姜黄素衍生物对糖尿病小鼠糖耐量及脂代谢的影响

目的观察姜黄素（Cur）衍生物对糖尿病模型小鼠糖耐量及脂代谢的影响。方法以芳香醛、乙酰丙酮为原料,通过Claisen-Schmidt缩合制备Cur衍生物L3,以Cur为原料氢化还原得到四氢姜黄素。化合物L3,四氢姜黄素,Cur和普罗布考对链脲佐菌素诱导糖尿病模型小鼠灌胃给药,葡萄糖氧化酶法测血糖,酶比色法测总胆固醇和甘油三酯。SPSS13.0软件处理数据并做生存分析曲线。结果化合物L3灌胃1 g.kg-1.d-1可提高生存率,改善糖尿病高血脂的糖耐量,降低血清总胆固醇。结论化合物L3具有改善糖尿病模型小鼠脂代谢的新功能。     

Antioxidants: Benefits and risks for long-term health

The oxidative modification hypothesis postulates that oxidative stress is one of the major factors in aging and the development of age-related disorders, including cardiovascular diseases. In this scenario, the oxidative modification of lipids, proteins and nucleic acids in vascular walls contributes to the etiology of cardiovascular disease, implying that consumption or therapeutic use of antioxidants could prevent the onset of such pathological disorders. Because of this, a number of studies have been conducted to address the question of whether cardiovascular diseases can be modulated by antioxidant treatment or consumption. Although some of the earliest data, collected in animal studies and epidemiologic studies have shown a measure of success, numerous clinical trials indicate that this approach is of minimal or no benefit. These conclusions represent a challenge to design more sensitive antioxidant trials in order to confirm or alter these conclusions. The focus of this review is on the benefits and disadvantages associated with the use of antioxidants, such as vitamins C and E, polyphenols, or antioxidant therapies, including hormone replacement therapy and iron reduction therapy, on overall vascular health.     

普罗布考和辛伐他汀联合治疗脑动脉狭窄的疗效观察

目的探讨脑动脉狭窄药物治疗的疗效。方法回顾性分析2007至2010年经颅多普勒检查诊断的脑动脉狭窄患者240例。将240例大脑中脑动脉狭窄患者随机分成4组,A组联合应用普罗布考与辛伐他汀进行治疗。B组应用辛伐他汀进行治疗。C组应用普罗布考治疗。D组应用阿司匹林作为对照组。分别于用药前、用药后3~24个月随访,记录不良反应事件发生情况,复查TCD检查结果将血管转归分为好转组、稳定组、进展组,评价其预后并就药物疗效进行分析。结果 A组总有效率25%,B组有效率18.3%,C组20%,D组13.3%。结论联合用药效果好于单一用药及不用药物,有统计学意义,P<0.01。普罗布考及辛伐他汀比较无统计学差异。应用药物效果好于不用药物。有统计学意义,P<0.01。对于脑动脉狭窄的患者,如未行手术治疗,可应用药物治疗。     

Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.     

AGI-1067, a novel antioxidant and anti-inflammatory agent,enhances insulin release and protects mouse islets

The antioxidant and anti-inflammatory compound AGI-1067 (succinobucol) has potential as an oral anti-diabetic agent. AGI-1067 reduces H_bA1c, improves fasting plasma glucose, and reduces new-onset diabetes. We investigated AGI-1067 for possible effects on mouse pancreatic islets in vitro. Pretreatment with 10 μM AGI-1067 increased glucose-stimulated insulin secretion (11 mM) without affecting secretion in basal (3 mM) glucose. AGI-1067 enhanced the intracellular calcium response to glucose stimulation in 7 mM and 11 mM glucose, but had no effect in 28 mM or basal glucose. AGI-1067-pretreated islets also showed enhanced calcium responses to methyl pyruvate and alpha-ketoisocaproate at low doses, but not high doses. The AGI-1067-mediated effects on glucose-stimulated calcium were maintained during continuous diazoxide exposure, suggesting effects on the K_ATP-channel-independent pathway. AGI-1067 also reduced cytokine-induced islet cell death and expression of iNOS, a key component in cytokine signaling. This is the first report of direct stimulatory and protective effects of a first-in-class potential anti-diabetic agent on pancreatic islets.     

丙丁酚改善缺血性心肌病心力衰竭患者心功能及机制研究

目的:探讨丙丁酚改善缺血性心肌病(is-chemic cardiomyopathy,ICM)心力衰竭患者心功能及其机制。方法:选择36例ICM心力衰竭患者,随机分为丙丁酚组和常规治疗组,各18例。两组患者均接受调脂、抗血小板和抗心肌缺血的基础治疗以及常规抗心衰治疗,丙丁酚组在常规治疗基础上加用丙丁酚片。治疗初及治疗6个月后观察两组患者下列指标的变化情况:NYHA心功能分级;血脂指标:TC、TG、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);氧化应激指标:氧化低密度脂蛋白(ox-LDL)、丙二醛(MDA)、超氧化物岐化酶(SOD);炎症标志物:高敏C反应蛋白(hs-CRP)、红细胞沉降率(ESR);超声心动图指标:左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)和左室射血分数(LVEF)。结果:治疗6个月后,与常规治疗组比较,丙丁酚组患者MDA明显降低(P<0.05),ox-LDL明显降低(P<0.01),SOD明显增高(P<0.01),NYHA心功能分级有效率明显增加(P<0.05),LVEF有增加的趋向,但比较差异无统计学意义(P>0.05)。治疗6个月后,与常规治疗组比较,丙丁酚对于TG、HDL-C、LDL-C、hs-CRP、ESR、LVEDD和LVESD的改变无统计学意义。结论:丙丁酚改善ICM心力衰竭患者心衰的作用与其抗氧化作用有关,与其调脂作用无关。     

