Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles

Ginkgo biloba extract (GBE) is composed mostly of two constituents: One is terpenoids (such as bilobalide, ginkgolides A, B and C), and the other is flavonoids (such as quercetin and rutin). After oral administration of GBE (160 mg) to healthy volunteers, the plasma concentrations of ginkgolides A and B and bilobalide are 41.8, 5.6 and 37.6 ng/ml, respectively. GBE and bilobalide cause a potent concentration-dependent relaxation. NG-Monomethyl-l-arginine acetate (l-NMMA), an NO synthesis inhibitor, reduces the vasodilation induced by GBE. Furthermore, the vasorelaxation of GBE is attenuated in Ca2+-free medium. Bilobalide possesses similar mechanisms. The other constituents also produce vasorelaxation. On the other hand, all the compounds markedly modify the action potential configuration in guinea pig ventricular cardiomyocytes. GBE prolongs the action potential duration (APD), whereas bilobalide shortens the APD. In patch-clamp experiments, GBE markedly inhibits the Ca2+ current (ICa), the delayed rectifier K+ current (IK) and the inwardly rectifying K+ current (IK1). On the contrary bilobalide enhances the ICa and IK currents concentration-dependently. The other constituents do not cause their actions in a uniform direction. In the rat sino-atrial (SA) node, GBE causes a negative chronotropic effect. These results indicate that GBE and the constituents produce effective electropharmacological actions in the cardiomyocytes and cause vasodilation, mainly due to the inhibitions of Ca2+ influx through the Ca2+ channel and the activation of NO release in the endothelium and aortic vascular muscles.     

gax基因与血管平滑肌细胞增殖

gax基因是一个主要存在于心血管系统的同源盒基因,能显著抑制血管平滑肌细胞增殖,有望成为防治动脉粥样硬化和经皮血管介入治疗后再狭窄的靶基因。     

tMfn2基因抑制血管平滑肌细胞增殖的作用与机制

目的 比较线粒体融合素基因2(Mfn2)和去除穿膜区序列的大鼠线粒体融合素基因2(tMfn2)对大鼠血管平滑肌细胞(VSMCs)增殖的作用,探讨tMfn2基因对VSMCs增殖的影响及其相关的信号通路.方法 用携带tMfn2基因和Mfn2基因的重组腺病毒(Adv-tMfn2和Adv-Mfn2)感染VSMCs,检测tMfn2蛋白和Mfn2蛋白在细胞中的表达水平;细胞计数法、四甲基偶氮唑盐(MTT)法检测VSMCs的增殖;流式细胞术检测tMfn2基因对VSMCs周期的影响;Western blot分析各组磷酸化ERK1/2和磷酸化Raf-1蛋白表达水平的变化;采用方差分析对数据进行统计学处理.结果 Adv-tMfn2和Adv-Mfn2感染VSMCs后能有效表达出相应蛋白;细胞计数和MTT结果显示,tMfn2和Mfn2均使VSMCs增殖受到明显抑制(P<0.01),且前者较后者抑制效果更明显(P<0.01);流式细胞术结果表明tMfn2和Mfn2使多数VSMCs停滞于G0/G1期,细胞比例为(88.01±4.38)%和(67.43±6.21)%,可见tMfn2基因对细胞剧期的影响更明显(P<0.01).进一步研究表明tMfn2比Mfn2更能降低磷酸化ERK1/2(p-ERK1/2)和磷酸化Raf-1(p-Raf-1)的表达水平(P<0.01).结论 与Mfn2基因相比,tMfn2基因更能显著抑制VSMCs增殖,使细胞周期停滞于G0/G1期.这一作用主要通过抑制Ras-Raf-ERK1/2信号通路,下调磷酸化Raf-1蛋白表达,进而抑制ERK1/2的磷酸化而实现.     

Inhibition of serotonin-induced vascular smooth muscle cell proliferation by sarpogrelate.

