心脉隆注射液对不同状态大鼠离体胸主动脉的影响

摘 要 目的：探讨心脉隆注射液（XML）对不同状态大鼠离体胸主动脉的影响。方法: 采用累积加药法,观察XML对静息、氯化钾（KCl）或去甲肾上腺素（NA）预收缩大鼠离体胸主动脉的影响。使用不同工具药分析作用产生的机制。结果: 与对照组相比,XML在一定浓度范围内可以兴奋静息离体胸主动脉,进一步增加KCl预收缩血管的张力,而降低NA预收缩血管的张力。XML舒张NA预收缩血管的作用可被普萘洛尔、双氯芬酸所抑制,而不受Nω-硝基-L-精氨酸的影响。结论:XML对不同状态下大鼠离体胸主动脉的作用不同,其机制可能与Ca²+通道、β受体和前列腺素有关。     

脉炎消口服液对人脐动脉平滑肌细胞增殖的影响及其机制

目的:探讨脉炎消口服液在体外对人脐动脉平滑肌细胞(HUASMCs)增殖的影响及其作用机制。方法:体外组织贴块培养HUASMCs,并传2³代,免疫组化法进行鉴定;采用MTT法观察不同体积分数脉炎消口服液(0.4%、4%、40%)对HUASMCs细胞增殖的抑制作用;采用RT-PCR法检测不同体积分数脉炎消口服液(0.4%、4%、40%)对HUASMCs细胞IL-6 mRNA表达水平的影响。结果:组织块贴壁法原代培养HUASMCs,传3代后,阳性细胞率为90%;脉炎消口服液对HUASMCs的增殖具有明显的抑制作用,且体积分数在一定范围内(0.4%3代,免疫组化法进行鉴定;采用MTT法观察不同体积分数脉炎消口服液(0.4%、4%、40%)对HUASMCs细胞增殖的抑制作用;采用RT-PCR法检测不同体积分数脉炎消口服液(0.4%、4%、40%)对HUASMCs细胞IL-6 mRNA表达水平的影响。结果:组织块贴壁法原代培养HUASMCs,传3代后,阳性细胞率为90%;脉炎消口服液对HUASMCs的增殖具有明显的抑制作用,且体积分数在一定范围内(0.4%⁴0%)呈浓度依赖性。结论:脉炎消口服液抑制HUASMCs增殖的作用是通过下调细胞IL-6mRNA的表达水平而实现的。     

心脉隆注射液的药理作用和临床疗效

心脉隆注射液 (原名心脉龙注射液 )是一种从蟑螂体内提取制成的含生物活性物质———复合核苷类和粘氨酸的中药静脉注射制剂。本文就心脉隆注射液的药理作用和临床疗效等综述如下。1　药理作用主要表现在心血管方面 ,所含两种活性成分相互作用而产生药理机制尚未清楚。大量实验初步推测 ,其中复合核苷类化合物起主要作用 ,粘氨酸通过体内的水解达到辅助作用 ,二者缺一不可。1.1　强心作用　方春生等 (1990年 )报道 :药理实验研究证实 ,其对正常 ,尤其是衰竭离体猫乳头肌具有正性肌力作用 ;张华明等 (1990年 )报道 :对麻醉猫在体衰竭的心肌也…     

心脉隆注射液治疗心力衰竭的疗效及药理作用机制的研究进展

心脉隆注射液作为临床治疗心力衰竭的一种新型药物,有效成分主要为复合氨基酸、核苷、多肽等。体外研究结果发现,心脉隆注射液对心血管系统的作用是多方面的,如持久、温和地增加心肌收缩力,改善心肌细胞钙离子内流;扩张冠状动脉,让血流量增加,对氧自由基引起的心肌损伤进行抑制;扩张血管,让体动脉压、肺毛细血管内压、肺动脉压降低;对神经内分泌失衡进行纠正,让血浆降钙素基因肽含量增加;对内皮素的作用和分泌进行移植;对肾血管进行扩张,让肾血流量增加;对心律失常进行防治,利尿等。现阶段临床在对各种因素引起的心力衰竭进行治疗时,心脉隆注射液得到了非常广泛的应用。本研究主要分析心脉隆注射液治疗心力衰竭的疗效及药理作用机制。     

