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浙江大学学报（医学版） 2015年第5期44卷 479-485页

作者：陈子博常琳琳周恬伊王丹丹陈瑛赵平鸽朱虹浙江大学药学院浙江省抗肿瘤药物临床前研究重点实验室浙江杭州310058 浙江省义乌市中心医院浙江义乌322000

目的：研究舒尼替尼通过调控转化生长因子β（TGF—β）介导的上皮-间质转化抑制卵巢癌细胞转移的作用和机制。方法：运用划痕实验和transwell实验考察舒尼替尼对卵巢癌细胞SKOV3运动能力的影响；采用蛋白质印迹法、实时定量PCR技术和... 详细信息

目的：研究舒尼替尼通过调控转化生长因子β（TGF—β）介导的上皮-间质转化抑制卵巢癌细胞转移的作用和机制。方法：运用划痕实验和transwell实验考察舒尼替尼对卵巢癌细胞SKOV3运动能力的影响；采用蛋白质印迹法、实时定量PCR技术和免疫荧光技术分析舒尼替尼对TGF-β诱导的钙黏蛋白（E—cadherin）表达的影响；并通过蛋白质印迹法和报告基因检测技术分析舒尼替尼对Snail蛋白水平和Smad转录活性的影响。结果：舒尼替尼可抑制SKOV3细胞的迁移运动，且呈现一定的量效关系。TGF—β刺激SKOV3细胞后，细胞内E-cadherin蛋白表达减少，而舒尼替尼可部分回调TGF—β减少的E—cadherin。TGF—β可诱导Snail蛋白上调，而该效应可被舒尼替尼阻断；TGF-β可增强Smad复合物的转录活性，而舒尼替尼则可削弱TGF—β对该转录活性的诱导作用。结论：舒尼替尼通过干预Smad复合物的转录活性阻断Snail对E—cadherin的负性调控，从而抑制卵巢癌SKOV3细胞发生上皮-间质转化，并干预其运动迁移能力。

关键词：卵巢肿瘤/病理学间质细胞/病理学上皮细胞/病理学肿瘤转移吡咯类/治疗应用吲哚类/治疗应用钙黏着糖蛋白类/生物合成转录因子/生物合成

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阿托伐他汀可改善急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗后无复流现象

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浙江大学学报（医学版） 2016年第5期45卷 530-535页

作者：严凌叶露汪坤周杰朱春甲安徽省铜陵市人民医院心内科

目的：观察不同剂量阿托伐他汀治疗前后急性ST段抬高型心肌梗死（STEMI）患者血清尿酸水平的变化及其与经皮冠状动脉介入（PCI）治疗后无复流的关系。方法：连续选择安徽省铜陵市人民医院2013年6月至2015年12月入院的114例STEMI患者。... 详细信息

目的：观察不同剂量阿托伐他汀治疗前后急性ST段抬高型心肌梗死（STEMI）患者血清尿酸水平的变化及其与经皮冠状动脉介入（PCI）治疗后无复流的关系。方法：连续选择安徽省铜陵市人民医院2013年6月至2015年12月入院的114例STEMI患者。所有患者在发病后12h内行PCI治疗。按照PCI治疗前口服阿托伐他汀剂量的不同，将患者随机分为常规剂量组（55例，阿托伐他汀20mg）和大剂量组（59例，阿托伐他汀80mg）；然后根据患者初始血清尿酸水平将两组各分为正常尿酸组及高尿酸血症组。观察用药前后两组尿酸水平、PCI治疗后冠状动脉血流的变化。分析尿酸下降幅度、阿托伐他汀剂量与PCI治疗后冠状动脉血流之间的相关性。结果：用药后，常规剂量组和大剂量组患者的尿酸水平均显著下降（均P〈0．05），且高尿酸血症患者比正常尿酸患者血清尿酸下降幅度更大（均P〈0．05）。与常规剂量组比较．大剂量组高尿酸血症患者的尿酸下降幅度更大（P〈0．05）；但两组中正常尿酸患者的尿酸下降幅度比较差异无统计学意义（P〈0．05）。两组共发生无复流19例，发生率为16．7％。其中，常规剂量组发生无复流12例，正常尿酸者3例，高尿酸血症者9例，两者差异有统计学意义（P〈0．01）；大剂量组发生无复流7例，正常尿酸者2例，高尿酸血症者5例，两者差异也有统计学意义（P〈0．05）。多因素Logistic回归分析结果显示，高尿酸血症等因素是直接PCI治疗后无复流现象的独立危险因素（OR=1．01，95％可信区间：1．01-1．11，P〈0．01）。阿托伐他汀常规剂量组无复流的发生率为21．8％（12／55），大剂量组为11．9％（7／59），差异有统计学意义（P〈0．01）。结论：大剂量阿托伐他汀可能通过降低血尿酸水平改善直接PCI治疗后无复流，通过大剂量阿托伐他汀干预有望改善STEMI患者直接PCI治疗冠状动脉无复流。

