卡托普利对缺氧诱导的肺动脉平滑肌细胞增殖和胶原合成的抑制作用(英文)

目的:观察卡托普利(Cap)抑制缺氧诱导的肺动脉平滑肌细胞(VSMC)增殖和胶原合成的作用,方法:采用细胞计数,[~3H]脱氧胸苷,[~3H]脯氨酸掺入和细胞内游离钙测定的方法。结果:卡托普利(Cap,1μmol·L~(-1))抑制缺氧诱导的VSMC中细胞数目,[~3H]脱氧胸苷和[~3H]脯氨酸掺入及细胞内游离钙的增高,较缺氧组分别降低了25％,36％,21％和16％,硝苯吡啶也具有上述抑制作用,Bay-K-8644促进VSMC中细胞数目,[~3H]脱氧胸苷和[~3H]脯氨酸掺入及细胞内游离钙的增高,分别增加35％,55％,36％,34％,这种作用可被Cap阻断。结论:Cap抑制缺氧诱导的肺动脉平滑肌细胞增殖和胶原合成,这可能与阻断L型钙通道有关。     

卡托普利对主动脉平滑肌细胞增殖的影响

目的：观察卡托普利（Ｃａｐ）对平滑肌细胞（ＳＭＣ）增殖的作用及其作用机制。 方法：用高脂血清（ＨＬＳ）造成体外培养猪主动脉ＳＭＣ增殖。 结果：ＨＬＳ培养促进ＳＭＣ增殖，加Ｃａｐ（０．２ｍｇ·Ｌ＾－１）后拮抗ＳＭＣ增殖，使丙二醇（ＭＤＡ）含量，纤溶酶原激活物抑制物（ＰＡＩ）活性明显减少，６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）及环腺苷－磷酸（ｃＡＭＰ）含量明显增加（Ｐ〈０．０５－０．０１）     

卡托普利对自发性高血压大鼠血管平滑肌细胞增殖及癌基因和 …

目的：观察卡托普利（Ｃａｐ）的自发性高血压大鼠（ＳＨＲ）血管平滑肌细胞（ＶＳＭＣ）增殖的作用及对原癌基因及抑癌基因的影响。方法：氚－胸腺嘧啶核苷（＾３Ｈ－ＴｄＲ）参入，电镜，原位杂交及Ｎｏｒｔｈｅｒｎ ｂｌｏｔ杂交。结果：Ｃａｐ在降低ＳＨＲ血压同时，能减少ＶＳＭＣ的线粒体，粗面内质网及＾３Ｈ－Ｔｄ参入量（Ｐ〈０．０１），并有逆转ｃ－ｆｏｓ，ｃ－ｍｙｃ，ｃ－ｓｉｓ原癌基因ｍＲＮＡ表达增强（Ｐ〈０．０     

肾上腺髓质对缺氧所引起的肺动脉血管平滑肌细胞增殖的影响

研究肾步腺髓质(AM)对缺氧所引起的肺动脉血管平滑肌细胞(PASMC)增殖的影响及其机制。方法：体外培养大鼠PASMC,观察不同缺氧培养时间细胞上清液AM浓度的变化;以H-TdR渗入法,观察缺氧条件下无血清和含血清培养的PASMC的增殖情况,以及不同浓度的AM对细胞增殖的影响。结果：缺氧培养24h起细胞上清液AM浓度明显升高;缺氧使含血清培养的PASMC增殖增加;10^-7mol／L以上浓度的AM抑制含血清培养的PASMC的增殖。结论：结果提示PASMC可能需丰外源性生长因子作用的基础上直接感受缺氧发生增生反应;AM能抑制缺氧所引起的PASMC的增殖,因此可能对缺氧性血管构型竽建具有一定意义。     

卡托普利和依那普利对血管平滑肌细胞内钙的影响

检测ＡＣＥ抑制剂对主动脉平滑肌细胞内Ｃａ＾２＋的影响。用荧光标计和图象处理技术。ＳＨＲ细胞内Ｃａ＾２＋以及ＫＣｌ，ＮＥ和Ａｎｇ在ＳＨＲ细胞引起的Ｃａ＾２＋增加多于ＷＫＹ细胞。Ｃａｐ和Ｅｎａ不影响ＫＣｌ     