Antiproliferative behavior of sarpogrelate (Anplag, MCI-9042, (+/-)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-pro pyl hydrogen succinate hydrochloride), a serotonin 2A (5-HT2A) receptor antagonist, was established using radioactive incorporation of [(3)H]thymidine, [(3)H]uridine, and [(3)H]phenylalanine in cultured rat aortic smooth muscle cells in response to a 5-HT-induced cytokine trigger. Fluorescence-activated cell sorting was used to confirm these observations. 5-HT-induced DNA, RNA, and protein synthesis were inhibited maximally at a concentration of 1 microM sarpogrelate. Although other cytokines such as platelet-derived growth factor and endothelin also induced DNA, RNA, and protein synthesis in rat aortic smooth muscle cells, cell proliferation was not influenced by sarpogrelate, even at large pharmacological concentrations (10 microM). Sarpogrelate's antiproliferative actions were found to be more potent than ketanserin. These data indicate that sarpogrelate operates as a specific inhibitor of 5-HT-mediated cell proliferation and is a good candidate for preventing serotonin-induced neointimal hyperplasia.     

Role of cholesterol-accumulating macrophages on vascular smooth muscle cell proliferation.

The proliferation of vascular smooth muscle cells (VSMC) was stimulated by co-incubation with macrophages. Further stimulation was observed when co-incubated macrophages were supplied with LDL or cholesterol. However, the stimulation of VSMC proliferation did not result from co-incubation with macrophages supplemented with acetylated LDL or delipidated LDL. The addition of anti-PDGF antibody partially abolished the stimulation of VSMC proliferation induced by co-incubation with macrophages supplemented with LDL or cholesterol. A high concentration of prostaglandin E2 inhibited the proliferation of VSMC stimulated by PDGF and plasma-derived serum when they were at the G0/G1 stage. However, the inhibitory effect of prostaglandin E2 on proliferation was not observed when cells were incubated with macrophages supplemented with LDL or cholesterol in spite of the promotion under these conditions of prostaglandin E2 production. These results suggest that cholesterol-accumulating macrophages may exert a regulatory effect on the proliferation of VSMC through the synthesis and secretion of platelet-derived growth factor (PDGF) and prostaglandin E2, besides foam-cell formation.     

雷公藤内酯醇抑制血管平滑肌细胞增殖的研究

目的:探讨雷公藤内酯醇对血清诱导的大鼠血管平滑肌细胞(VSMC)增生的影响及其作用机制。方法:体外培养大鼠胸主动脉平滑肌细胞,用细胞计数法观察雷公藤内酯醇对细胞增生的抑制作用,采用流式细胞仪进行细胞周期分析,逆转录-聚合酶链反应(RT-PCR)法检测细胞c-fos的mRNA表达水平。结果:雷公藤内酯醇明显抑制血清诱导的大鼠VSMC增生;阻断细胞周期中细胞由G0/G1期向S期转化;RT-PCR检测显示雷公藤内酯醇能明显抑制原癌基因c-fos的表达,其作用呈剂量依赖性。结论:雷公藤内酯醇可抑制血清诱导的大鼠VSMC增生,下调原癌基因c-fos的表达。     

Age-related changes in relaxant response of vascular smooth muscles to atrial natriuretic peptide

The effect of aging on responses of vascular smooth muscles to atrial natriuretic peptide (ANP) and other vasodilator substances was investigated in isolated rat aortae, rat renal arteries and monkey renal arteries which were precontracted with norepinephrine. There was no significant difference in the ANP-induced maximum relaxation between young and old rat aortae. However, the concentration of agonists causing a 50% relaxation (ED50) value for the old rats was 7.3 times greater than that for the young ones. In rat and monkey renal arteries, the ED50 ratios were 6.2 and 3.8, respectively. The relaxant responses of the rat aortae to isoproterenol and acetylcholine also decreased with increasing age. The ED50 ratios for isoproterenol and acetylcholine were more than 40 and 17, respectively. The maximum relaxation induced by 10(-5) M isoproterenol also decreased significantly in the aortae from the older rats. On the other hand, the ED50 for nitroprusside, nifedipine- and potassium-induced relaxation was not affected by increasing age. These results suggest that ANP-induced relaxation of vascular smooth muscles is reduced with increasing age in rat aortae, rat renal arteries and monkey renal arteries. The mechanisms by which the ANP-induced relaxation decreased in association with the aging process may be quite different from those in acetylcholine-induced and beta adrenoceptor-induced relaxation.     

