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1.
Stroke is an acute cerebrovascular disease caused by ruptured or blocked blood vessels.For the prevention of ischemic stroke,the coagulation state of blood and cerebrovascular protection should be considered.Our previous study has shown that salvianolic acid A(SAA),which is a water-soluble component from the root of Salvia Miltiorrhiza Bge,prevents thrombosis with a mild inhibitory effect on platelet aggregation.In this study we investigated the preventive effects of SAA on cerebrovascular endothelial injury caused by ischemia in vivo and oxygen-glucose deprivation(OGD)in vitro,and explored the underlying mechanisms.An autologous thrombus stroke model was established in SD rats by electrocoagulation.SAA(10 mg/kg)was orally administered twice a day for 5 days before the operation.The rats were sacrificed at 24 h after the operation.We showed that pretreatment with SAA significantly improved the neurological deficits,intracerebral hemorrhage,BBB disruption,and vascular endothelial dysfunction as compared with model group.In human brain microvascular endothelial cells(HBMECs),pretreatment with SAA(10μM)significantly inhibited OGD-induced cell viability reduction and degradation of tight junction proteins(ZO-1,occludin,claudin-5).Furthermore,we found that SAA inhibited the upregulation of Src signaling pathway in vivo and vitro and reversed the increased expression of matrix metalloproteinases(MMPs)after ischemic stroke.In conclusion,our results suggest that SAA protects cerebrovascular endothelial cells against ischemia and OGD injury via suppressing Src signaling pathway.These findings show that pretreatment with SAA is a potential therapeutic strategy for the prevention of ischemic stroke.  相似文献   

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3.
The effects and safety of ticlopidine in the prevention of ischernic cerebral stroke were studied and compared with those of low-dose aspirin.Patients (n=329) with TIA or mild ischemic cerebral stroke were randomly assigned to ticlopidine group (165 cases) or aspirin group (164 cases). These patients were randomly allocated to receive either ficlopidine 250 mg or aspirin 50 mg daily and did not take any other platelet antiaggregating  相似文献   

4.
Objective To determine the antiplatelet and antithrombotic efficacies of MV1 serine protease on coronary arterial thrombosis in a canine model of unstable angina.Methods Pentobarbital-anesthetized Beagles(total of 30)were used in which acute damage of the proximal left circumflex coronary artery,together with mechanical stenosis,produced the phenomenon of cyclic flow reduction(CFR)in the Folts model of unstable angina.When the platelet plug was removed by rubbing the vessel,the occlusion returned reproducibly for at least 3 hours in control studies.To evaluate the antithrombotic efficacy of MV1,CFR was first established over a period of one hour,thereafter,MV1(0.3,0.6 mg·kg-1 i.v.bolus),Batroxobin(0.3 BU·kg-1 i.v.bolus),Tirofiban(40 μg·kg-1,i.v.bolus),or vehicle was administered and observations continued for two additional hours.Platelet aggregation induced by adenosine diphosphate(ADP),arachidonic acid(AA),collagen(CG)was measured by the method of born,and thrombin time(TT),prothrombin time(PT),activated partial thromboplastin time(APTT)and fibrinogen(Fbg)were measured using coagulation methods,bleeding time was measured according to previous described methods.Results MV1 dramatically inhibited the frequency of CFR dose-dependently and the frequency of CFR decreased by 65%,80% respectively at 1 h than that in control group's after MV1 0.3,0.6 mg·kg-1 administration,further more the frequency decreased by 75%,90% respectively at 2 h.MV1 eliminated thrombus formation in 5 of 6 dogs at 0.6 mg·kg-1,and the time for CFR absolute disappearances of MV1 at a dose of 0.6 mg·kg-1 was shortened to 5±2 min(the time was more than 120 min in all dogs of control group).Platelet aggregation induced by ADP,AA,CG was inhibited effectively by MV1 0.3,0.6 mg·kg-1 TT,PT prolonged gently after MV1 administration,and MV1 produced an approximate 40% degradation of Fbg,but MV1 did not have any effects on APTT.There was a tendency for prolonged bleeding time with MV1 administration.Conclusions These studies showed that as a novel serine protease,MV1 provides favorable antithrombotic activity in vivo with inhibition of platelet aggregation and fibrinogenolytic activity.The results indicated that MV1 has reliable therapeutical efficacy on unstable angina pectoris.  相似文献   