卡托普利对自发性高血压大鼠血管平滑肌细胞增殖及癌基因和抑癌基因的影响

目的：观察卡托普利（CaP）对自发性高血压大鼠（SHR）血管平滑肌细胞（VSMC）增殖的作用及对原癌基因及抑癌基因的影响。方法：氚-胸腺嘧啶核苷（3H－TdR）参入，电镜，原位来交及Northernblot杂交。结果：CaP在降低SHR血压同时，能减少VSMC的线粒体，粗面内质网及3H－TdR参入量（P<0.01），并能逆转c－fos，c－myc，c－sis原癌基因mRNA表达增强（P<0.05或0.01），p53抑癌基因mRNA表达减弱（P＜0．01）。结论：Cap能抑制SHR的VSMC增殖，与癌基因调控的分子生物学机制有关。     

硝苯地平对大鼠肺动脉平滑肌细胞增殖的影响

目的研究钙拮抗剂硝苯地平对肺动脉平滑肌细胞增殖的影响 ;探讨钙离子拮抗剂对肺血管构型重建的抑制作用。方法分离培养大鼠肺动脉平滑肌细胞 ;用MTT法检测细胞增殖 ;用流式细胞仪分析细胞周期。结果硝苯地平能剂量依赖地抑制血清诱导的肺动脉平滑肌细胞增殖 ,对照组的增殖指数和S期细胞分数为 36 0 2 %和 15 88% ;硝苯地平 1× 10 -8mol·L-1、1× 10 -7mol·L-1、1× 10 -6mol·L-1组的PI和SPF分别为 31 16 %、2 6 94 %、2 4 95 %和 13 10 %、11 4 7%、9 6 0 %。结论肺动脉平滑肌细胞增殖中有钙离子信号的参与 ;硝苯地平能够抑制血清诱导的肺动脉平滑肌细胞增殖 ;硝苯地平对肺血管构型重建可能有一定的抑制作用     

灯盏花素对原代培养的牛肺动脉平滑肌细胞增殖的抑制作用

目的　研究灯盏花素对肺动脉平滑肌细胞增殖的影响。方法　用原代培养的小牛肺动脉平滑肌细胞 ,采用MTT比色法、3 H TdR参入法、流式细胞术、Giemsa染色对肺动脉平滑肌细胞增殖的影响进行观察。结果　与对照组相比 ,灯盏花素处理组可抑制肺动脉平滑肌细胞的增殖 ,而且主要是细胞周期的G0 /G1到S期受机制。结论　灯盏花素可显著地抑制肺动脉平滑肌细胞的增殖 ,其机制可能是其对蛋白激酶C的抑制作用     

Inhibitory effects of lithospermic acid on proliferation and migration of rat vascular smooth muscle cells

Aim： To understand the effects of lithospermic acid （LA）, a potent antioxidant from the water-soluble extract of Salvia miltiorrhiza, on the migration and proliferation of rat thoracic aorta vascular smooth muscle cells （VSMCs）. Methods： VSMC migration, proliferation, DNA synthesis and cell cycle progression were investigated by transwell migration analysis, 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, bromodeoxyuridine （BrdU） incorporation assay, and flow cytometric detection, respectively. Intracellular reactive oxygen species （ROS） generation was detected using 2＇,7＇-dichlorofluorescin diacetate （DCFH-DA）. The expression of cyclin D1 protein and matrix metalloproteinase-9 （MMP-9） protein, as well as the phosphorylation state of ERK1/2, were determined using Western blots. The activity of MMP-9 and the expression of MMP-9 mRNA were assessed by gelatin zymography analysis and RT-PCR, respectively. Results： LA （25-100 pmol/L） inhibited both lipopolysaccharide （LPS）- and fetal bovine serum （FBS）-induced ROS generation and ERK1/2 phosphorylation. By down-regulating the expression of cyclin D1 and arresting cell cycle progression at the G1 phase, LA inhibited both VSMC proliferation and DNA synthesis as induced by 5% FBS. Furthermore, LA attenuated LPS-induced VSMC migration by inhibiting MMP-9 expression and its enzymatic activity. Conclusion： LA is able to inhibit FBS-induced VSMC proliferation and LPS-induced VSMC migration, which suggests that LA may have therapeutic effects in the prevention of atherosclerosis, restenosis and neointimal hyperplasia.     

卡托普利对主动脉平滑肌细胞增殖的影响

卡托普利对主动脉平滑肌细胞增殖的影响熊一力１，赵华月（同济医科大学同济医院内科，武汉４３００３０，中国）关键词卡托普利；胸主动脉；血管平滑肌；培养的细胞；高脂血清；胸苷；６酮前列腺素Ｆ１α；环腺苷一磷酸；丙二醛；血纤维蛋白溶酶原失活剂目的：观察卡托...     

