眩痛停方对离体犬基底动脉收缩反应的影响

目的观察眩痛停方对犬离体基底动脉收缩反应的影响。方法分离犬基底动脉并置于血管环灌流装置中,基底动脉预先给予含药血清,记录去氧肾上腺素或高钾离子作用于犬基底动脉后的血管收缩反应。结果眩痛停方对血管平滑肌的张力性收缩具有较好的拮抗作用（与生理盐水组比,P〈0．05）,且随剂量的增加呈现出一定的量效关系;眩痛停方对血管平滑肌的相位性收缩没有抑制作用。结论眩痛停方降低麻醉犬脑血管阻力,增加脑血流量的机制可能与其抑制细胞外钙内流,抑制基底动脉血管收缩有关。     

Vasorelaxant effect of formononetin in the rat thoracic aorta and its mechanisms

The purpose of the present study was to investigate the effect of formononetin and the related mechanisms on isolated rat thoracic aorta. Formononetin concentration dependently relaxed aortic rings precontracted with norepinephrine (NE, 1 μM) or KCl (80 mM). Pretreatment with formononetin noncompetitively inhibited contractile responses of aortas to NE and KCl. The vasorelaxant effect of formononetin partially relied on intact endothelia, which was significantly attenuated by incubation with N^ω-nitro-l-arginine methyl ester (100 μM). In endothelium-denuded rings, glibenclamide (10 μM) and tetraethylammonium (5 mM) showed slight reduction in the vasorelaxant effect of formononetin. Moreover, formononetin reduced NE-induced transient contraction in Ca²⁺-free solution and inhibited the vasocontraction induced by increasing external calcium in medium plus 80 mM KCl. Our results suggested that formononetin induced relaxation in rat aortic rings through an endothelium-dependent manner via nitric oxide synthesis pathway, and also involving an endothelium-independent vasodilatation by the blockade of Ca²⁺ channels. The opening of K⁺ channels might also be one of the mechanisms of formononetin-induced vasorelaxation.     

Mechanism of asynchronous Ca2+ waves underlying agonist-induced contraction in the rat basilar artery

Background and purpose:

Uridine 5''-triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca²⁺ waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced Ca²⁺ waves in VSMCs of the rat basilar artery.

Experimental approach:

Isometric force and intracellular Ca²⁺ ([Ca²⁺]_i) were measured in endothelium-denuded rat basilar artery using wire myography and confocal microscopy respectively.

Key results:

Uridine 5''-triphosphate (0.1–1000 µmol·L⁻¹) concentration-dependently induced tonic contraction (pEC₅₀ = 4.34 ± 0.13), associated with sustained repetitive oscillations in [Ca²⁺]_i propagating along the length of the VSMCs as asynchronized Ca²⁺ waves. Inhibition of Ca²⁺ reuptake in sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca²⁺ waves and resulted in a dramatic drop in tonic contraction. Nifedipine reduced the frequency of Ca²⁺ waves by 40% and tonic contraction by 52%, and the nifedipine-insensitive component was abolished by SKF-96365, an inhibitor of receptor- and store-operated channels, and KB-R7943, an inhibitor of reverse-mode Na⁺/Ca²⁺ exchange. Ongoing Ca²⁺ waves and tonic contraction were also abolished after blockade of inositol-1,4,5-triphosphate-sensitive receptors by 2-aminoethoxydiphenylborate, but not by high concentrations of ryanodine or tetracaine. However, depletion of ryanodine-sensitive SR Ca²⁺ stores prior to UTP stimulation prevented Ca²⁺ waves.

Conclusions and implications:

Uridine 5''-triphosphate-induced Ca²⁺ waves may underlie tonic contraction and appear to be produced by repetitive cycles of regenerative Ca²⁺ release from the SR through inositol-1,4,5-triphosphate-sensitive receptors. Maintenance of Ca²⁺ waves requires SR Ca²⁺ reuptake from Ca²⁺ entry across the plasma membrane via L-type Ca²⁺ channels, receptor- and store-operated channels, and reverse-mode Na⁺/Ca²⁺ exchange.     