关键词：高尿酸血症/药物疗法心肌梗死/治疗血管成形术,经腔,经皮冠状动脉/方法庚酸类/治疗应用吡咯类/治疗应用无复流现象

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阿托伐他汀对肺纤维化大鼠肺泡灌洗液MMP-9和TIMP-1的影响

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浙江大学学报（医学版） 2011年第1期40卷 64-70页

作者：魏路清董彦李振华武警医学院附属医院天津300162 中国医科大学呼吸疾病研究所辽宁沈阳110001

目的:观察阿托伐他汀对肺纤维化大鼠肺泡灌洗液及血清MMP-9和TIMP-1的影响。方法:雌性Wistar大鼠35只,随机分成对照组(向气管内注入生理盐水0.2~0.3 ml),模型2、4、6周组和阿托伐他汀干预2、4、6周组,每组5只。气管注入博莱霉素制备大... 详细信息

目的:观察阿托伐他汀对肺纤维化大鼠肺泡灌洗液及血清MMP-9和TIMP-1的影响。方法:雌性Wistar大鼠35只,随机分成对照组(向气管内注入生理盐水0.2~0.3 ml),模型2、4、6周组和阿托伐他汀干预2、4、6周组,每组5只。气管注入博莱霉素制备大鼠肺纤维化模型,建模后次日模型组和阿托伐他汀干预组大鼠每日胃内分别灌注生理盐水(2 ml)和生理盐水溶解的阿托伐他汀2 ml(10 mg/kg体重),于2周、4周及6周处死大鼠。ELISA方法检测肺泡灌洗液和血清中MMP-9、TIMP-1的质量浓度。结果:阿托伐他汀干预组肺泡炎及肺纤维化程度较模型组减轻,以6周组明显。血清中MMP-9、TIMP-1质量浓度各组间无统计学差异(P>0.05)。在肺泡灌洗液中,模型2周组、6周组的MMP-9质量浓度均高于对照组(P<0.01、P<0.05),而阿托伐他汀干预2周组、4周组及6周组的MMP-9质量浓度比对应的模型组均有所降低,其中2周组、4周组的MMP-9仍高于对照组,6周组与对照组相比无统计学差异。模型2周组肺泡灌洗液中的TIMP-1质量浓度与对照组相比无统计学差异,4周组、6周组高于对照组,有统计学差异(P<...

关键词：博莱霉素/副作用肺纤维化/药物疗法庚酸类/治疗应用吡咯类/治疗应用明胶酶B/血液金属蛋白酶1组织抑制剂/血液支气管肺泡灌洗液

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The antitussive activity of δ-opioid receptor stimulation in guinea pigs

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期292卷 803-809页

作者： Kotzer, CJ Hay, DWP Dondio, G Giardina, G Petrillo, P Underwood, DC SmithKline Beecham Pharmaceut Dept Pulm Pharmacol King Of Prussia PA 19406 USA SmithKline Beecham Pharmaceut Dept Med Chem King Of Prussia PA 19406 USA SmithKline Beecham Pharmaceut Dept Biol King Of Prussia PA 19406 USA

In this study, the activity of the delta-opioid receptor subtype-selective agonist, SB 227122, was investigated in a guinea pig model of citric acid-induced cough. Parenteral administration of selective agonists of the delta-opioid receptor (SB 227122), mu-opioid receptor (codeine and hydrocodone), and kappa-opioid receptor (BRL 52974) produced dose-related inhibition of citric acid-induced cough with ED50 values of 7.3, 5.2, 5.1, and 5.3 mg/kg, respectively. The nonselective opioid receptor antagonist, naloxone (3 mg/kg, i.m.), attenuated the antitussive effects of codeine or SB 227122, indicating that the antitussive activity of both compounds is opioid receptor-mediated. The delta-receptor antagonist, SB 244525 (10 mg/kg, i.p.), inhibited the anti-tussive effect of SB 227122 (20 mg/kg, i.p.). In contrast, combined pretreatment with beta-funaltrexamine ( mu-receptor antagonist;20 mg/kg, s.c.) and norbinaltorphimine (kappa-receptor antagonist;20 mg/kg, s.c.), at doses that inhibited the antitussive activity of m-and kappa-receptor agonists, respectively, was without effect on the antitussive response of SB 227122 (20 mg/kg, i.p.). The sigma-receptor antagonist rimcazole (3 mg/kg, i.p.) inhibited the antitussive effect of dextromethorphan (30 mg/kg, i.p.), a sigma-receptor agonist, but not that of SB 227122. These studies provide compelling evidence that the antitussive effects of SB 227122 in this guinea pig cough model are mediated by agonist activity at the delta-opioid receptor.