Inhibitory effect of pentalenolactone on vascular smooth muscle cell proliferation

The effect of pentalenolactone, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, on rat vascular smooth muscle cell proliferation was studied. Addition of pentalenolactone together with serum to quiescent cells dose-dependently inhibited cell proliferation and DNA synthesis. This inhibition was not associated with cell death. When quiescent cells were stimulated with serum and then treated with pentalenolactone, the inhibitory effect on the DNA synthesis declined gradually. A similar result was obtained when PD 98059 (2'-amino-3'-methoxyflavone), an inhibitor of extracellular signal-regulated kinase1/2 (ERK1/2) kinase (MEK1/2), was added to the cells after serum stimulation. Pentalenolactone inhibited serum or protein kinase C activator (phorbol 12,13-dibutyrate)-induced phosphorylation of ERK1/2 and MEK1/2. In contrast, pentalenolactone had little effect on platelet-derived growth factor receptor autophosphorylation. Taken together, these results indicate that pentalenolactone inhibits vascular smooth muscle cell proliferation, and that this inhibition appears to be mediated by inhibition of the ERK1/2 cascade.     

川芎嗪对家兔主动脉损伤平滑肌细胞增殖的抑制作用

AIM: To study the inhibitory effect of ligustrazine (Lig) on growth of cultured rabbit aortic vascular smooth muscle cells (VSMC) after balloon injury. METHODS: Twenty New Zealand white rabbits were subjected to arterial injury with a balloon catheter (810 kPa for three consecutive inflations, 1 min each time). The uptake of [3H]thymidine in primary cultural VSMC incubated with rabbit serum, which obtained from the animals treated without or with Lig (40 mg.kg-1.d-1, i.v.) for 21 d (7 d before and 14 d after the injury procedure) was determined. The determination was performed in direct addition of TMP to culture as well. And histological cross-sections of the blood wall were also analyzed. RESULTS: After balloon injury the intimal thickening (77 +/- 23) microns and lumen diameter narrowing (877 +/- 118) microns in dilated sites were increased significantly than the normal adjacent wall [(41 +/- 13) microns, P < 0.01; (1033 +/- 175) microns, P < 0.05, respectively]. Treatment with Lig decreased both intimal thickening (56 +/- 16) microns (P < 0.05) and lumen diameter narrowing (1023 +/- 157) microns (P < 0.05). Lig inhibited [3H]thymidine uptake in VSMC incubated with the serum obtained from these rabbits. Direct addition of Lig inhibited [3H]thymidine uptake in cultured VSMC in a dose-dependent manner (40-4000) micrograms/well. CONCLUSION: Lig shows a pronounced inhibitory effect on VSMC proliferation after balloon injury.     

ACE2通过下调AT1R和ERK1/2的磷酸化

目的探讨血管紧张素转换酶2(ACE2)对血管紧张素Ⅱ1型受体(AT1R)和细胞外基质激酶(ERK)1/2磷酸化水平及细胞增殖的影响。方法荧光显微镜下观察绿色荧光蛋白(GFP)的表达;将载有ACE2基因慢病毒表达载体(Lentiviral-ACE2)以感染复数为10(MOI=10)感染平滑肌细胞不同时间(24、48、72、96 h);采用CCK-8法检测平滑肌细胞增殖;Western blot检测ACE2、AT1R及ERK1/2磷酸化水平。结果目的蛋白GFP表达量明显增加,慢病毒ACE2的表达量成时间依赖性增加,并且在96 h时蛋白表达量较对照组和空载体组明显升高,(1.22±0.06 vs 0.53±0.03和0.53±0.09,P<0.05,n=4);AngⅡ(10-7 mol·L-1)可以促进平滑肌细胞的增殖,ACE2能够抑制AngⅡ诱导的平滑肌细胞增殖(0.53±0.10 vs 0.68±0.03,P<0.05,n=5);AngⅡ(10-7mol·L-1)作用平滑肌细胞12 h后AT1R明显上调,同时ACE2明显抑制AngⅡ诱导的AT1R的上调(0.34±0.01 vs 0.73±0.07,P<0.05,n=4);ACE2能够明显抑制AngⅡ诱导的ERK1/2的磷酸化水平(0.43±0.06 vs 0.71±0.08,P<0.05,n=4)。结论 ACE2可以通过下调AT1R和/及ERK1/2的磷酸化水平而抑制平滑肌增殖,提示ACE2的过表达具有血管保护作用。     

