Edaravone, a radical scavenger, may enhance or produce antiproliferative effects of fluvastatin, amlodipine, ozagrel, GF109203X and Y27632 on cultured basilar artery smooth muscle cells

Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10-100 microM and 0.1-1 microM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 microM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 microM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10-100 microM, 1-10 microM and 0.1-1 microM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.     

依达拉奉对急性脑梗死患者血清超敏C-反应蛋白、内皮素、基质金属蛋白酶及神经元特异性烯醇化酶水平的影响

目的 探讨急性脑梗死患者血清中超敏C-反应蛋白(hs-CRP)、内皮素(ET)、基质金属蛋白酶(MMP-9)和神经元特异性烯醇化酶(NSE)水平变化及依达拉奉对它们的影响.方法 选择急性脑梗死患者100例,随机分为常规治疗组和依达拉奉组.依达拉奉组是在常规治疗基础上给予依达拉奉30mg静脉滴注,2次/d,连续14d.检测两组治疗前、后血清hs-CRP、ET、MMP-9及NSE水平和神经功能缺损的变化.结果 与常规治疗组比较,依达拉奉组血清hs-CRP、ET、MMP-9及NSE水平明显降低(P＜0.05),神经功能缺损评分也明显低于常规治疗组(P＜0.05).结论 急性脑梗死患者血清中hs-CRP、ET、MMP-9及NSE水平升高,依达拉奉可以降低它们的水平,能有效改善急性脑梗死的神经功能缺损程度.     

尤瑞克林联合依达拉奉对急性脑梗死患者血清同型半胱氨酸、血清超敏C-反应蛋白及D-二聚体水平的影响

目的 探讨尤瑞克林联合依达拉奉对急性脑梗死患者血清同型半胱氨酸（Hcy）、血清超敏C-反应蛋白（hs-CRP）和D-二聚体水平的影响。方法 将河南大学附属南阳南石医院自2015年1月-2017年10月收治的急性脑梗死患者160例作为研究对象,随机分为两组,观察组86例给予尤瑞克林联合依达拉奉进行治疗,对照组74例单纯给予依达拉奉进行治疗,两组均治疗2周。对比观察两组患者的治疗效果和血清Hcy、hs-CRP和D-二聚体水平变化情况。结果 观察组患者治疗后临床总有效率为91.86%,显著高于对照组的79.73%,差异有统计学意义（P<0.05）。治疗后两组患者Hcy、hs-CRP和D-二聚体水平及NIHSS评分均显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组以上指标显著低于对照组,差异有统计学意义（P<0.05）。结论 对急性脑梗死患者在常规治疗的基础上使用尤瑞克林联合依达拉奉治疗,可有效改善患者临床效果、神经功能恢复,降低血清炎症介质的水平,达到改善预后的目的,可推广使用。     

Effects of angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, 3-hydroxy-3-methyl glutaryl (HMG) CoA reductase inhibitors, amlodipine and epalrestat on cultured basilar artery smooth muscle cell proliferation

Proliferation of vascular smooth muscle cells (VSMC) stimulated by oxidative stresses and reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. Antiatherosclerotic effects of angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, HMG CoA reductase inhibitors, calcium channel blocker and epalrestat were studied with an in vitro guinea-pig basilar artery smooth muscle cell (GBa-SM3) culture system over 3 days incubated with 0 to 10% of fetal bovine serum. Results demonstrated that simvastatin (0.1 mM), fluvastatin (0.3 mM), amlodipine (0.2 mM) and epalrestat (1 mM) elicited significant (p < 0.05 or 0.01) antiproliferative effects, whereas losartan (1 mM), valsartan (1 mM), enalapril (0.1 mM), captopril (1 mM), trandolapril (0.01 mM), pravastatin (0.7 mM) did not. In conclusion, the present in vitro VSMC culture system may serve as a comprehensive screening method for pleiotropic effects of commonly used therapeutic agents.     