槲皮素对兔离体肠平滑肌张力的影响及其机制

目的:观察槲皮素对兔离体回肠平滑肌肌张力的影响,并探讨其作用机制。方法:试验采用经典的离体小肠灌流技术,观察槲皮素(quercetin,Que)对回肠平滑肌自主收缩活动以及乙酰胆碱(acetylcholine,Ach)、氯化钡及组胺(histamine)所致痉挛性收缩肠平滑肌张力的影响。结果:槲皮素(20,60,100mol.L-1)能剂量依赖性的抑制家兔离体小肠平滑肌自发性收缩,对乙酰胆碱,组胺和氯化钡所致的兔离体肠痉挛性收缩也具有剂量依赖性抑制作用。在无钙台式液中,槲皮素可明显抑制Ach引起的回肠平滑肌收缩(P<0.01),亦能使氯化钙量效曲线下移。槲皮素对Bay K8644(0.5mol.L-1)引起的回肠平滑肌收缩亦有明显抑制作用(P<0.01)。结论:槲皮素明显抑制了家兔离体小肠平滑肌的收缩活动,其机制与抑制外钙内流及内钙释放有关。     

心脉隆注射液治疗慢性心力衰竭的临床观察

目的 观察心脉隆注射液对慢性心力衰竭患者心脏左室射血分数（LVEF）、B型利钠肽（BNP）的影响.方法 选择2012年11月～2013年4月在本院住院治疗的慢性心力衰竭患者41例（心功能分级Ⅱ～Ⅳ级）,将其分成治疗组及对照组,对照组患者给予常规治疗,治疗组患者在此基础上加用心脉隆注射液＋0.9％氯化钠溶液200 ml静脉滴注,比较两组的治疗效果.结果 经治疗后,治疗组患者的中心静脉压与BNP水平均明显低于对照组（P＜0.05）,症状明显改善;而LVEF则明显高于对照组（P＜0.05）,且用药过程中无明显不良反应发生.结论 心脉隆注射液可降低慢性心力衰竭患者心脏负荷,抑制神经分泌激活,显著改善心功能.     

单脐动脉对妊娠的影响及其临床意义

目的：探讨单脐动脉对妊娠的影响及其临床意义。方法：回顾性分析2008年6月～2009年6月在本院行产前超声检查发现合并单脐动脉50例患者的临床资料,总结该组患者的临床情况及妊娠结局。结果：该组患者中早产8例,剖宫产27例,新生儿畸形8例,胎儿生长受限4例,胎死宫内2例,染色体异常3例,15例胎儿妊娠进程顺利,随访无明显异常发现。结论：单脐动脉为高危妊娠,产前需密切监测胎儿成长,在排除胎儿染色体异常或合并其他畸形时,可以考虑继续妊娠。     

心脉隆注射液对老年慢性心力衰竭患者脑钠肽前体及肌钙蛋白Ⅰ的影响

目的：探讨心脉隆注射液对老年慢性心力衰竭（ CHF ）患者脑钠肽前体（ proBNP ）及肌钙蛋白I （ CTnⅠ）的影响。方法收集医院70岁以上CHF住院患者92例,随机分为两组。对照组43例予CHF常规治疗;心脉隆组49例在CHF常规治疗基础上加用心脉隆注射液300 mg/d静脉滴注治疗14 d。治疗前后分别检测患者proBNP及CTnⅠ水平、6 min步行试验（6MWT ）距离。结果92例患者中,随着NYHA心功能分级增加,患者proBNP及CTnⅠ水平均上升,而6MWT距离下降;治疗14 d后,两组患者proBNP及CTnⅠ水平均较治疗前降低,6MWT距离较治疗前增加;治疗后心脉隆组患者较对照组患者proBNP更低[（410.97±74.56） pg/mL比（476.75±80.21）pg/mL, P=0.000],CTnⅠ亦更低[（0.06±0.03） ng/mL比（0.08±0.04） ng/mL,P=0.008],而6MWT距离[（431.78±42.58） m比（406.25±46.31）m,P=0.007]较对照组增高。结论心脉隆注射液能改善老年CHF患者的心功能。     