5.
Aim: To investigate the effects of lithium (Li) and prostaglandin A1 (PGA1) on the expression of heat shock factor 1 (HSF- 1), heat shock proteins (HSP), and apoptosis protease activating factor-1 (Apaf-1) induced by permanent focal ischemia in rats. Methods: The rats were pretreated with a subcutaneous (sc) injection of Li for 2 d or a single intracerebral ventricle (icv) administration of PGA1 for 15 min before ischemic insult, or a combination of Li (sc, 1 mEq/kg, 2 d) and PGA1 (icv, 15 min prior to ischemic insult). Brain ischemia was induced by the permanent middle cerebral artery occlusion (pMCAO). Twenty-four hours after the occlusion, the expression of HSF-1, HSP, and Apaf-1 in the ischemic striatum were examined with Western blot analysis. Results: The expression of HSF-1, heme oxygenase-1 (HO-1), HSP90α, and Apaf-1 were significantly increased, but the expression of HSP90β was significantly decreased 24 h after the pMCAO. PGA1 and Li and their combination significantly enhanced the ischemia-induced elevation in the levels of HSF-1, HO-1, and HSP90α, and recovered HSP90β expression, but decreased Apaf-1 levels in the ischemic striatum. Conclusion: The present study demonstrates that PGA1 and Li have synergistic effects on the enhancement of the expression of HSP, suggesting that the synergistic effects of PGA1 and Li in the rat model of permanent focal cerebral ischemia may be mediated by the enhancement expression of HSP expression and the downregulation of Apaf- 1. Our studies suggest that combined PGA1 and Li may have potential clinical value for the treatment of stroke.  相似文献   

6.
Osthole,a main active constituent from Cnidium monnieri(L.) Cusson,has been considered therapeutic agent in the treatment of ischemic stroke.This study was designed to investigate the effect of osthole on permanent middle cerebral artery occlusion(MCAO) in rats.Osthole was administrated by gavage to the normal and the MCAO rats.Rats were assessed for neurological deficit after 24 h following MCAO,then their brains were evaluated to determine the infarct area,and the mRNA and protein levels of some inflammatory factors were detected.It was found that MCAO animals pre-treated with osthole for 7 d showed significant improvement in all neurological tests compared with vehicle-treated MCAO groups.In addition,there was a significant decrease in infarct volume 24 h after occlusion in animals pre-treated with osthole versus the vehicle-treated MCAO group.MCAO also dramatically caused some inflammatory factors increase.However,pretreatment with osthole restored the mRNA and protein levels of these factors,including TNF-α,IL-1β,COX-2,iNOS of ischemic penumbra cortices,suggesting that osthole possessed the function of preventing brain against ischemic damage,while no significant difference was found in any of normal groups with or without osthole.The present study demonstrated that osthole may be a novel neuroprotective therapy in the treatment of focal ischemic stroke.  相似文献   

7.
AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125I-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases.  相似文献   

8.
The purpose of this review is to present evidence that the lumen of the coronary vascular endothelium is an important site of hormonal action. This review is based on work performed for the last eight years in our laboratories. To demonstrate that selective and exclusive activation or blockade of coronary luminal hormonal receptors is feasible, we have covalently bound to microbeads or large size dextrans (2000 kDa) several hormones or their receptor blockers. These large molecular complexes when administered intravascularly because of their size, remain confined to the blood vessel lumen. The cardiac effects of these large size complexes are identical to those induced by their small size counterparts. The hormones we have used are; adenosine, acetylcholine, bradykinin, substance P, testosterone, and vasopressin. Furthermore, we have also determined the endothelial mediators responsible for the cardiac effects of these hormones. These findings demonstrate that intravascular hormone receptors are indeed  相似文献   