关键词： CHO细胞卡唑类/药理学细胞系克隆生物可待因/药理学咳嗽/预防和控制仓鼠亚科右美沙芬/药理学疾病模型动物剂量效应关系药物药物相互作用氢可酮/药理学左洛啡烷/类似物和衍生物左洛啡烷/治疗应用纳洛酮/药理学麻醉品拮抗药/药理学蛋白质结合吡啶类/药理学吡咯类/治疗应用吡咯烷类/药理学受体阿片样 δ/激动剂受体阿片样 δ/药物作用受体阿片样 δ/生理学受体阿片样 κ/激动剂受体阿片样 κ/药物作用受体阿片样 κ/生理学受体阿片样 μ/激动剂受体阿片样 μ/药物作用受体阿片样 μ/生理学动物豚鼠人类男(雄)性

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Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第1期86卷 46-52页

作者： Blair, SN Capuzzi, DM Gottlieb, SO Nguyen, T Morgan, JM Cater, NB Cooper Inst Dallas TX 75230 USA Thomas Jefferson Univ Jefferson Med Coll Philadelphia PA 19107 USA Midatlantic Cardiovasc Associates Baltimore MD USA Mayo Clin Rochester MN USA Univ Texas SW Med Ctr Dallas TX USA

This study compares the effect of plant stanol ester spread with a placebo spread on cholesterol in patients taking statin therapy, but who still had elevated low-density lipoprotein (LDL) cholesterol. This was a randomized, double-blind, placebo-controlled clinical trial, with 67 women and 100 men with LDL cholesterol greater than or equal to 130 mg/dl and triglycerides less than or equal to 350 mg/dl who had been taking a stable dose of a statin drug for at least 90 days before the start of the study. For 8 weeks, participants consumed 3 servings/day of the plant stanol ester spread that provided 5.1 g/day of plant stanol ester or a placebo. The addition of plant stanol ester spread significantly reduced total cholesterol and LDL cholesterol at 2, 4, and 8 weeks when compared with placebo spread. Plant stanol ester spread reduced total cholesterol at 8 weeks by 12% compared with a placebo reduction of 5% (-7% difference;p <0.0001). Plant stanol ester spread reduced LDL cholesterol at 8 weeks by 17% compared with a 7% reduction in the placebo group (-10% difference, p <0.0001). The absolute reduction in LDL cholesterol at 8 weeks was 24 and 10 mg/dl in the stanol ester and placebo groups, respectively. The plant stanol ester spread group also had greater reductions in both serum total cholesterol and LDL cholesterol than the placebo group at 2 and 4 weeks (p <0.001 for all comparisons). Both spreads were well tolerated by study participants, and no significant adverse events were noted. Consumption of spread that provided 5.1 g/day of plant stanol esters effectively reduced elevated total and LDL cholesterol levels in participants on a stable regimen of a statin. (C) 2000 by Excerpta Medico, Inc.

关键词：高胆固醇血症/血液高胆固醇血症/药物疗法人造黄油普伐他丁/投药和剂量普伐他丁/治疗应用吡咯类/投药和剂量吡咯类/治疗应用斯伐他汀/投药和剂量斯伐他汀/治疗应用谷甾醇/投药和剂量谷甾醇/治疗应用治疗结果甘油三酯类/血液男(雄)性中年人

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RESULTS OF A ONE-YEAR TRIAL OF TOLMETIN IN PATIENTS WITH RHEUMATOID-ARTHRITIS

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JOURNAL OF CLINICAL PHARMACOLOGY 1975年第5-6期15卷 455-463页

作者： BROWN, JH HULL, J BIUNDO, JJ LOUISIANA STATE UNIV SCH MEDDEPT MEDNEW ORLEANSLA 70118 LOUISIANA STATE UNIV SCH MEDDEPT PHARMACOLNEW ORLEANSLA 70118