Thapsigargin inhibits repletion of phenylephrine-sensitive intracellular Ca++ pool in vascular smooth muscles

Thapsigargin (TSG), a putative selective Ca(++)-ATPase inhibitor, has been used to study Ca++ mobilization in many non-excitable cell types. This study aims to determine whether TSG is effective as a selective microsomal Ca++ uptake inhibitor by studying its ability to affect repletion of the phenylephrine (PE)-sensitive Ca++ pool in rat aorta and dog mesenteric artery evaluated by contractility studies. TSG caused a concentration-dependent contraction that was dependent on the concentration of extracellular Ca++. Ca++ influx promoted by TSG was found to occur mostly through L-type Ca++ channels in the dog mesenteric artery but not in the rat aorta. When arterial rings, depleted of their PE-sensitive internal store, were allowed to replete their stores in normal Krebs' solution or in the presence of elevated K+ levels, it was found that repletion was significantly enhanced in the presence of elevated K+. In TSG-treated rings, however, repletion was significantly inhibited under both conditions as indicated by the subsequent PE-induced contraction in Ca(++)-free medium. While the rate of contraction induced by elevated K+ levels was slow immediately after pool depletion in controls, it was rapid in TSG-treated arterial rings. The slow onset of K+ contraction may reflect Ca++ uptake into the pool which was absent in TSG-treated arteries. Differences in the behavior of the two arteries were noted and these may reflect differences in the size of their Ca++ store and their coupling to the extracellular space. Single cells isolated from the dog mesenteric artery were also found to shorten in response to TSG to an amount comparable with that obtained from whole tissue experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergy between thrombin and serotonin in inducing vascular smooth muscle cell proliferation

Previous studies have indicated that apart from playing an important role in hemostasis and thrombosis, thrombin may also contribute to the development of postangioplasty restenosis caused by the stimulation of vascular smooth muscle cell (VSMC) proliferation. Because thrombin generation in vivo is accompanied by platelet activation and release of smooth muscle cell (SMC) growth factors such as serotonin, we examined the possible interaction between these two compounds on VSMC proliferation. Thrombin (0.01 to 100 nmol/L), thrombin receptor-activating peptide (0.1 to 1000 micromol/L), and serotonin (5HT; 0.1 to 1000 micromol/L) increased tritiated thymidine incorporation into the DNA of canine aortic VSMCs in a dose-dependent manner. When thrombin and 5HT were added together at sub-threshold concentrations, they acted synergistically in inducing tritiated thymidine incorporation. These findings were paralleled by a 90%+/-5% increase in the cell number at 48 hours, as compared with a 37%+/-2% increase with 50 micromol/L serotonin and a 13%+/-3% increase with 0.1 nmol/L thrombin. We also demonstrated that a brief exposure to thrombin (1 hour) is sufficient to show its potentiating effect on serotonin. The mitogenic effect of serotonin and its synergistic interaction with thrombin on VSMC proliferation was abolished by serotonin type 2 receptor antagonist LY281067. Similarly, gamma-hirudin--a direct thrombin inhibitor--blocked the mitogenic effect of thrombin and its synergistic interaction with serotonin. When LY281067 and gamma-hirudin were used together, they abolished the mitogenic effects of both the agonists. Because clot-bound active thrombin can escape inactivation by anti-thrombin, this thrombin may potentiate the mitogenic effect of serotonin and keep the SMCs in a proliferative state for a long period of time. These findings support the use of 5HT2 receptor antagonists in combination with thrombin inhibitors in the prevention of SMC proliferation after coronary angioplasty.     

抗血管平滑肌增生和迁移的药物涂层与支架置入后再狭窄

背景：抑制血管平滑肌细胞增殖和血管内膜的增生而不影响血管内皮愈合的药物涂层是研制新型药物洗脱支架和防治支架内再狭窄的新策略。目的：综述抗血管平滑肌细胞增生和迁移药物涂层支架的研究进展。方法：由第一作者应用计算机检索维普数据库中与抗血管平滑肌细胞增生和迁移药物涂层支架置入治疗心血管疾病有关的文献,检索时限1998-01/2011-10。关键词：心血管疾病;药物涂层支架;血管平滑肌;细胞增生;细胞迁移。对资料进行初审,并查看每篇文献后的引文。纳入相关文献25篇,中文15篇,英文10篇。结果与结论：目前临床应用最广的抗血管平滑肌细胞增生和迁移的涂层药物是雷帕霉素和紫杉醇。研究表明,雷帕霉素支架表面携带的雷帕霉素和紫杉醇支架表面携带的紫杉醇均能有效地降低支架置入后再狭窄及临床靶血管血运重建率。目前国内大多数研究仅为小样本、单中心、非随机对照试验,其更长期的疗效和安全性有待更长期的随访和多中心随机对照研究来证明。     