法舒地尔联合阿司匹林治疗椎-基底动脉供血不足疗效观察

目的：评价盐酸法舒地尔联合阿司匹林治疗椎-基底动脉供血不足的临床疗效和安全性。方法：选择符合人选标准的58例椎-基底动脉供血不足患者,随机分为观察组30例与对照组28例,所有患者基础治疗相同。观察组应用法舒地尔60mg静脉滴注,每日1次,联合阿司匹林0．1g每日1次口服,对照组应用丹参25ml静脉滴注,每日1次,联合阿司匹林0．1g每131次口服,14d为1个疗程。观察治疗效果及不良反应。结果：治疗2周后,观察组显效率35．6％,总有效率90％,对照组显效率14．0％,总有效率75．0％,两组比较,差异有统计学意义（P〈0．05）．均未观察到明显不良反应。结论：椎-基底动脉供血不足应用法舒地尔联合阿司匹林,可有效改善临床表现,无严重不良反应。     

赛庚啶对大鼠脑血流量及离体家兔基底动脉收缩的影响

赛庚啶对大鼠脑血流量及离体家兔基底动脉收缩的影响鞠敏王美纳刘俊田（西安医科大学药理学教研室，西安７１００６１）赛庚啶（ｃｙｐｒｏｈｅｐｔａｄｉｎｅ，Ｃｙｐ）为一哌啶类抗５－羟色胺及抗组胺药［１］在临床上已应用多年．近年来发现该药具有较强的钙通道阻滞作...     

大鼠脑基底动脉平滑肌细胞培养及功能鉴定

目的探讨大鼠脑基底动脉平滑肌细胞的培养方法,了解生长特性。方法用组织贴块法培养大鼠脑基底动脉平滑肌,用免疫细胞化学法鉴定细胞,用RF-5000荧光分光光度计观察细胞内Ca2+浓度的动态变化来检测其活性。结果培养5d后可见组织块周围有平滑肌细胞长出,2wk后可融合传代,经平滑肌特异性肌动蛋白α-actin鉴定,确定为平滑肌细胞。钙离子通道激动剂可诱导细胞Fura-2荧光比值(F340/F380)上升,细胞活性良好。结论组织贴块法是大鼠脑基底动脉平滑肌细胞培养简单、高效、经济的实验方法,为脑血管疾病发病机制的研究提供了理想的细胞模型。     

尼莫地平对过氧化氢诱导猪脑基底动脉氧化应激损伤的保护作用

目的：探讨尼莫地平对过氧化氢（H2O2）诱导猪脑基底动脉损伤的保护作用。方法：采用去内皮离体血管环灌流的方法，建立H2O2损伤模型。比较正常对照组，H2O2（2×10^-4mol／L）损伤组，维生素C（10^-4mol／L）组，尼莫地平高、中、低剂量（5×10^-6、5×10^-7、5×10^-8mol／L）组血管环对KCl、苯肾上腺素的张力；检测各组血管组织匀浆中的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH—PX）活性及丙二醛（MDA）含量。结果：（1）H2O2损伤组与正常对照组比较，血管环对KCl、苯肾上腺素的收缩反应明显增加；尼莫地平高、中、低剂量组呈剂量依赖性抑制KCl、苯肾上腺素对血管环的收缩反应。（2）H2O2损伤组MDA含量升高，SOD、CAT、GSH—PX活性降低，与正常对照组比较，差异有统计学意义（P〈0．05）。尼莫地平高、中、低剂量均能降低组织中MDA含量，增强SOD、CAT、GSH-PX，的活性，与H2O2损伤组比较，差异有统计学意义（P〈0．05）。结论：钙通道阻断剂尼莫地平具有抗氧化应激作用，能预防H2O2对脑基底动脉血管的氧化损伤。     