9.
Aim To explore the effects of Zhishi Xiebai Guizhi Decoction (ZXGD) in the treatment of myocardial infarction (MI) using the network pharmacology method and verifying by in vivo experiments and to reveal the underlying mechanism. Methods The chemical components of ZXGD and related targets were retrieved from the TCMSP database. The targets of MI were searched from the GeneCards, OMIM and DisGeNET databases, with the keywords " myocardial infarction" and "MI", and removing duplicates. The intersection of ZXGD and MI targets were obtained, and a protein-protein interaction (PPI) network based on the intersection of active ingredients and disease targets was constructed. The DAVID database was used to conduct GO and KEGG pathway enrichment analysis on the intersection targets. Combined with STRING database and Cytoscape 3.7.2 software, the intersection targets were visualized as a " medicine-component-target-disease" network. The MI mouse model was established by ligation of the left anterior descending coronary artery of the heart. ZXGD was given once a day for 14 days. The cardioprotective effects of ZXGD were examined by ultrasound cardiogram and Western blot. Results The results of network pharmacology analysis showed that the pharmacological components of ZXGD such as quercetin, naringenin, β-sitosterol, and luteolin maybe work on the targets like TNF-α, IL-1β, IL-6, VEGFA, and IL-10. Animal experiments found that compared with the model group, ZXGD significantly increased the left ventricular cardiac function, outflow tract blood flow, and other ultrasound indexes of the mice (P < 0.05). Moreover, the expression levels of IL-1β, TNF-α and IL-6 in myocardial infarction tissue were significantly down-regulated by ZXGD (P < 0.05), while the expression level of IL-10 was significantly up-regulated (P < 0.05). Conclusion ZXGD protects against MI and improves heart function by regulating inflammatory factors including TNF-α, IL-1β, IL-6, and IL-10. © 2023 Publication Centre of Anhui Medical University. All rights reserved.  相似文献   

10.
Brain edema is a common and serious complication of ischemic stroke with limited effective treatment.We previously reported that methylene blue(MB)attenuated ischemic brain edema in rats,but the underlying mechanisms remained unknown.Aquaporin 4(AQP4)in astrocytes plays a key role in brain edema.We also found that extracellular signal-regulated kinase 1/2(ERK1/2)activation was involved in the regulation of AQP4 expression in astrocytes.In the present study,we investigated whether AQP4 and ERK1/2 were involved in the protective effect of MB against cerebral edema.Rats were subjected to transient middle cerebral artery occlusion(tMCAO),MB(3 mg/kg,for 30 min)was infused intravenously through the tail vein started immediately after reperfusion and again at 3 h after ischemia(1.5 mg/kg,for 15 min).Brain edema was determined by MRI at 0.5,2.5,and 48 h after tMCAO.The decreases of apparent diffusion coefficient(ADC)values on diffusion-weighted MRI indicated cytotoxic brain edema,whereas the increase of T2 MRI values reflected vasogenic brain edema.We found that MB infusion significantly ameliorated cytotoxic brain edema at 2.5 and 48 h after tMCAO and decreased vasogenic brain edema at 48 h after tMCAO.In addition,MB infusion blocked the AQP4 increases and ERK1/2 activation in the cerebral cortex in ischemic penumbra at 48 h after tMCAO.In a cell swelling model established in cultured rat astrocyte exposed to glutamate(1 mM),we consistently found that MB(10μM)attenuated cell swelling,AQP4 increases and ERK1/2 activation.Moreover,the ERK1/2 inhibitor U0126(10μM)had the similar effects as MB.These results demonstrate that MB improves brain edema and astrocyte swelling,which may be mediated by the inhibition of AQP4 expression via ERK1/2 pathway,suggesting that MB may be a potential choice for the treatment of brain edema.  相似文献   