过氧化氢酶过度表达对血管平滑肌细胞增殖的影响

目的:探讨腺病毒载体介导的过氧化氢酶基因转染对体外培养的人血管平滑肌细胞增殖的影响。方法:用含过氧化氢酶基因的重组腺病毒(AdCat)转染人血管平滑肌细胞,应用四甲基偶氮唑蓝(MTT)方法观察血管平滑肌细胞的增殖活性,同时用流式细胞术观察血管平滑肌细胞细胞周期的变化。结果:MTT比色法分析显示AdCat组明显抑制细胞增殖,与对照组相比差异有显著性(P<0.05);细胞周期分析发现AdCat组G0/G1期分布百分率显著高于对照组,而S、G2/M期分布百分率显著低于对照组,细胞增殖能力下降(P<0.05)。结论:腺病毒载体介导的过氧化氢酶基因转染能抑制人血管平滑肌细胞的增殖。     

同型半胱氨酸对大鼠血管平滑肌细胞增殖及胶原生成的影响

目的:观察同型半胱氨酸的浓度对Ⅰ,Ⅲ,Ⅳ和Ⅵ型胶原的产生以及大鼠血管平滑肌细胞增殖效应的影响。方法:实验于2005-02/2006-04在瑞金医院心内科实验室完成。①采用组织块贴壁法原代培养大鼠胸主动脉平滑肌细胞,用不同浓度的同型半胱氨酸(0.025,0.05,0.1,0.2,0.5,1.0,1.5,2.0,3.0,5.0 mmol/L)刺激大鼠血管平滑肌细胞,并设对照孔(未加同型半胱氨酸)和空白孔(未加细胞)作对照。②分别作用12,24,48,72h,以四甲基偶氮唑盐法检测同型半胱氨酸对平滑肌细胞的活性细胞数量及细胞增殖情况;以5溴-2脱氧尿苷法检测同型半胱氨酸对大鼠血管平滑肌细胞DNA合成的作用;流式细胞仪观察细胞周期的变化;酶联免疫法测定胶原的含量。结果:①细胞增殖情况:在0.025,0.05 mmol/L的同型半胱氨酸浓度刺激下,12～48h血管平滑肌细胞增殖增加明显。②细胞DNA合成:与四甲基偶氮唑盐结果类似,24～48h时,在浓度为0.025,0.05 mmol/L的同型半胱氨酸刺激下细胞合成DNA增加(24h:432±33,774±52;48h:582±32,816±62),其促增殖作用增强(P<0.05);随着浓度的增加,大鼠血管平滑肌细胞合成DNA开始下降,至5 mmol/L浓度时最低。③细胞周期的变化:24h时在浓度为0.025,0.05 mmol/L的同型半胱氨酸刺激下增殖的细胞S期的百分含量较对照组和同型半胱氨酸其他浓度组明显增加。④胶原的含量:细胞的Ⅰ型和Ⅳ型胶原分泌随着同型半胱氨酸浓度的升高呈现剂量依赖性的增高模式。Ⅲ型胶原有轻度的升高,无统计学上意义。高浓度的同型半胱氨酸会减少Ⅵ型胶原的分泌,并呈剂量依赖性(r2=0.41;P<0.001)。结论:较低浓度的同型半胱氨酸刺激大鼠血管平滑肌细胞的增殖加速;并可能通过改变纤维斑块中的胶原构成类型导致了斑块的不稳定性和易损性,最终加速了粥样斑块的发生和发展。     

Effects of 2-deoxy-D-glucose on proliferation of vascular smooth muscle cells and endothelial cells

2-Deoxy-D-glucose (2-DG) is a glucose analogue that has been proposed for cancer therapy due to its cytostatic properties. Its effect on the proliferation of smooth muscle cells and endothelial cells has not been fully clarified. The aims of this study were to investigate the effects of 2-DG on the proliferation of porcine aortic endothelial cells (PAEC) and porcine smooth muscle cells (PSMC), to establish an overview of its dose-dependent inhibitory capacity and to examine whether the short-term incubation of cells with 2-DG has an impact on cell proliferation in culture. Our results showed a dose-dependent significant inhibitory effect on proliferation, which was more pronounced in PSMC than in PAEC. Even after short-term incubation of cells with 2-DG, relevant inhibition of proliferation was documented. The clinical application of 2-DG might be a promising concept by inhibiting cells that show a potentially rapid proliferation in response to non-malignant stimuli, such as smooth muscle cells after intracoronary stenting.     