Effects of reserpine on nerve stimulation-induced constrictions in canine isolated splenic artery

1. Our previous studies have demonstrated that peri-arterial electrical nerve stimulation (PNS) of the canine splenic artery induces a double-peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor-mediated constriction, followed by a prolonged, mainly alpha1-adrenoceptor-induced response. In the present study, we examined the effects of reserpine on PNS-induced double-peaked responses. 2. The vasoconstrictor response to tyramine was abolished after reserpine treatment, but the responses to noradrenaline (NA) and ATP were not significantly modified. 3. The PNS-induced second peak vasoconstrictor responses were markedly reduced in reserpinized vessels, whereas the first peak vasoconstrictor responses were not so strongly influenced (i.e. they were not significantly affected at 1 Hz, but were significantly affected at 4 and 10 Hz). 4. All reserpine-resistant responses were unaffected by treatment with prazosin, but were abolished by subsequent application of alpha,beta-methylene ATP. The exposure of reserpine-treated tissues to NA almost completely restored tyramine-induced vasoconstriction and the second neurogenic peak vasoconstrictor response, but failed to affect the first neurogenic response. 5. The present results indicate that ATP and NA are cotransmitters responsible for the double-peaked vasoconstrictor responses of canine splenic artery. In addition, it is suggested that PNS causes NA release not only from intragranular NA storage sites, but also from tyramine-sensitive cytoplasmic sites.     

普纳替尼对人血管内皮细胞功能的影响

目的 观察普纳替尼(Ponatinib)对人血管内皮细胞的增殖、迁移、血管形成及NO合成释放的影响, 从细胞水平评价Ponatinib血栓不良反应形成机制。方法 采用CCK-8法、体外划痕法、Matrigel基底膜成管法及NO检测试剂盒分别考察Ponatinib对人脐静脉内皮细胞(HUVECs)的细胞毒作用、迁移能力、血管形成能力及细胞NO释放水平的影响。结果 研究表明Ponatinib对HUVECs细胞半数抑制浓度(IC₅₀)为(0.69±0.05)μmol/L。非毒性剂量的Ponatinib能够不同程度抑制HUVECs细胞的迁移、血管形成及NO的释放(P<0.05)。结论 Ponatinib通过影响人血管内皮细胞增殖、迁移、血管形成等正常功能而造成血管内皮损伤, 可能为其诱发血栓的原因之一。     

Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery

Recent studies have shown that testosterone induces relaxation of different arteries, although the mechanism of this action is still under debate. We investigated the involvement of potassium channels in this mechanism. Using standard organ bath techniques, rings of human umbilical arteries (HUA) without endothelium were contracted by serotonin (5-HT, 1 μM), histamine (10 μM) and potassium chloride (KCl, 30 and 60 mM), and the vasorelaxant effect of testosterone was analysed. Testosterone (100 μM) relaxed human umbilical arteries contracted with 5-HT (30.1 ± 3.2%), histamine (55.1 ± 2.6%), KCl 30 mM (52.9 ± 8.3%) and KCl 60 mM (54.8 ± 6.3%). Flutamide (10 μM), an inhibitor of classical intracellular testosterone receptor, and glibenclamide, an ATP-sensitive potassium-channels (K_ATP) inhibitor, did not influence the testosterone relaxant effect. 4-aminopyridine, a voltage-sensitive potassium-channels (Kv) inhibitor, decreased the effect of testosterone on histamine- and 5-HT-contracted arteries. Tetraethylammonium (TEA), which inhibits Kv channels and large-conductance Ca²⁺-activated potassium channels (BK_Ca), decreased the effect of testosterone on KCl (60 mM)-contracted and 5-HT-contracted HUA. In conclusion, testosterone induces relaxation of HUA, and this effect does not appear to be mediated via a classic intracellular testosterone receptor-dependent mechanism. Our results suggest that this relaxation is partially mediated by activation of BK_Ca and K_V channels. The involvement of these two channels in testosterone-relaxant mechanism is dependent on the pathways activated by the contractile agent used.     

