维拉帕米与1—荷包牡丹碱合用对体外KB细胞增殖的影响

低剂量１－荷包牡丹碱和无毒剂量的维拉帕米合用对细胞增殖的抑制作用经单用１－荷包牡丹碱时增强，其半抑制浓度ＩＣ５０下降到单独应用１－荷包牡丹碱的１／８。联合用药后的细胞集落形成单独用１－荷包牡丹下降１／３－２０。结果提示维拉帕米能增强荷包碱对体外ＫＢ细胞的抗癌活性。     

维拉帕米与1－荷包牡丹碱合用对体外KB细胞增殖的影响

低剂量１－荷包牡丹碱和无毒剂量的维拉帕米合用对细胞增殖的抑制作用比单用１－荷包牡丹碱时增强，其半抑制浓度ＩＣ５０值下降到单独应用１－荷包牡丹碱的１／８。联合用药后的细胞集落形成率比单独用１－荷包牡丹碱下降１／３～２０。结果提示维拉帕米能增强荷包牡丹碱对体外ＫＢ细胞的抗癌活性。     

AP-V和荷包牡丹碱对急性低压性低氧大鼠下丘脑内生长抑素阳性神经元的影响(英文)

目的:研究2-Amino-5-phosphonovalerate-pharmacology(AP-V)和荷包牡丹碱对急性低压性低氧大鼠下丘脑内生长抑素(SST)阳性神经元的影响。方法:用免疫组织化学和原位杂交技术检测大鼠下丘脑内SST-IR和SS mRNA阳性神经元数。结果:急性低氧引起下丘脑室周核(PeV)、室旁核(PVN)、弓状核(ARC)SST-IR和SS mRNA阳性神经元数明显增多,该效应可被NMDA受体拮抗剂AP-V(10μg,icv)明显抑制;而GABA_A受体拮抗剂荷包牡丹碱(1.5mg·kg~(-1),ip)则使其增强。结论:这些结果表明下丘脑内的生长抑素参与了急性低压低氧反应,且谷氨酸和GABA分别通过NMDA受体与GABA_A受体影响下丘脑内生长抑素的释放与合成。     

莲心碱对离体猪冠状动脉条收缩性能的影响

目的：观察莲心碱（Lien）拮抗氯化钾（KCl），乙酰胆碱（Ach）和组铵（Hist）所致猪冠状动脉条收缩的作用。方法：离体平滑肌实验方法。结果：不同剂量莲心碱对Kcl,Ach,Hist量效曲线均呈非竞争性拮抗作用，pD'2值分别为4．78，3．85和4．25。莲心碱和维拉帕米（Ver）均能抑制组胺诱导的依内钙收缩，而对氯化钙诱导的依外钙收缩作用较弱。结论：莲心碱具有扩张冠脉的作用，且对冠脉平滑肌细胞依内钙性收缩及依外钙性收缩均有抑制作用。     

荷包牡丹碱对人肺癌A549细胞生长及端粒酶活性的抑制作用

目的探讨荷包牡丹碱对人肺癌A549细胞生长的抑制作用及其作用机制。方法 A549细胞加入荷包牡丹碱0～200μmol.L-1分别作用24,48和72 h,MTT法测定A549细胞的生长抑制作用。荷包牡丹碱0～20μmol.L-1作用72 h,端粒重复序列扩增(TRAP)法测定端粒酶活性。变温紫外法检测荷包牡丹碱9μmol.L-1对端粒酶G-四链体的稳定作用。结果荷包牡丹碱25,50,100和200μmol.L-1作用细胞72 h后的抑制率分别为33.4%,88.2%,88.6%和89.4%,明显高于正常对照组细胞(P<0.05),并具有量效(r=0.906,P<0.05)和时效(r=0.949,P<0.05)性。与正常对照组相比,荷包牡丹碱5,10,15和25μmol.L-1可有效抑制A549细胞端粒酶的活性(P<0.05),相对TRAP端粒酶活性从正常对照组的1.471±0.102分别降低为1.093±0.054,1.013±0.016,0.554±0.034,0.365±0.081(P<0.05)。荷包牡丹碱9μmol.L-1使G-四链体的熔点值从正常对照组的48℃提高到54℃。结论荷包牡丹碱可以通过稳定G-四链体结构,抑制端粒酶活性,有效抑制人肺腺癌细胞A549的生长。     

