochem Soc Trans, 2003,31(1):20-24.
[159]司徒振强,吴军正.细胞培养.世界图书出版公司, 2004,245.
[160]Bousette N, Patel L, Douglas S, et al. Increased exp ression of urotensinⅡand its cognate reeptor GPR14 in atherosclerotic lesions of the human aorta [J]. Atherosclerosis, 2004,176 (1): 117-123.
[161]李立.维持血液透析患者微炎症状态与血管通路功能丧失的相关性研究[J].东南大学硕士, 2006,34.
[162]Penn M, Topoi E. Tissue factor,the emerging link between inflammation,thrombosis and vascular remodeling [J]. Cir Res, 2001,89(1):1-2.
[163]Yaso JimaK, Sehwab C, Ger E, et al. Generation of C-reactive protein and complement components in atherosclerotic plaques [J]. Am J Pathol, 2001,158(34):1039-1051.
[164]Tomai F, Crea F, Gaspardone A, et al. Unstable angina and Elevated C-reactive protein levels predict enhanced vasoreactivity of the eu1prit lesion [J]. Cireulation, 2001,104(74): 1471-1476.
[165]Paseeri V, Willersn T, Yeh T, et al. Direet proinflammatory effect of C-reaetive Protein on human endothelial cells [J]. Circulation, 2000,102(234):2165-2168.
[166]Fiehtlseherer S, Rosenberger G, Walter H, et al. Elevated C-reactive protein Levels and impaired endothelial vasoreactivity in patients with coronary artery Disease [J]. Cireulation, 2000,102(43):1000-1043.
[167]Boos J, Lip G. .Elevated high-sensitive C-reactive Protein,large arterial Stiffness and atherosclerosis:arelationship between inflammation and hypertension.Journal of Human [J].Hypertension, 2005,19(5):511-516.
[168]Bisoendial J, Kastelein J, Levels H, et al. Aetivation of inflammation and Coagulation after infusion of C-reactive protein in humans [J]. Cire Res,2005,96(6):714-716.
[169]Yu X, Dluz S, Graves T, et al.Elevated expression of monocyte chemoattractant Protein-1 by vascular smooth muscle cells in hypercholesterolemic p rimates [J]. Proc Natl Acad Sci USA, 1992,89:6953-6957.
[170]Weber C, Schober A, Zernecke A, et al. Chemokines key regulators of mononuclear cell recruitment in atherosclerotic vascular disease [J]. Arterioscler Thromb Vasc Biol,2004,24 (9): 1997-2008.
[171]Rus G, Vlaicu R, Niculescu F, et al. Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall [J]. Atherosclerosis, 1996,127(2):263-271.
[172]潘晓宏,单江,罗建红,等.碱性成纤维细胞生长因子和白细胞介素-6促进大鼠血管平滑肌细胞增殖的协同作用[J].中国动脉硬化杂志, 2000,8(3):233-235.
[173]Kranzhofer R, Clinton S, Ishii K, et al. Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes [J]. Circ Res, 1996, 79(2):286-294.
[174]Piek E, Heldin C, Dij P, et al. Specificity,diversity,and regulation in TGF-βsuperfamily signaling [J]. FASEB J, 1999,13(436):2015-2212.
[175]Argmann C, Diepstraten C, Sawyez C, et al. Transforming growth factor-beta1 inhibitsmacrophage cholcsteryl ester accumulation induced by native and oxidized VLDL rem- nants [J]. Arterioscler Throm Vasc Bio, 2001,21(12):2011-2018.
[176]赵贞,吴金玉.Ⅳ型胶原在糖尿病肾病中的作用[J].深圳中西医结合杂志, 2009,19(2): 121-123.
[177]杨方,赵培真.胶原与动脉粥样硬化[J].中国动脉硬化杂志, 1996,4(3):226-229.
[178]Tanimura A, MeGregor D, Amderson H, et al. Calcification in atherosclerosis:Human studies [J]. J Exp Pathol, 1986,5(1):261-273.