基底动脉尖综合征63例临床分析

目的 探讨基底动脉尖综合征（TOBS）的临床及影像学特征。方法 对63例TOBS患者的临床表现及影像学资料进行回顾性分析。结果 栓塞和血栓形成是TOBS的主要病因，眩晕、意识障碍、眼球运动障碍、瞳孔异常、偏盲等是该病最常见的临床表现，以丘脑或中脑为核心合并其他部位梗塞是该病影像学重要特征。结论TOBS同时具有幕上及幕下多处梗塞，并发症多，预后差，早期行MRI检查可明确诊断，全面综合治疗可改善预后。     

双苯氟嗪、氟桂利嗪、桂利嗪对5-羟色胺所致离体猪基底动脉收缩的拮抗作用(英文)

目的:探索双苯氟嗪(Dip,一种我国自行合成的桂利嗪衍生物),对5-羟色胺所致的脑动脉收缩的影响。方法:比较双苯氟嗪、氟桂利嗪(Flu)、桂利嗪(Cin)对5-羟色胺所致离体猪基底动脉收缩的抑制及两种收缩成分的影响。结果:三者的拮抗作用强度顺序(IC_(50))为Dip 4.0μmol·L~(-1)>Flu15.6μmol·L~(-1)>Cin 25.2umo·L~(-1)。这三种药对5-羟色胺所致离体猪基底动脉的两种收缩成分均有拮抗。Dip和Cin抑制收缩的快速相强于持续相,而Flu对二者的作用无显著差异。结论:在Dip,Flu和Cin三种药之中,Dip对脑血管的扩张作用最强,其原因主要与抑制内钙的释放有关。     

卡托普利对电解灌流液所致兔离体脑基底动脉痉挛的保护作用

１０ｍＡ直流电电解Ｋｒｅｂｓ液１ｍｉｎ引起兔基底动脉收缩，灌注压明显增高，血管壁组织丙二醛含量升高及兔胸主动脉，脑基底动脉内皮舒张因子（ＥＤＲＦ）释放量明显减少，卡托普利（Ｃａｐ）２５，５０，１００ｕｍｏｌ·Ｌ￣（－１）可浓度依赖性地抑制电解产生自由基诱发脑血管收缩作用，Ｃａｐ１００ｐｍｏｌ·Ｌ￣（－１）与吲哚美辛合用可完全取消Ｃａｐ的作用，此外Ｃａｐ１００ｕｍｏｌ·Ｌ￣（－１）还具有明显抑制血管壁丙二醛生成及保护内皮细胞释放ＥＤＲＦ的作用，提示Ｃａｐ对外源性氧自由基损伤脑血管保护作用可能由前列环素和ＥＤＲＰ共同中介。     

Cysteinyl leukotrienes and leukotriene B mediate vasoconstriction to arginine vasopressin in rat basilar artery

Arginine vasopressin (AVP) has been reported to be involved in the development of cerebral vasospasm after haemorrhage and cerebral oedema following ischaemia. Endogenously produced 5-lipoxygenase metabolites are able to contract isolated endothelium-preserved arterial strips and modulate vascular permeability. The present study addresses the role of 5-lipoxygenase and its products, namely cysteinyl leukotrienes (CysLTs) and leukotriene (LT) B4, in the contraction induced by AVP in rat basilar artery. Contractile responses to LTD4, LTC4, LTB4 or AVP were assessed in spiral preparations of rat endothelium-intact basilar artery. Contractions to AVP were determined in the absence or presence of 5-lipoxygenase inhibitors or CysLT1 or BLT receptor antagonists. Contractile responses to leukotrienes and AVP are expressed as a percentage of the contraction induced by 80 mmol/L KCl. Leukotriene D4, LTC4 and LTB4 acted as vasoconstrictor agents in rat basilar artery, causing contractions (all at concentrations of 1 micromol/L) of 42 +/- 13, 54 +/- 15 and 25 +/- 6% of the response to 80 mmol/L KCl, respectively. A concentration-response curve was constructed for AVP over the range 1 pmol/L to 10 nmol/L and an EC50 value of 0.19 +/- 0.02 nmol/L (n = 30) was determined. The presence of the 5-lipoxygenase inhibitors ZM 230487 (10 nmol/L and 0.1 and 1 micromol/L) and AA 861 (1, 3, 10, and 30 micromol/L), the CysLT1 receptor antagonist MK 571 (3, 10 and 30 micromol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30 micromol/L for both) in the organ bath significantly attenuated the contractions induced by AVP in rat basilar artery (P < 0.05). The experimental results of the present study provide the first evidence for the involvement of CysLTs and LTB4 in the in vitro constriction induced by AVP in rat basilar artery. In the context of previously reported involvement of AVP in the development of cerebral vasospasm and oedema, the present study draws attention to the potential role played by the 5-lipoxygenase pathway in these pathological processes.     