11.
目的 探讨低分子肝素钙联合复方丹参滴丸治疗不稳定性心绞痛的临床疗效.方法 81例不稳定型心绞痛患者随机分为2组,对照组39例采用常规治疗.治疗组42例在常规治疗基础上采用复方丹参滴丸20粒,3次/d口服,连用2周;同时应用低分子肝素钙6 000 U皮下注射,1次/d,连用7 d.2组疗程均为2周.结果 治疗组心绞痛临床症状及心电图的总有效率分别为90.48%和76.19%,均显著优于对照组(71.79%和58.97%).治疗组临床疗效和心电图改善均优于对照组(P<0.05).结论 低分子肝素钙联合复方丹参滴丸治疗不稳定型心绞痛安全有效、值得临床推广应用.  相似文献   

12.
The pathogenesis, clinical manifestations and diagnosis, and drug and nondrug therapies of unstable angina pectoris are reviewed. Coronary-artery plaque fissure and rupture, with subsequent platelet aggregation and thrombosis, are the primary underlying stimuli for unstable angina. Unstable angina has been defined as consisting of new-onset angina; angina that is increasing in frequency, intensity, or duration (crescendo angina); or angina at rest. The diagnosis of unstable angina is based on the clinical presentation, electrocardiographic findings, the lack of evidence of myocardial infarction (MI), exercise testing, and coronary angiography. I.V. nitroglycerin is the cornerstone of medical therapy for unstable angina, it relieves chest pain and has a short onset of action. I.V. nitroglycerin, however, has not been shown to reduce the occurrence of MI or death, and its beneficial effects may decrease over time. Aspirin reduces the occurrence of MI and death in patients with unstable angina, but the ideal dosage has not been established. Heparin may reduce the frequency of angina and MI, but its effect on mortality is unknown. Nifedipine has produced beneficial effects in small trials, whereas larger trials have suggested that the drug has deleterious effects when used in the treatment of unstable angina. Verapamil and diltiazem may be effective in relieving chest pain. Calcium-channel blockers have generally not been proved to reduce the risk of MI and death. Data evaluating the efficacy of beta-adrenergic blockers as monotherapy for unstable angina are lacking; these drugs should not be used in patients with vasospastic or Prinzmetal's angina. Thrombolytic therapy has produced mixed results when used in the treatment of unstable angina. Nondrug therapies for unstable angina include intra-aortic balloon counterpulsation, percutaneous transluminal coronary angioplasty, and coronary-artery bypass surgery. Numerous drug and nondrug therapies may be employed in the treatment of unstable angina pectoris.  相似文献   

13.
冠心病是常见缺血性心血管疾病的一种,因冠状动脉粥样硬化导致的心肌缺血、缺氧所致,可引发心绞痛,致使患者病情进一步加重。冠心病、心绞痛的治疗以药物为主,注射用丹参多酚酸是用丹参提取物制成的中药注射剂,具有抗氧化应激、减轻心肌缺血损伤、抗炎等多个方面的药理作用,可有效缓解冠心病、心绞痛症状,促进患者预后改善。对近年来注射用丹参多酚酸盐治疗冠心病、心绞痛的作用机制与临床疗效的研究进展进行综述。  相似文献   

14.
The results obtained in the CAPRIE study in 1996 led to the introduction of the clopidogrel as a new antiplatelet drug in the secondary prevention of acute myocardial infarct (AMI), ischemic stroke (IS) and symptomatic peripheral artery disease (PAD). Clopidogrel showed a similar efficacy and safety than acetylsalicylic acid (ASA). More recently, the combined use of clopidogrel with ASA has evidenced a better protection than ASA alone in some patients: patients with past history of AMI, angina pectoris, intermittent claudication or PAD, IS or TIA, coronary bypass, and diabetes mellitus, patients on treatment with statins, and patients with symptomatic carotid stenosis >/=50%. We review the reported evidence on the efficacy of clopidogrel in the secondary prevention of ischemic stroke.  相似文献   