ACE2通过下调AT1R和ERK1/2的磷酸化而抑制平滑肌细胞的增殖

目的 探讨血管紧张素转换酶2(ACE2)对血管紧张素Ⅱ1型受体(AT1R)和细胞外基质激酶(ERK)1/2磷酸化水平及细胞增殖的影响.方法 荧光显微镜下观察绿色荧光蛋白(GFP)的表达;将载有ACE2基因慢病毒表达载体(Lentiviral-ACE2)以感染复数为10(MOI=10)感染平滑肌细胞不同时间(24、48、72、96 h);采用CCK-8法检测平滑肌细胞增殖;Western blot检测ACE2、AT1R及ERK1/2磷酸化水平.结果 目的 蛋白GFP表达量明显增加,慢病毒ACE2的表达量成时间依赖性增加,并且在96 h时蛋白表达量较对照组和空载体组明显升高,(1.22±0.06 vs 0.53±0.03和0.53±0.09,P<0.05,n=4);AngⅡ(10-7 mol·L-1)可以促进平滑肌细胞的增殖,ACE2能够抑制AngⅡ诱导的平滑肌细胞增殖(0.53±0.10 vs 0.68±0.03,P<0.05,n=5);AngⅡ(10-7 mol·L-1)作用平滑肌细胞12 h后AT1R明显上调,同时ACE2明显抑制AngⅡ诱导的AT1R的上调(0.34±0.01 vs 0.73±0.07,P<0.05,n=4); ACE2能够明显抑制AngⅡ诱导的ERK1/2的磷酸化水平 (0.43±0.06 vs 0.71±0.08,P<0.05,n=4).结论 ACE2可以通过下调AT1R和/及ERK1/2 的磷酸化水平而抑制平滑肌增殖,提示ACE2的过表达具有血管保护作用.     

藳本内酯和丁烯酜内酯对bFGF诱导的大鼠平滑肌细胞异常增殖的抑制作用

目的研究藳本内酯和丁烯酜内酯与大鼠主动脉平滑肌细胞的亲合活性，及其对主动脉平滑肌细胞增殖的抑制作用。方法采用大鼠主动脉细胞膜色谱模型观察藳本内酯和丁烯酜内酯的保留特性；培养并分离纯化大鼠主动脉平滑肌细胞，采用bFGF诱导平滑肌细胞增殖，以MTT比色法检测藳本内酯和丁烯酜内酯对平滑肌细胞增殖的抑制作用。结果藳本内酯和丁烯酜内酯与大鼠主动脉平滑肌细胞膜有亲和性，其保留行为与钙离子受体拮抗剂维拉帕米相似；藳本内酯和丁烯酜内酯不会引起正常大鼠主动脉平滑肌细胞增殖，但能明显抑制bFGF诱导的大鼠主动脉平滑肌细胞的增殖。其有效浓度分别为5.5和11.1 μmol·L^-1(P<0.05)。结论藳本内酯和丁烯酜内酯与大鼠主动脉平滑肌细胞具有亲和力，能抑制血管平滑肌细胞的异常增殖。     

卡托普利对血管平滑肌细胞内pH影响

卡托普利对血管平滑肌细胞内ｐＨ影响１齐建华，章鲁２，王军，顾培坤，金正均，黄明智３（上海第二医科大学药理教研室，２计算机医学应用教研室，３上海市高血压研究所，上海２０００２５，中国）王新明（中国科学院上海细胞生物学研究所，上海２０００３１，中国）关键...     

Ligustilide inhibits vascular smooth muscle cells proliferation

Proliferation and migration of vascular smooth muscle cells (VSMCs) are believed to develop atherosclerosis and venous bypass graft disease. Ligustilide is widely used to treat some pathological settings such as atherosclerosis and hypertension. The aim of this study was to examine the effect of ligustilide on VSMCs proliferation. The results show that ligustilide significantly inhibited VSMCs proliferation and cell cycle progression. Further analysis shows that ligustilide suppressed reactive oxygen species production and extracellular signal-related kinases (ERK), c-Jun N-terminal protein kinase (JNK), and p38 MAP kinase. Cells were treated with antioxidant, superoxide dismutase, catalase, and DPI, respectively, leading to repress ERK, JNK, and p38 activation. The inhibitors of mitogen activated protein kinase (MAPK), PD98059, SB203580, and Sp600125, inhibited cell proliferation. These findings suggest the antiproliferative effect of ligustilide was associated with the decrement of reactive oxygen species resulting in the suppression of MAPK pathway. Thus, ligustilide contribute to be the effective agent in preventing cardiovascular diseases.