Cholinergic prejunctional inhibition of nitrergic neurotransmission in the guinea-pig isolated basilar artery

1. The effects of endogenous and exogenous acetylcholine (ACh) on nitrergic relaxations elicited by electrical field stimulation (EFS) were studied in guinea-pig endothelium-denuded basilar artery preparations precontracted with 1 mumol/L prostaglandin F2 alpha and a possible role of K+ channels in mediating the effects was investigated. 2. Acetylcholine (3 mmol/L) and physostigmine (10 mumol/L) produced small, yet statistically significant, inhibitions of EFS-induced nitrergic relaxations, while atropine (1 mumol/L) slightly enhanced the nitrergic response. The ACh-induced inhibition was atropine sensitive. Acetylcholine or atropine did not affect relaxations induced by sodium nitroprusside. 3. The inhibition of nitrergic relaxations by 3 mumol/L ACh was prevented by the K+ channel blockers tetraethylammonium and 4-aminopyridine, but was not changed by iberiotoxin, apamin or glibenclamide. 4. Neither vasoactive intestinal polypeptide nor the alpha 2-adrenoceptor agonists noradrenaline and clonidine modulated nitrergic neurotransmission in the guinea-pig basilar artery. 5. The findings show that ACh acts on prejunctional muscarinic receptors of nitrergic nerves to inhibit nitrergic neurotransmission. It is suggested that endogenous ACh may have this effect; however, the physiological significance of this prejunctional modulation is not clear due to the relatively small effect produced. The prejunctional inhibitory action of ACh may involve opening of neuronal K+ channels.     

倍他司汀联合氟桂利嗪治疗椎基底动脉供血不足的临床研究

目的：观察倍他司汀联合氟桂利嗪治疗椎基底动脉供血不足的疗效。方法：将所有病例随机分为氟桂利嗪组和联合治疗组。氟桂利嗪组给予氟桂利嗪胶囊治疗;联合治疗组在此基础上给予倍他司汀口服治疗。治疗后使用经颅多普勒血流诊断系统（TCD）检测血流情况,观察两组治疗效果。结果：联合治疗组的有效率高于氟桂利嗪组,P＜0.05。两组经过治疗,血流异常情况得到改善,联合治疗组血流异常情况的改善情况要优于氟桂利嗪组,P＜0.05。结论：倍他司汀联合氟桂利嗪治疗椎基底动脉供血不足安全有效。     