超声造影剂对血管平滑肌细胞增殖、迁移和凋亡的影响

目的探讨超声波联合超声造影剂对平滑肌细胞增殖、迁移和凋亡的影响.方法体外培养大鼠胸主动脉血管平滑肌细胞（VSMC）.采用MIT法、Millicell小室、Annexin V-FITC/PI双标染色和流式细胞仪,检测VSMC的增殖、迁移能力和凋亡,观察血小板衍生生长因子--BB（PDGF-BB）对VSMC增殖、迁移和凋亡的影响,频率1 MHz、声强0.3 W/cm^2的连续波超声联合声学造影剂辐照VSMC后上述指标的变化.结果PDGF-BB对VSMC的凋亡无影响,但可促进VSMC增殖和迁移.超声联合造影剂辐照VSMC 30 s即可显著抑制PDGF-BB所致的VSMC增殖（P〈0.05）,同时细胞凋亡比例显著增高（P〈0.01）,辐照60 s可显著抑制PDGF-BB所致的VSMC迁移（P〈0.05）,随着辐照时间延长,以上作用增强,辐照60 s时对VSMC增殖的抑制程度最强.结论低强度超声波辐照联合超声造影剂可抑制VSMC增殖、迁移,并促进细胞凋亡.     

血管平滑肌细胞增殖及分泌内皮素水平与氯沙坦和依拉普利的影响

目的：观察血管紧张素Ⅱ AT1受体阻滞剂氯沙坦及转换酶抑制剂依拉普利对培养的血管平滑肌细胞增殖的抑制作用及对血管平滑肌细胞分泌内皮素水平的影响。方法：实验于2004-03／11在华中科技大学生命学院生物物理与生物化学研究所实验室及武汉市七医院检验科完成。取大白鼠腹主动脉平滑肌细胞，用贴块法进行血管平滑肌细胞原代培养，进行消化传代后,取生长状态良好的3-6代血管平滑肌细胞，分别用含0．1，1．0，10，100μmol／l。不同浓度的氯沙坦（氯沙坦组）和依拉普利（依拉普利组）的培养液培养，测定细胞倍增时间（T1=t[log2／（logN1-logN0）]，TD：细胞倍增时间，t：培养时间，No：接种后的细胞数，M：培养t小时后的细胞数），进行细胞增殖核抗原免疫组织化学检测，并计算增殖指数（增殖指数=增殖细胞核抗原阳性细胞核个数／400）。用均相竞争放射免疫分析法测定血管平滑肌细胞上清液内皮素-1的含量。 结果：①培养的血管平滑肌细胞倍增时间：随氯沙坦和依拉普利浓度的逐渐增加，血管平滑肌细胞倍增时间逐渐延长（P〈0．01），两组比较差异无显著性意义（P〉0．05）。②增殖指数：氯沙坦组和依拉普利组增殖指数均显著降低（P〈0．05或P〈0．01），且呈剂量依赖性，两组间比较差异无显著性意义（P〉0．05）。③培养的血管平滑肌细胞上清液内皮素-1的含量：氯沙坦组和依拉普利组在一定剂量范围内（氯沙坦组0．1～100μmol／L，依拉普利组1．0～100μmol／L）内皮素水平显著降低（P〈0．05或P〈0．01），两组之间比较，氯沙坦组显著低于依拉普利组（P〈0．05）。 结论：血管紧张素ⅡAT1受体抑制氯沙坦与血管紧张素转换酶抑制剂依拉普利均能有效抑制体外培养的血管平滑肌细胞增殖，两者作用差异无显者性，氯沙坦和依拉普利均能有效降低血管平滑肌细胞分泌内皮素水平，前者作用更显著。     