The safety and effectiveness of tolmetin was assessed in ten patients with active rheumatoid arthritis for 12 months. All patients met the requirements of the American Rheumatism Association's diagnostic criteria for definite rheumatoid arthritis. None of the patients had received gold, antimalarials, or glucocorticoids. All had been stabilized, more or less, with aspirin. Monthly measurements were made of grip strength, duration of morning stiffness, time to the onset of fatigue, Westergren sedimentation rates, the number of swollen joints, number of hot joints, the time to walk 50 feet, and the circumference of proximal interphalangeal (PIP) joints (measured in millimeters with a plastic-loop arthrocircameter). The initial dosage of tolmetin in all patients was 600 mg a day, given orally in three divided doses. Upon completion of the study, the average daily oral dosage was 1400 mg tolmetin. No other antiinflammatory drugs were allowed. The results indicate that tolmetin affords symptomatic relief of rheumatoid arthritis; its use results in global improvement in 80 per cent of the patients, and a net improvement in one or more of the parameters used to assess disease activity in 100 per cent of the patients; it seems to be sufficiently safe to administer to patients over a long period of time; there was no evidence of severe toxicity of any kind; gastrointestinal side effects were uncommon, and epigastric distress, in particular, was not observed.

关键词：关节炎类风湿/药物疗法关节炎类风湿/病理学苯甲酸盐类/治疗应用血沉用力指/病理学关节/病理学吡咯类/治疗应用类风湿因子/分析时间因素人类中年人

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Effect of statin therapy on restenosis after coronary stent implantation

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第8期85卷 962-968页

作者： Walter, DH Schächinger, V Elsner, M Mach, S Auch-Schwelk, W Zeiher, AM Goethe Univ Frankfurt Dept Internal Med 4 Div Cardiol D-60590 Frankfurt Germany

The effect of statins on the development of restenosis and clinical outcome after coronary stent implantation was assessed in a retrospective analysis of 525 consecutive patients. Baseline clinical, angiographic, and procedural characteristics did not differ between 258 patients with and 267 patients without statin therapy. Statin therapy was associated with a significantly (p <0.04) improved survival free of myocardial infarction and a significant reduction in repeat target vessel revascularization procedures (27.9% vs 36.7%, p <0.05) during 6-month follow-vp. Minimal lumen diameter was significantly larger (1.98 +/- 0.88 vs 1.78 +/- 0.88 mm, p = 0.01), late lumen loss was significantly less (0.64 +/- 0.8 vs 0.8 +/- 0.8 mm, p = 0.032), and net gain significantly increased (1.2 +/- 0.88 vs 0.98 +/- 0.92 mm, p = 0.009) in patients receiving statin therapy. Dichotomous angiographic restenosis (greater than or equal to 50%) rates were significantly lower, with 25.4% in the statin group compared with 38% in the no-statin group (p <0.005), Multivariate analysis identified statin therapy (p = 0.005), minimal lumen diameter immediately after stenting (p = 0.02), and stent length (p = 0.02) as independent predictors for subsequent restenosis development. Thus, statin therapy is associated with reduced recurrence rates and improved clinical outcome after coronary stent implantation. (C) 2000 by Excerpta Medica, Inc.

关键词：抗胆固醇血症药/治疗应用病例对照研究冠状血管造影术冠心病/流行病学冠心病/放射摄影术冠心病/治疗无病生存脂肪酸类单不饱和/治疗应用随访研究庚酸类/治疗应用增生吲哚类/治疗应用洛伐他汀/治疗应用吡咯类/治疗应用复发回顾性研究斯伐他汀/治疗应用支架时间因素血管内膜/病理学女(雌)性人类男(雄)性中年人

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Medical therapy versus coronary angioplasty in stable coronary artery disease: A critical review of the literature

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第3期36卷 668-673页

作者： Blumenthal, RS Cohn, G Schulman, SP Johns Hopkins Univ Hosp Div Cardiol Baltimore MD 21287 USA Cleveland Clin Florida Dept Med Ft Lauderdale FL USA

The recent publication of the Atorvastatin Versus Revascularization Treatment (AVERT) trial has renewed debate on the optimal management strategy for relatively stable patients with coronary artery disease. Currently, coronary angiography and percutaneous coronary intervention are often performed in stable patients with good exercise tolerance who have not been treated with proven medications such as aspirin, statins and beta-adrenergic blocking agents in conjunction with comprehensive lifestyle modification. We review the results of prior trials comparing medical therapy with angioplasty and assess their strengths and limitations and then make conclusions about the aggregate data. Next, we describe the ongoing Clinical Outcome Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, which will be the largest of the studies comparing optimal medical therapy and percutaneous revascularization. This study will employ intensive medical management in all patients with coronary;disease, and the incremental benefit of state of the art revascularization techniques in terms of clinical event reduction, quality of life issues and cost-effectiveness will be addressed. For now, aggressive medical therapy and revascularization should be viewed as complementary rather than opposing strategies. All patients with coronary heart: disease should receive proven medical and lifestyle prescriptions to favorably alter the atherosclerotic process. Percutaneous revascularization without comprehensive risk factor modification is a suboptimal therapeutic strategy. (J Am Coil Cardiol 2000;36: 668-73) (c) 2000 by the American College of Cardiology