槲皮素和山柰酚对痤疮相关致病菌抗菌作用及网络药理学研究

目的通过体外实验探究槲皮素和山柰酚对痤疮相关致病菌的抗菌作用,运用网络药理学和分子对接技术预测二者治疗痤疮的作用机制。方法 2022年 1月至 2022年 6月通过体外实验测定抑菌环直径、最小抑菌浓度( MIC)和最小杀菌浓度(MBC)、药物时间抑菌曲线评判槲皮素和山柰酚的抗菌活性;检索 DrugBank、HERB及 BATMAN-TCM数据库收集槲皮素和山柰酚作用靶点,检索 GeneCards、OMIM、DisGeNET、DrugBank数据库获得痤疮靶点;取两靶点集交集,通过 STRING数据库获得蛋白互作网络, CytoHubba拓扑分析得到核心靶点, Metascape数据库进行基因本体( GO)和京都基因与基因组百科全书(KEGG)通路富集分析, AutoDock软件进行活性成分与核心靶点的分子对接验证。结果槲皮素和山柰酚对三种痤疮相关致病菌均有较好抗菌活性;槲皮素对三种菌的 MIC≤78.13 mg/L,MBC≤156.25 mg/L;山柰酚对金黄色葡萄球菌和表皮葡萄球菌的 MIC≤39.06 mg/L,MBC≤78.13 mg/L,对痤疮丙酸杆菌的 MIC≤78.13 mg/L,MBC≤156.25 mg/L。通过网络药理学筛选出 AP-1转录因子亚基( JUN)、转录因子 p65(RELA)、肿瘤坏死因子(TNF)、白细胞介素(IL)-6等 8个核心靶点; KEGG富集分析示 IL-17信号通路、 TNF信号通路等 7条信号通路发挥关键作用;将两种化合物与 JUN、RELA、TNF、IL-6进行对接,结合自由能均小于 ?20.92 kJ/mol,表明化合物与核心靶点蛋白形成稳定构象。结论槲皮素和山柰酚对三种痤疮致病菌均有抗菌活性;网络药理学研究显示两种中药成分治疗痤疮具有多靶点、多通路协同特点,具有进一步开发和研究的价值。     

新结构Rho激酶抑制剂对离体胸主动脉血管环舒张作用及机制研究

目的评价2个全新结构小分子Rho激酶抑制剂J35242和J35243对离体大鼠胸主动脉血管环的舒张作用,并探讨其作用机制。方法利用离体大鼠胸主动脉血管环模型,分别用高浓度KCl和去甲肾上腺素(norepinephrine,NE)预刺激,评价化合物的舒张血管活性;通过各种工具药干预,观察化合物舒张血管作用的内皮相关机制、钾通道相关机制和钙离子相关机制。结果 J35242和J35243可以剂量依赖性舒张高浓度KCl和NE预收缩的血管环,并呈现一定的内皮依赖性;L-NAME和亚甲蓝可在一定程度上影响其舒张作用;化合物还明显抑制由细胞内钙释放和外钙内流引起的血管收缩,说明其可能通过阻断钙离子通道发挥舒张血管作用;另外两个化合物可能不是通过开放钾离子通道发挥舒张血管作用。结论 J35242和J35243在体外具有一定的舒张血管作用,并且J35242的作用要强于J35243,其机制可能依赖于血管内皮功能,另外可能与抑制平滑肌细胞钙离子通道,降低细胞内钙离子浓度相关。     

槲皮素及其水溶性衍生物体外抑菌试验

目的初步探究槲皮素及其水溶性衍生物槲皮素-7-硫酸酯钠、槲皮素-7,4-二硫酸酯二钠的体外抑菌效果。方法以革兰阳性菌：金黄色葡萄球菌,革兰阴性菌：大肠埃希菌、痢疾志贺菌、铜绿假单胞菌为实验菌株,分别采用MH琼脂稀释法和药敏纸片法测定槲皮素及其水溶性衍生物的最小抑菌浓度。结果琼脂稀释法,槲皮素及其水溶性衍生物槲皮素-7-硫酸酯钠和槲皮素-7,4-二硫酸酯二钠梯度浓度0.5～0.0004875mg/mL范围内各种细菌均有生长;药敏纸片法,槲皮素及其水溶性衍生物槲皮素-7-硫酸酯钠和槲皮素-7,4-二硫酸酯二钠对各种细菌无明显抑菌作用。结论槲皮素、槲皮素-7-硫酸酯钠和槲皮素-7,4-二硫酸酯二钠对上述四种细菌均无明显抑菌作用。     