15.
目的探析冠心病心绞痛患者应用美托洛尔治疗后心率变异性和心肌缺血总负荷的变化。方法90例冠心病心绞痛患者,根据治疗方法不同分为对照组和观察组,每组45例。对照组患者采用常规治疗,观察组患者在常规治疗基础上采用美托洛尔治疗。对比两组患者治疗前后心肌缺血总负荷情况及心率变异性、心绞痛发作情况。结果治疗后,两组患者心肌缺血总负荷均低于本组治疗前,且观察组心肌缺血总负荷(190.2±20.1)明显低于对照组的(285.5±20.4),差异具有统计学意义(P<0.05)。治疗后,观察组患者RR间期平均值标准差(SDANN)、相邻窦性RR间期差值>50 ms的心搏数占窦性RR间期总搏数的百分比(PNN50)、相邻正常RR间期差值的均方(RMSSD)、24 h窦性心搏RR间期的标准差(SDNN)分别为(108.4±12.1)ms、(15.1±3.4)%、(43.6±9.0)ms、(112.4±18.1)ms,均高于对照组的(98.5±11.4)ms、(12.1±3.9)%、(38.4±8.1)ms、(102.1±15.1)ms,差异具有统计学意义(P<0.05)。观察组患者心绞痛持续时间短于对照组,心绞痛发作次数少于对照组,差异具有统计学意义(P<0.05)。结论针对冠心病心绞痛患者,在临床治疗中应用美托洛尔治疗能够改善患者心率变异性,同时明显降低患者心肌缺血总负荷,缓解心绞痛临床症状,具有临床推广应用价值。  相似文献   

16.
OBJECTIVE: To analyse the economic benefits, in comparison with placebo, of the secondary prevention of ischaemic stroke and myocardial infarction (MI) with lysine acetylsalicylate (Kardégic) in patients with a history of ischaemic stroke, MI or stable and unstable angina pectoris. DESIGN AND SETTING: This was a modelling study from the perspectives of direct medical costs, the social security system and society in France. METHODS: Efficacy data for the secondary prevention of ischaemic events were derived from the Antiplatelet Trialists' Collaboration meta-analysis on antithrombotics. The rates and costs of ischaemic disease and of serious gastrointestinal adverse affects arising from long term aspirin treatment, as well as the costs of treatment with lysine acetylsalicylate, were taken from published sources, using French data where possible. RESULTS: From the social security perspective, the estimated cost-effectiveness ratios show that the prevention of MI in patients with a history of unstable angina (with a 1-year follow-up) is a cost-saving strategy, with net benefits ranging from $US5703 (1996 prices) per avoided MI for lysine acetylsalicylate 300 mg/day to $US5761 per avoided MI for lysine acetylsalicylate 75 mg/day. The prevention of MI and stroke is also a cost-saving strategy in patients with prior MI [net benefits in a 2-year follow-up (5% discount rate) ranging from $US15 to $US494 per avoided MI and from $US37 to $US1170 per avoided stroke]. This was also true in patients with prior ischaemic stroke (net benefits in a 3-year follow-up ranging from $US610 to $US2082 per avoided MI and from $US176 to $US599 per avoided stroke). Finally, a 4-year follow-up in patients with a history of stable angina pectoris shows that prophylactic treatment with lysine acetylsalicylate is associated with net costs per avoided MI, ranging from $US4375 to $US3608 per avoided event. Sensitivity analysis confirmed that prophylaxis with lysine acetylsalicylate in patients at high risk of cardiovascular and cerebrovascular events results in savings in social security expenditure. CONCLUSIONS: Our results underline the high economic benefit of using lysine acetylsalicylate to prevent secondary ischaemic stroke and MI in patients at high risk of cardiovascular and/or cerebrovascular events, leading to savings for the social security system and society.  相似文献   