血管平滑肌细胞增殖及分泌内皮素水平与氯沙坦和依拉普利的影响

目的:观察血管紧张素ⅡAT1受体阻滞剂氯沙坦及转换酶抑制剂依拉普利对培养的血管平滑肌细胞增殖的抑制作用及对血管平滑肌细胞分泌内皮素水平的影响。方法:实验于2004-03/11在华中科技大学生命学院生物物理与生物化学研究所实验室及武汉市七医院检验科完成。取大白鼠腹主动脉平滑肌细胞,用贴块法进行血管平滑肌细胞原代培养,进行消化传代后,取生长状态良好的3～6代血管平滑肌细胞,分别用含0.1,1.0,10,100μmol/L不同浓度的氯沙坦(氯沙坦组)和依拉普利(依拉普利组)的培养液培养,测定细胞倍增时间(TD=t犤log2/(logNt-logN0)犦,TD:细胞倍增时间,t:培养时间,No:接种后的细胞数,Nt:培养t小时后的细胞数),进行细胞增殖核抗原免疫组织化学检测,并计算增殖指数(增殖指数=增殖细胞核抗原阳性细胞核个数/400)。用均相竞争放射免疫分析法测定血管平滑肌细胞上清液内皮素-1的含量。结果:①培养的血管平滑肌细胞倍增时间:随氯沙坦和依拉普利浓度的逐渐增加,血管平滑肌细胞倍增时间逐渐延长(P<0.01),两组比较差异无显著性意义(P>0.05)。②增殖指数:氯沙坦组和依拉普利组增殖指数均显著降低(P<0.05或P<0.01),且呈剂量依赖性,两组间比较差异无显著性意义(P>0.05)。③培养的血管平滑肌细胞上清液内皮素-1的含量:氯沙坦组和依拉普利组在一定剂量范围内(氯沙坦组0.1～100μmol/L,依拉普利组1.0～100μmol/L)内皮素水平显著降低(P<0.05或P<0.01),两组之间比较,氯沙坦组显著低于依拉普利组(P<0.05)。结论:血管紧张素ⅡAT1受体抑制氯沙坦与血管紧张素转换酶抑制剂依拉普利均能有效抑制体外培养的血管平滑肌细胞增殖,两者作用差异无显者性,氯沙坦和依拉普利均能有效降低血管平滑肌细胞分泌内皮素水平,前者作用更显著。     

miRNA-146a调控血管平滑肌细胞增殖和凋亡的作用及机制

目的探究miRNA-146a调控血管平滑肌细胞增殖、凋亡的作用及相关机制。方法取SDP级健康雄性SD大鼠作为实验对象,取血管平滑肌细胞(VSMC)消化离心后,转染50nmol/L miRNA-146a反义寡核苷酸、错义链和同等剂量磷酸盐缓冲液(PBS),进行对照比较。结果实验组细胞在转染后48h内VSMC的数目和吸光度值均低于其他两组,细胞凋亡率明显高于其他两组,核因子κBp65、PCNA的表达水平低于其他两组,差异均具有统计学意义(P0.05)。结论miRNA-146a可促进VSMC的增殖,抑制细胞凋亡的进行,这一作用机制与核因子κBp65、PCNA表达水平增高有关。     

丹皮酚对血管平滑肌细胞增殖和迁移的影响及作用机制

目的 检测丹皮酚对于血管平滑肌细胞(VSMC)增殖和迁移的影响并探究其作用机制。方法 通过氧化修饰的低密度脂蛋白(ox-LDL)处理人VSMC在体外建立动脉粥样硬化的细胞模型。使用Western blot检测高迁移率族蛋白B1(HMGB1)的表达水平,HMGB1 mRNA的表达水平则由实时定量PCR法测定。应用酶联免疫吸附法测定细胞上清液中炎性因子肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)的含量;应用CCK-8实验检测VSMC的增殖活性;应用Transwell细胞迁移实验检测VSMC的迁移能力。结果 丹皮酚显著降低ox-LDL导致的VSMC上清液中炎性因子TNF-α、IL-1β和IL-6的含量;丹皮酚显著减弱VSMC的增殖活性和迁移能力;丹皮酚下调HMGB1在蛋白质和mRNA上的表达水平,补充HMGB1可减弱丹皮酚对抗VSMC功能紊乱的作用。结论 丹皮酚通过下调HMGB1减轻ox-LDL导致的VSMC炎症反应,并因此抑制了VSMC的增殖和迁移,对动脉粥样硬化的发生、发展具有抑制作用。