槲皮素对四氯化碳致大鼠肝纤维化的缓解作用及其机制研究（英文）

槲皮素是一种广泛存在于蔬菜和水果中的酚类植物化学物质,具有抗氧化、抗炎、抗病毒和免疫调节活性,已成功应用于急慢性疾病的治疗。本研究目的是探讨槲皮素对大鼠肝纤维化的缓解作用并探讨其作用机制。将健康雄性SD大鼠随机分为正常组、模型组和槲皮素组,每组6只。通过腹腔注射1 m L/kg四氯化碳(50%v/v,溶于橄榄油),每周2次,持续6周诱导肝脏纤维化,并于第7周灌胃给予槲皮素(100mg/kg/d)持续至第12周结束。末次给药1h后,收集血液和肝脏样品。利用全自动生化仪检测血清肝功能参数(AST、ALT、ALP、GGT和TBA);HE、Masson和天狼星红染色观察肝组织病理形态;Westernblotting评价肝纤维化因子(TGF-β1、α-SMA、MMP2和MMP9)和胆汁酸相关调节蛋白(FXR、CYP7A1、CYP8B1和CYP27A1)的表达;采用试剂盒检测肝组织氧化应激标志物(GSH、GSH-Px、GR、SOD和MDA)的含量;运用LC-MS/MS测定肝组织中胆汁酸含量。结果发现与模型组相比,给予槲皮素治疗后可显著降低血清AST、ALT和TBA含量(P <0.05);肝纤...     

Vasodilation activity of dipfluzine metabolites in isolated rat basilar arteries and their underlying mechanisms

Identifying the metabolites of a drug has become an indispensable task in the development of new drugs. Dipfluzine (Dip) is a promising candidate for the treatment of cerebral vascular diseases and has 5 metabolites (M1∼M5) in rat urine and liver microsomes, but their biological activity is still unknown. Because selective cerebral vasodilation is a main role of Dip, we investigated the vasodilation of Dip and its 5 metabolites in isolated Sprague-Dawley (SD) male rat basilar arteries preconstricted with high-K⁺ or 5-HT. The results showed that only M1 possessed concentration-dependent inhibitory activity on the vasoconstriction of arteries with or without the endothelium, and M1 has a more potent vasodilatory effect than Dip on both contraction models. Like Dip, the vasodilatory mechanisms of M1 may be not only related to receptor-operated and voltage-dependent calcium ion channels of smooth muscle cells but also to the release of NO and EDHF from endothelial cells and the opening of Ca²⁺-activated K⁺ channels and ATP-sensitive potassium ion channels. Unlike Dip, the vasodilation mechanism of M1 is also related to the opening of voltage-sensitive K⁺ channel. Together with more selectivity to non-VDCC than Dip, this may partially explain why M1 has stronger vasodilatory effects than Dip. The mechanisms of vasodilation of Dip and M1 may result from the combined action of these or other factors, especially blocking non-endothelium dependent non-VDCC and endothelium dependent IK_Ca channels. These results point to the possibility that M1 provides synergism for the clinical use of Dip, which may inform the synthesis of new drugs.     

槲皮素对心肌缺血再灌注损伤的保护作用及机制研究

目的探讨槲皮素(QU)对心肌缺血再灌注(MI/R)损伤的保护作用及其作用机制。方法采用结扎左冠脉前降支30 min再灌注2 h的方法复制MI/R损伤大鼠模型,随机分为假手术组、模型组、QU组(25、50、100 mg/kg),每组10只,各组于术前1周开始灌胃给药,1次/d。再灌注后取心脏,染色法测定心肌梗死面积;免疫组化法测定心肌组织NF-κB和ICAM-1表达情况;取心肌匀浆,髓过氧化物酶(MPO)法测定中性粒细胞浸润情况。结果QU高、中剂量可分别缩小心肌梗死面积至25.00%、25.31%,与模型组(32.55%)比较差异有统计学意义(P<0.05);QU各剂量组心肌MPO活力分别降低至185.70、190.66、210.03 U/g,与模型组(311.72 U/g)比较差异均有统计学意义(P<0.05,P<0.01);QU各剂量组心肌组织ICAM-1阳性区面积百分比分别降至32.08%、32.65%、36.42%,与模型组(42.67%)比较差异有统计学意义(P<0.05,P<0.01);QU高、中剂量可使心肌NF-κB的表达水平分别降低至55.23%、54.90%,与模型组(61.05%)比较差异有统计学意义(P<0.05)。结论QU预处理可保护MI/R所致心肌损伤,其机制与抑制中性粒细胞浸润、下调NF-κB和ICAM-1的表达等有关。