鞘内及侧脑室注射NMDA、荷包牡丹碱对异氟烷肌松作用的影响

目的探讨异氟烷的肌肉松弛作用机制及与N-甲基-D-天冬氨酸(NMDA)、γ-氨基丁酸A(GABAA)受体的关系。方法小鼠腹腔注射异氟烷,2 min后在鞘内或侧脑室注射不同剂量的NMDA或荷包牡丹碱(Bic)。用YLS-13A大小鼠抓力测定仪测定各组给药前后不同时间点的抓力。结果鞘内注射102、0 ng的NMDA或鞘内注射不同剂量的Bic及侧脑室注射0.2μg的Bic均能部分拮抗异氟烷所致肌松作用(P<0.01或P<0.05)。结论异氟烷主要作用于脊髓产生肌松作用,NMDA及GABAA受体可能是异氟烷产生肌松作用的靶点之一。     

侧脑室注射蝇蕈醇和荷包牡丹碱对大鼠异氟烷最低麻醉浓度的影响

大鼠侧脑室置管后2 d, 观察icv GABA_A受体激动剂蝇蕈醇和(或)其拮抗剂荷包牡丹碱对麻醉箱内异氟烷最低有效浓度（反映最低肺泡有效浓度）和翻正反射恢复时间的影响. 结果表明icv 5 mmol·L^-1蝇蕈醇2 μL明显降低箱内异氟烷最低麻醉浓度, 延长大鼠翻正反射恢复时间; icv 0.5 mmol·L^-1荷包牡丹碱2 μL对异氟烷的最低麻醉浓度和翻正反射恢复时间皆无影响, 但可部分拮抗蝇蕈醇降低异氟烷最低麻醉浓度和延长翻正反射恢复时间的作用. 以上实验结果提示, 蝇蕈醇和异氟烷间有协同作用, 但脑内的GABAA受体可能不是异氟烷全麻作用的主要靶位.     

Effects of taurine on contractions of the porcine coronary artery

The actions and mechanisms of taurine on vascular contractions have been studied in the isolated porcine coronary artery. Taurine depressed histamine-, serotonin-, KCl- and CaCl₂-induced contractions in a concentration-dependent manner, with maximal contractions being depressed by 43.4%, 46.2%, 33.3% and 43.3%, respectively. Taurine relaxed arterial rings that were precontracted by either 30 mM KCl or 0.3 μMU46619, a thromboxane A₂ analog, in a concentration-dependent manner, and the maximal relaxations were 39.4% and 38.7%, respectively. The vasorelaxations were nearly abolished by pretreatment with either the inward rectifier K⁺ channel (K_IR) inhibitor, BaCl₂ or the ATP sensitive K⁺ channel (K_ATP) inhibitor, glibenclamide, and were attenuated by the Ca²⁺-activated K⁺ channel (K_Ca) inhibitor tetraethylammonium. Denudation of the endothelium, and treatment with the nitric oxide synthase inhibitor, L-NAME, the cyclooxygenase inhibitor, indomethacin, or the voltage gated K⁺ channel (K_V) inhibitor 4-aminopyridine did not affect the relaxation. The present results show that taurine antagonizes and relaxes the contractions of the porcine coronary artery, and suggest that the activation of K_IR,K_ATP and K_ca may be involved in taurine-induced relaxation of the porcine coronary artery.     