妊娠期糖尿病并发子痫前期对脐动脉血流的影响

目的 探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)并发子痫前期(preeclampsia,PE)对胎儿脐动脉血流的影响.方法 选取某院产妇165例,其中妊娠期糖尿病(GDM)并发子痫前期(PE)孕妇76例(观察组)及妊娠期糖尿病(GDM)孕妇89例(对照组),应用彩色多普勒超声收集两组患者的胎儿脐动脉(UA)收缩末期最大血流速度和舒张末期最大血流速度比值(S/D值)、搏动指数(PI)、阻力指数(RI)等资料,并观察胎儿宫内发育情况及出生时新生儿情况(出生时体重,1分钟阿氏评分).结果 观察组的S/D值、PI、RI值均高于对照组(P＜0.05),观察组1分钟阿氏评分较对照组低(P＜0.05);两组胎儿宫内发育情况(包括双顶径、腹围、股骨径)及新生儿体重比较差异无统计学意义(P＞0.05).结论 妊娠期糖尿病并发子痫前期对胎儿脐动脉血流及胎儿出生后1分钟阿氏评分具有一定的影响,因此应用彩色多普勒超声观察胎儿脐动脉血流情况,有助于判断妊娠期糖尿病孕妇是否并发子痫前期.     

5-HT1D receptor agonists and human coronary artery reactivity in vitro: crossover comparisons of 5-HT and sumatriptan with rizatriptan and L-741,519

1Rizatriptan (MK-462, (N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine)) and its structurally related analogue L-741,519 (N-methyl-4-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]piperidine) are novel 5-HT_1D-receptor agonists. Rizatriptan has shown efficacy as an anti-migraine agent in clinical trials. Since angiographic studies in patients have shown that sumatriptan (an established 5-HT_1D-receptor agonist) can cause coronary artery vasoconstriction, we compared the effects of rizatriptan and L-741,519 with those of 5-HT and sumatriptan on endothelium-denuded segments of human coronary artery in vitro. 2Coronary arteries were obtained from explanted hearts from patients undergoing cardiac transplantation (n=16 viable arteries from 13 males, 3 females, aged 38–68 years) and arterial segments (5–6 mm in length) were mounted in organ baths for isometric tension recording. Each segment was first exposed to 45mm KCl and then to 5-HT (1 nm–100 μm). Concentration–effect curves to rizatriptan and sumatriptan (Study 1, n=6 or 7 arteries) or sumatriptan and L-741,519 (Study 2, n=8 arteries) were then performed in a consecutive and random manner. The response to repeated application of 5-HT was obtained in separate segments. 3One artery showed severe atheroma and was not included in the analysis. ANOVA showed that 5-HT responsiveness varied significantly between arteries from different patients, but not between arterial segments from the same patient. Desensitization was seen consistently across all agonists but did not significantly affect inter-agonist comparisons. 4There was graded effectiveness in the ability of the agonists to cause contraction with the rank order of E_max values being 5-HTsumatriptan>L-741,519>rizatriptan. In terms of EC₅₀ values, L-741,519 was significantly more potent than sumatriptan. 5The present study (using a ‘cross-over’ experimental protocol) confirms our previous observation that rizatriptan is less effective than sumatriptan in causing contraction of human isolated coronary artery. Furthermore, it shows that the lower maximum contractile response to rizatriptan, compared with that of sumatriptan, is not merely the consequence of variability in response to 5-HT_1D- receptor agonists between patients or between segments from the same artery.     

胎儿单脐动脉的超声诊断及其临床价值（附24例分析）

目的探讨胎儿单脐动脉畸形产前超声声像图特征及其临床意义。方法回顾性分析2007年11月至2008年12月我院产前超声检查发现的24例胎儿单脐动脉的临床和超声资料。结果24例超声均诊断为胎儿单脐动脉,超声显示在胎儿盆腔膀胱及脐轮斜切面仅见膀胱一侧显示脐动脉走行。其中合并胎儿其他系统发育异常8例;继续妊娠的16例中,有4例在孕程和产程中出现各种异常,余12例胎儿妊娠进程顺利,随访无明显异常发现。结论彩色多普勒超声检查能够准确诊断胎儿单脐动脉,超声检查发现胎儿单脐动脉时需多角度动态观察以明确是否合并其他器官的发育畸形,对于继续妊娠者需密切注意胎儿发育情况和产程。     