关键词：血管成形术气囊冠状动脉抗胆固醇血症药/治疗应用冠心病/药物疗法冠心病/外科学冠心病/治疗庚酸类/治疗应用心肌缺血/药物疗法心肌缺血/外科学心肌缺血/治疗心肌血管重建术吡咯类/治疗应用随机对照试验(主题) 人类

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Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia

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AMERICAN HEART JOURNAL 2002年第6期144卷 1044-1051页

作者： Olsson, AG Istad, H Luurila, O Ose, L Stender, S Tuomilehto, J Wiklund, O Southworth, H Pears, J Wilpshaar, JW Linkoping Univ Hosp Dept Med & Care S-58185 Linkoping Sweden Sahlgrens Univ Hosp Gothenburg Sweden Theresegate Legesenter Oslo Norway Lipid Klinikken Oslo Norway Laakariasema KOY Oy Helsinki Finland Natl Inst Publ Hlth Helsinki Finland Univ Helsinki Helsinki Finland Gentofte Univ Hosp Copenhagen Denmark

Background Despite the demonstrated benefits of low-density lipoprotein cholesterol (LDL-C) reduction in reducing the risk of coronary heart disease, many patients receiving lipid-lowering therapy fail to achieve LDL-C goals. We compared the effects of rosuvastatin and atorvastatin in reducing LDL-C and achieving LDL-C goals in patients with primary *** and Results In this 52-week, randomized, double-blind, multicenter trial (4522IL/0026), 412 patients with LDL-C 160 to <250 mg/dL received a 5-mg dose of rosuvastatin (n = 138), a 10-mg dose of rosuvastatin (n = 134), or a 10-mg dose of atorvastatin (n = 140) for 12 weeks; during the following 40 weeks, dosages could be sequentially doubled up to 80 mg if National Cholesterol Education Program Adult Treatment Panel II (ATP-II) LDL-C goals were not achieved. At 12 weeks, 5- and 10-mg doses of rosuvastatin were associated with significantly greater LDL-C reductions than 10-mg doses of atorvastatin (46% and 50% vs 39%, both P < .001). At 12 weeks, both rosuvastatin dosages brought more patients to within ATP-II and European LDL-C goals than atorvastatin (86% and 89% vs 73% and 75%, and 86% vs 55%, respectively). At 52 weeks, compared with atorvastatin, both initial rosuvastatin treatment groups significantly reduced LDL-C (47% and 53% vs 44%, P < .05 and P < .001). Overall, more patients in the initial rosuvastatin 10-mg group achieved their ATP-II LDL-C goal than those in the initial atorvastatin 10-mg group (98% vs 87%), with 82% of patients treated with rosuvastatin achieving their goal at the 10-mg starting dosage without the need for titration, compared with 59% of patients treated with atorvastatin. Both treatments were well tolerated over 52 *** Compared with atorvastatin, rosuvastatin produced greater reductions in LDL-C, which may offer advantages in LDL-C goal attainment over existing lipid-lowering therapies.

关键词：抗胆固醇血症药/治疗应用胆固醇 LDL/血液双盲法氟苯类/治疗应用庚酸类/治疗应用羟甲基戊二酰基CoA还原酶抑制剂/治疗应用高胆固醇血症/血液高胆固醇血症/药物疗法嘧啶类吡咯类/治疗应用磺胺类成年人老年人女(雌)性人类男(雄)性中年人

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Early introduction of HMG-CoA reductase inhibitors could prevent the incidence of transplant coronary artery disease

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TRANSPLANTATION PROCEEDINGS 2000年第2期32卷 331-333页

作者： Kato, T Tokoro, T Namii, Y Kobayashi, T Hayashi, S Yokoyama, I Morimoto, S Chan, M Giannetti, N Hunt, SA Nagoya Univ Sch Med Dept Surg 2 Nagoya Aichi 4668550 Japan Stanford Univ Dept Cardiol Stanford CA 94305 USA Fujita Hlth Univ Sch Med Dept Cardiol Fujita Japan

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