Nicorandil stimulates release of adenyl purines from porcine coronary artery

1. To clarify the mechanism of the cardioprotective effect of nicorandil (2-nicotinamidoethyl-nitrate ester), the effects of nicorandil and nitric oxide (NO) donors on the release of ATP, ADP, AMP and adenosine from arterial segments and cultured endothelial cells of the porcine coronary artery were examined. 2. Nicorandil significantly increased the release of total adenyl purines from arterial segments and from cultured endothelial cells. 3. Cromakalim, an ATP-sensitive K+ channel opener, did not affect the release of total adenyl purines from coronary artery segments. 4. s-Nitroso-N-acetyl-D,L-penicillamine and isosorbide dinitrate, NO donors, significantly increased the release of total adenyl purines from coronary artery segments. 5. These results demonstrate that nicorandil stimulates ATP release from the coronary artery by acting not as an ATP-sensitive K+ channel opener, but as a nitrate, thus suggesting the cardioprotective properties of nicorandil.     

二乙酰基莲心碱对猪冠状动脉条的影响

目的:观察二乙酰基莲心碱拮抗氯化钾、乙酰胆碱(Ach)和组胺(His)所致猪冠状动脉条收缩的作用.方法:离体平滑肌实验方法,观察二乙酰基莲心碱对氯化钾,Ach,His所致猪冠状动脉条收缩曲线的影响以及在无钙克氏液中,对His引起猪冠状动脉条第一相收缩和钙引起第二相收缩的影响.结果:不同剂量二乙酰基莲心碱可使氯化钾,Ach,His所致冠脉条收缩量效曲线呈非竞争性拮抗作用,对冠脉条第一相和第二相收缩都有明显的抑制作用结论:二乙酰基莲心碱具有扩张冠脉的作用,此作用与拮抗细胞内钙的释放和抑制外钙内流有关.     

冠脉壁上阿片及苯环利定受体的自显影观察

为了了解冠状动脉上苯环利定（Ｐｈｅｎｃｙ－ｃｌｉｄｉｎｅ，Ｐｈｅ）受体及阿片受体的分布，利用猪冠状动脉的大、小支作了离体血管放射自显影研究，显微镜下观察到，猪冠脉壁上有与［３Ｈ］Ｐｈｅ和［３Ｈ］Ｅｔｏｒ－ｐｈｉｎｅ特异结合位点，它们均主要分布于冠脉的外膜上。通过［３Ｈ］Ｏｈｍｅｆｅｎｔａｎｙｌ自显影观察，冠脉上未见特异结合颗粒，提示冠脉上的阿片受体不是μ型。     

Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery

Summary The pharmacological properties of the endothelial 5-hydroxytryptamine (5-HT) receptors involved in relaxation of vascular smooth muscle were determined in rings of pig coronary artery contracted with 10 nmol/1 of the thromboxane A₂ receptor agonist 9,11-dideoxy-11,9-epoxy-methano-prostaglandin F₂ (U 46619).(1) In the presence of 10 mol/l ketanserin, relaxation was obtained with: 5-HT (apparent pD₂ value 7.00), 5-carboxamidotryptamine (5-CONH₂-T; 6.42), 5-aminotryptamine (5-NH₂-T; 5.96), 5-methoxytryptamine (5-OCH₃-T; 5.92), tryptamine, 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline maleate (CGS 12066 A) and 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969). The maximum relaxation obtainable with the agonists was about 40–60% of the U 46619-induced contraction and the concentration-response curves for 5-HT, 5-NH₂-T and 5-OCH₃-T were bell-shaped. The endothelium-dependence of this effect (i. e. the failure to relax the artery in endothelium-denuded preparations) was demonstrated for 5-HT, 5-CONH₂-T, RU 24969, CGS 12066A and tryptamine.(2) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 4-hydroxytryptamine, quipazine and yohimbine were ineffective in decreasing the tension of arteries with or without endothelium. Ipsapirone elicited full relaxation of U 46619-induced contraction, but this effect was not endothelium-dependent.(3) Metitepine (0.03-1 mol/l), 6-chloro-2-(1-piperazinyl)pyrazine (MK 212; 10 mol/l), methysergide (1 gmol/l) and cyanopindolol (0.1 mol/l) antagonized the relaxing effect of 5-HT in a non-surmountable manner, whereas metergoline (0.1 mol/l), quipazine (10 mol/l), yohimbine (1 mol/l), propranolol (1 mol/l) and (3-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930; 0.1 mol/l) did not. However, spiroxatrine (0.1 mol/l) and mesulergine (10 mol/l) enhanced the 5-HT-induced relaxation. The endothelium-dependent relaxation induced by 5-CONH₂-T was also inhibited by metitepine 1 gmol/l.(4) The 5-HT-induced relaxation was probably mediated by release of an endothelium-derived relaxing factor (EDRF). Gossypol, an inhibitor of EDRF, virtually abolished the 5-HT-induced relaxation while indometacin, an inhibitor of cyclooxygenase and accordingly of PGI₂ formation, did not.In conclusion, the failure of ketanserin and ICS 205–930 to counteract the relaxant effect of 5-HT receptor agonists excludes the involvement of 5-HT₂ and 5-HT₃ receptors, respectively, in the endothelium-dependent relaxation of the porcine coronary artery. The rather high potency of 5-CONH₂-T and the ability of certain 5-HT receptor antagonists, such as metitepine, methysergide and cyanopindolol, to counteract the effect of 5-HT are compatible with a 5-HT₁ character of the endothelial receptor. However, on the basis of the present data, no final classification, in particular with respect to the known 5-HT₁ receptor subtypes, is possible. Classification is also hampered by the bell-shaped character of the concentration-response curves for 5-HT receptor agonists and by their property to produce only partial relaxation. Send offprint requests to M. Gothert at the above address     

胃网膜右动脉在猪全动脉化冠状动脉搭桥中的实验研究

目的 评价胃网膜右动脉(RGEA)在冠脉旁路移植术中可行性。方法选取实验用猪80例,随机分为实验组(40例)和对照组(40例),两组均行心脏不停跳搭桥术,实验组采用乳内动脉-前降支、RGEA-后降支的方式搭桥,对照组采用乳内动脉-前降支、大隐静脉-后降支的方式搭桥。记录并比较两组手术时间、术中出血量,桥血管流量和搏动指数、术后24小时内心包纵隔引流管引流量和术后总机械通气时间。结果 实验组的手术时间和术后总机械通气时间较对照组增加(P<0.01),实验组与对照组的术中出血量,桥血管流量和搏动指数、术后24小时内心包纵隔引流管引流量与对照组无显著差异(P>0.05)。结论 胃网膜右动脉是可供选择的动脉移植物之一,在冠脉外科有良好的可行性和应用前景。     

经桡动脉和股动脉途径介入治疗复杂冠状动脉病变的临床疗效分析

目的探讨不同介入途径治疗复杂冠状动脉病变的临床疗效和可行性。方法选取614例有复杂冠状动脉病变冠心病患者,其中经桡动脉途径患者304例（桡动脉组）,股动脉途径患者310例（股动脉组）,观察介入手术成功率、卧床时间、术后发生并发症等情况。结果 2组患者在年龄、性别、危险因素等方面比较,差异均无统计学意义（P〉0.05）;桡动脉组手术成功率为97.7%,股动脉组为98.1%,2组成功率差异无统计学意义（P〉0.05）;桡动脉组术后并发症发生率明显低于股动脉组（P〈0.05）;卧床时间明显短于股动脉组（P〈0.05）;平均住院时间及住院期间主要心血管事件发生率差异无统计学意义（P〉0.05）。结论经桡动脉途径介入治疗冠状动脉复杂病变成功率高,且术后并发症发生率低,不增加心血管事件。     