单脐动脉综合征产前诊断及预后

目的通过孕中期常规检查,尽早发现胎儿单脐动脉,对B超诊断单脐动脉综合征胎儿进一步行产前诊断,观察畸形情况,预测其预后。方法超声提示单脐动脉胎儿行磁共振(MRI)、染色体检查,引产胎儿进行尸体解剖,活胎远期随访。结果本院2006年6月至2007年11月产前超声检查7938例,发现单脐动脉的胎儿72例,发生率0.9%;单脐动脉综合征合并其他畸形的发生率达66.7%;其中合并1种畸形占22.5%,合并2种畸形占30%,≥3种畸形占47.5%。种类包括染色体异常,心脏、颅脑、肾脏、输尿管、膈肌、腹壁、四肢、肛门、脊柱畸形以及表型的其他异常。经超声提示单脐动脉后行MRI共有31例,23例与超声结果相符,8例与超声结果有差异。脐血染色体检查诊断出胎儿染色体异常4例。结论超声检查易及早诊断单脐动脉综合征,该综合征具有胎儿高风险的畸形率,需MRI进一步产前诊断。对产前诊断提示单脐动脉综合征合并1种及其以上畸形者建议胎儿染色体检查,经超声、MRI未发现其他异常合并者可出生后婴儿行染色体检查。但通过超声、MRI、脐血染色体检查诊断未发现胎儿合并有其他异常者胎儿其出生后仍有异常可能。     

Modeling placental transport: Correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984–991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport across the BeWo cells was observed in the rank order of caffeine > antipyrine > benzoic acid > glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare the two experimental models. The results from the in vitro studies were in excellent agreement with the ex vivo results (caffeine ≈ antipyrine > benzoic acid > glyphosate). However the transfer rate was much slower in the BeWo cells compared to the perfusion system. The advantages and limitations of each model are discussed in order to assist in the preparation, prediction, and performance of future studies of maternal–fetal transfer.     

微RNA-24对过氧化氢诱导的人脐静脉血管内皮细胞凋亡的影响及作用机制

目的探讨微RNA-24(miR-24)对H2O2诱导的人脐静脉血管内皮细胞(HUVEC)存活、迁移和凋亡的影响及作用机制。方法通过转染miR-24高表达、miR-24抑制物(anti-miR-24)及其阴性对照慢病毒质粒(miR-24 NC)构建稳转细胞,3种细胞用H2O2500μmol·L^-1处理12 h。采用四甲基偶氮唑盐(MTT)法检测细胞存活率,划痕实验检测细胞迁移率,Hoechst33258染色及流式细胞术检测细胞凋亡,实时荧光定量聚合酶链反应(qRT-PCR)检测miR-24,Bax,Bcl-2和胱天蛋白酶3 mRNA表达水平,Western印迹法和免疫细胞化学法检测Bax、Bcl-2和胱天蛋白酶3蛋白表达水平。结果与miR-24 NC组比,miR-24高表达组miR-24表达升高(P<0.05),而anti-miR-24组降低(P<0.05)。与正常对照组比,H2O2组细胞凋亡率增加(P<0.05)、细胞存活和迁移率降低(P<0.05),表明氧化损伤模型构建成功。与H2O2+miR-24 NC组比,H2O2+miR-24高表达组上述指标较H2O2+miR-24 NC组升高(P<0.05),促凋亡蛋白Bax和胱天蛋白酶3 mRNA与蛋白表达量增加,抑凋亡蛋白Bcl-2 mRNA和蛋白表达量降低(P<0.05),而H2O2+anti-miR-24组可降低细胞凋亡率、增加细胞存活和迁移率,降低Bax和胱天蛋白酶3 mRNA与蛋白表达水平,增加Bcl-2 mRNA和蛋白表达水平(P<0.05)。结论氧化应激状态下,miR-24可通过上调Bax、胱天蛋白3表达和下调Bcl-2蛋白表达,促进HUVEC凋亡和抑制其存活和迁移能力。