血浆Lp-PLA2,Hcy与急性脑梗死患者颈动脉硬化的相关性研究

目的观察急性脑梗死患者血浆脂蛋白磷脂酶A2（Lp-PLA2）,同型半胱氨酸（Hcy）与患者颈动脉硬化的相关性。方法选取80例急性脑梗死患者为观察组,40例健康人作为对照组。测定所有人血浆Lp-PLA2和Hcy的浓度,并且测定观察组患者颈动脉内膜中层厚度（IMT）。结果与对照组比较,观察组患者血浆的Lp-PLA2和Hcy均明显升高,两组比较有显著性差异（P〈0.01）。观察组患者的IMT为（1.42±0.51）mm,与Lp-PLA2有明显正相关关系（r=0.315,P〈0.01）;与Hcy有明显正相关关系（r=0.427,P〈0.01）。结论联合检测血浆Lp-PLA2,Hcy水平,可作为判断急性脑梗死患者疾病严重程度、临床疗效及评估预后的重要参数。     

TMB—8抑制组胺,5—羟色胺和谷氨酸引起的培养乳牛基底动脉平滑肌细 …

AIM: To study the effects of 8-(N,N-diethylamino)-n-octyl-3,4,5- trimethoxybenzoate (TMB-8) on intracellular free calcium ([Ca2+]i) in cultured calf basilar artery smooth muscle cells. METHODS: [Ca2+]i was examined by a system of measurement of AR-CM-MIC, using Fura 2-AM as a fluorescent indicator. RESULTS: In the presence of extracellular Ca2+ 1.3 mmol.L-1, histamine (His), serotonin (5-HT), and sodium glutamate (Glu) markedly increased the [Ca2+]i which was attenuated by TMB-8. In Ca2+ free Hanks' solution containing egtazic acid 0.1 mmol.L-1, TMB-8 not only reduced the resting [Ca2+]i, but also inhibited the elevation of [Ca2+]i evoked by His and 5-HT. CONCLUSION: TMB-8 reduced the resting [Ca2+]i and attenuated His-, 5-HT-, and Glu-induced increases of [Ca2+]i in basilar artery smooth muscle cells.     

Stimulatory effects of squamocin,an Annonaceous acetogenin,on Ca(2+)-activated K+ current in cultured smooth muscle cells of human coronary artery

The patch-clamp recording technique was used to investigate the effect of squamocin, an Annonaceous acetogenin, on ion currents in cultured smooth muscle cells of human coronary artery. In whole-cell configuration, squamocin (0.3-100 microM) induced Ca(2+)-activated K+ current [IK(Ca)] in a concentration-dependent manner with an EC50 value of 4 microM. Squamocin-stimulated IK(Ca) was suppressed by iberiotoxin (200 nM), paxilline (1 microM), or tetraethylammonium chloride (5 mM), yet not by apamin (200 nM) or glibenclamide (10 microM). In cells dialyzed with 10 mM EGTA, this compound had little effect on IK(Ca). When cells were exposed to Ca(2+)-free solution, squamocin (3 microM) induced a transient increase in IK(Ca). In continued presence of squamocin, an additional increase in extracellular Ca2+ (1 mM) caused a significant increase in IK(Ca). Pretreatment with carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 3 microM) for 5 h did not alter the magnitude of squamocin-induced IK(Ca). However, squamocin (30 microM) suppressed the amplitude of voltage-dependent L-type Ca2+ current. In cell-attached configuration of single-channel recordings, squamocin applied to the bath increased the activity of large-conductance Ca(2+)-activated K+ (BKCa) channels without altering single-channel conductance. Conversely, in inside-out patches, squamocin applied to the intracellular surface had no effect on BKCa channel activity, whereas niflumic acid increased it effectively. These findings provide the evidence that squamocin can activate IK(Ca) in coronary arterial smooth muscle cells. Initial transient activation of IK(Ca) may reflect the squamocin-induced Ca2+ release from intracellular Ca2+ stores, whereas the sustained activation of IK(Ca) may arise from the squamocin-induced Ca2+ influx across the cell membrane. The stimulatory effect of squamocin on these channels should affect the functional activity of vascular smooth muscle cells.