杂交冠状动脉血运重建术与CABG治疗多支冠状动脉疾病中远期随访的Meta分析

目的 系统评价杂交冠状动脉血运重建术（HCR）与冠状动脉旁路移植术（CABG）治疗多支冠状动脉疾病 中远期疗效与并发症。方法 系统检索Embase、PubMed、Web of Science、Cochrane Central Registry of Controlled Trials （Central）、万方数据、中国知网,筛选符合纳入标准的文献,并计算每项研究中的比值比（odds ratio,OR）和95%置信 区间（95%CI）,采用RevMan 5.3软件进行Meta分析。结果 9篇文献纳入研究,累计研究对象4 030例,其中1 142例 接受HCR治疗,2 888例接受传统CABG治疗。Meta分析结果显示：（1）中远期随访中HCR组术后全因病死率（OR= 0.72,95%CI：0.54～0.96）和主要心脑血管事件（MACCE,OR=0.54,95%CI：0.35～0.82）均低于CABG组。而在血运重 建（OR=0.90,95%CI：0.61～1.34）及心肌梗死或心绞痛发生率（OR=0.51,95%CI：0.18～1.41）方面差异无统计学意义。 （2）中期随访中 HCR 组的 MACCE 发生率低于 CABG 组（OR=0.31,95%CI：0.15～0.66）,而全因病死率（OR=0.79, 95%CI：0.52～1.22）、血运重建（OR=0.77,95%CI：0.30～1.96）以及心肌梗死或心绞痛发生率（OR=0.71,95%CI：0.05～ 9.46）等差异无统计学意义。（3）远期随访中HCR组术后全因病死率（OR=0.67,95%CI：0.46～0.98）及心肌梗死或心绞 痛发生率（OR=0.32,95%CI：0.15～0.68）均低于 CABG 组。而在 MACCE（OR=0.72,95%CI：0.43～1.21）与血运重建 （OR=0.93,95%CI：0.60～1.45）方面差异无统计学意义。结论 HCR相比CABG可降低多支冠状动脉病变患者的中 期MACCE和远期全因病死率、心肌梗死或心绞痛发生率。     

Quercetin and its principal metabolites, but not myricetin, oppose lipopolysaccharide-induced hyporesponsiveness of the porcine isolated coronary artery

BACKGROUND AND PURPOSE

Quercetin is anti-inflammatory in macrophages by inhibiting lipopolysaccharide (LPS)-mediated increases in cytokine and nitric oxide production but there is little information regarding the corresponding effect on the vasculature. We have examined the effect of quercetin, and its principal human metabolites, on inflammatory changes in the porcine isolated coronary artery.

EXPERIMENTAL APPROACH

Porcine coronary artery segments were incubated overnight at 37°C in modified Krebs-Henseleit solution with or without 1 µg·mL⁻¹ LPS. Some segments were also co-incubated with quercetin-related flavonoids or Bay 11-7082, an inhibitor of NFκB. Changes in isometric tension of segments to vasoconstrictor and vasodilator agents were recorded. Nitrite content of the incubation solution was estimated using the Griess reaction, while inducible nitric oxide synthase was identified immunohistochemically.

KEY RESULTS

Lipopolysaccharide reduced, by 35–50%, maximal contractions to KCl and U46619, thromboxane A₂ receptor agonist, and impaired endothelium-dependent relaxations to substance P. Nitrite content of the incubation medium increased 3- to 10-fold following exposure to LPS and inducible nitric oxide synthase was detected in the adventitia. Quercetin (0.1–10 µM) opposed LPS-induced changes in vascular responses, nitrite production and expression of inducible nitric oxide synthase. Similarly, 10 µM Bay 11-7082, 10 µM quercetin 3′-sulphate and 10 µM quercetin 3-glucuronide prevented LPS-induced changes, while myricetin (10 µM) was inactive. Myricetin (10 µM) prevented quercetin-induced modulation of LPS-mediated nitrite production.

CONCLUSION AND IMPLICATIONS

Quercetin, quercetin 3′-suphate and quercetin 3-glucuronide, exerted anti-inflammatory effects on the vasculature, possibly through a mechanism involving inhibition of NFκB. Myricetin-induced antagonism of the effect of anti-inflammatory action of quercetin merits further investigation.