17.
Around 2 million people in the UK have angina pectoris and are therefore at high risk of severe coronary events such as myocardial infarction (MI) or sudden death. Conventional management of patients with stable angina includes glyceryl trinitrate, a beta-blocker, aspirin and a statin, with the aim of controlling symptoms and reducing the risk of a coronary event. For patients unable to tolerate a beta-blocker, the choice is less clear but calcium channel blockers and long-acting nitrates provide effective symptom control. Another option is nicorandil (Ikorel--Rh?ne-Poulenc Rorer), a potassium channel activator licensed for the "prevention and long term treatment of chronic stable angina pectoris". In our review of nicorandil 8 years ago, we concluded that it provided symptom control that was as good as, but no better than, other less expensive anti-anginal drugs. Since then, new data have suggested that nicorandil might reduce the frequency of coronary events in patients with stable angina. Here, we consider these findings and reassess the place of nicorandil for patients with angina.  相似文献   

18.
杜福昌  于洪杰 《江苏医药》1992,18(10):525-528
对113例冠心病心绞痛患者进行了为期2.5年的前瞻性观察。于此期间发生非致死性急性心肌梗塞6例,冠心病猝死1例,非心源性死亡3例。急性心肌梗塞的平均年发生率为2.2%。其中40例不稳定型心绞痛为4.0%,68例稳定型心绞痛为1.2%。经单因素相关及多元逐步回归分析,结果表明心绞痛程度、病型及阵发性缺血型ST-T 改变的程度为其影响预后的主要决定因素,吸烟及动脉血压增高也为不利因素。  相似文献   

19.
W S Aronow 《Drugs & aging》2001,18(11):807-818
Aspirin (acetylsalicylic acid) should be administered to patients on day 1 of an acute myocardial infarction (MI) and continued indefinitely. Early intravenous beta-blockade should be used during acute MI. beta-blockers should be continued indefinitely. Angiotensin-converting enzyme (ACE) inhibitors should be used in patients with acute MI with ST-segment elevation in two or more anterior precordial leads. ACE inhibitors should be used during and after acute MI in patients with chronic heart failure (CHF) or with a left ventricular ejection fraction < or =40%. There are no class I indications for using calcium channel antagonists during and after acute MI. Intravenous heparin should be used in patients with acute MI undergoing coronary revascularisation and in patients at high risk for systemic embolisation. Enoxaparin should be used in patients with non-Q-wave MI. Thrombolytic therapy should be considered in patients with acute MI with ST-segment elevation in contiguous leads of a 12-lead electrocardiogram or with left bundle branch block. Platelet glycoprotein IIb/IIIa inhibitors should be administered intravenously as an adjunct to heparin and aspirin in patients with non-Q-wave MI. Intravenous nitroglycerin should be used: (i) for the first 24 to 48 hours in patients with acute MI and CHF, large anterior MI, persistent ischaemia or hypertension; and (ii) continued beyond 48 hours in patients with recurrent angina pectoris or persistent pulmonary congestion. Long-acting nitrates should be given after MI, along with beta-blockers, to patients with angina pectoris. There are no class I indications for using intravenous magnesium during acute MI. The routine use of antiarrhythmic drugs other than beta-blockers during and after acute MI is not recommended.  相似文献   

20.
国产左旋卡尼汀佐治不稳定型心绞痛临床观察   总被引:4,自引:0,他引:4  
目的评价国产左旋卡尼汀对不稳定型心绞痛的临床疗效。方法选择不稳定型心绞痛患者112例,随机分为A、B两组,A组给予常规治疗;B组在常规治疗基础上加国产左旋卡尼汀3.0g静滴,每日1次,并观察下述指标:①静息心电图;②心绞痛发作的次数;③心绞痛发作持续的时间;④不良反应。治疗结束评定两组心绞痛稳定情况。结果B组可明显改善静息心电图心肌缺血的表现,总有效率为80.3%,与A组(60.7%)比较差异有显著意义(P<0.05);B组与A组心绞痛的总有效率分别为96.42%、91.07%,P>0.05,但左卡组心绞痛显效率较常规组高(87.50%/64.28%)。结论国产左旋卡尼汀佐治不稳定型心绞痛安全有效,值得临床推广。  相似文献   

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