复方丹参滴丸、普罗布考对动脉损伤后内膜增殖与血管重塑的影响

目的：探讨复方丹参滴丸、普罗布考对兔髂动脉损伤后内膜增殖、血管重塑及血管内皮生长因子表达的影响。方法：雄性日本大耳白兔40只,随机平均分为对照组、普罗布考组、复方丹参滴丸组和联合组,高脂喂养两周后行髂动脉球囊内皮拉伤术,从术前3d开始对照组予单纯高脂喂养,治疗组分别以普罗布考（1．0g／只·d^-1）、复方丹参滴丸（300mg／只·d^-1）及两药联合灌喂至术后4周,取病变血管行病理形态学观察,免疫组化检测血管内皮生长因子（VEGF）和增殖细胞核抗原（PCNA）表达水平。结果：与对照组比较,普罗布考组、复方丹参滴丸组增殖内膜面积明显减小（P〈0．05）,普罗布考组内弹力膜包绕面积增大（P〈0．05）;与单独用药组比较,联合组内弹力膜包绕面积明显增大（P〈0．05）,但增殖内膜面积无改变（P〉0．05）;各治疗组VEGF、PCNA表达均较对照组明显减少（P〈0．05）。结论：复方丹参滴丸、普罗布考均可抑制动脉损伤后平滑肌细胞增殖,减轻内膜增生;普罗布考兼有改善血管重塑的作用,两药联合使用可取得改善血管重塑的协同效应,其机制可能与减少VEGF在血管内、中膜的表达水平有关。     

普罗布考对高血压合并糖尿病患者尿微量白蛋白影响

目的探讨抗氧化剂普罗布考对高血压病合并糖尿病患者尿微量白蛋白的影响。方法选正常对照组60例,高血压病合并糖尿病患者88例,高血压病患者110例,糖尿病（非胰岛素治疗）患者92例,分别测血尿陉微球蛋白（β2-MG）和尿微量白蛋白（Alb）,在降压降糖基础上并用抗氧化剂普罗布考治疗高血压病合并糖尿病患者12周,测血尿β2-MG和尿微量Alb。结果与正常对照组相比,其他各组血尿β2-MG、尿Alb均较高,抗氧化剂普罗布考治疗高血压病合并糖尿病患者后,血尿β2-MG、尿Alb、较治疗前减低（P〈0．05）。结论高血压、糖尿病均使血尿＆MG和尿微量Alb升高,高血压病合并糖尿病更甚,抗氧化剂普罗布考有助于降低尿微量白蛋白,保护肾功能。     

普罗布考抗动脉粥样硬化作用机制及研究进展

早期大量的药理及临床实验发现,普罗布考具有降低血脂、抗氧化、抗炎等作用,但由于其可降低高密度脂蛋白胆固醇(HDL-C),使其在临床上的应用受到影响。近年的研究证明,普罗布考虽然降低血HDL-C浓度,但并不降低其转运胆固醇酯的作用,甚至增加其转运能力,并可稳定和消退动脉粥样硬化斑块,改善血管内皮功能,减少动脉粥样硬化的发生、发展。现就普罗布考抗动脉粥样硬化作用机制的研究新进展予以综述。     

普罗布考联合他汀类药物治疗对ACS患者血清脂联素、血脂水平的影响

目的观察单纯应用他汀类药物与普罗布考联合他汀类药物两种不同治疗方法对急性冠脉综合征患者治疗前后血清脂联素及血脂水平变化的影响。方法选择2008年10月至2009年10月住院期间确诊为急性冠脉综合征患者80例,按随机化原则分为2组：常规治疗组（40例）与联合普罗布考组（40例）。常规治疗组给予他汀类药物、抗血小板药物、硝酸酯、血管紧张素转换酶抑制剂（ACEI）及β受体阻滞剂;联合普罗布考组在上述治疗基础上加用普罗布考。2组病例均在入院后第1日和治疗1周后（入院第8天）晨起采集空腹静脉血检测脂联素、血脂。观察两种不同治疗方法对血清脂联素、血脂水平的影响。结果治疗后2组血清胆固醇、低密度脂蛋白胆固醇水平明显下降（P均〈0.05）,甘油三酯下降程度联合普罗布考组较常规治疗组明显（P〈0.05）,而2组血清胆固醇、低密度脂蛋白胆固醇水平变化值无明显差异（P均〉0.05）。2组脂联素治疗后均显著升高（P均〈0.05）,联合普罗布考组治疗后上升幅度明显高于常规治疗组（P〈0.05）。结论普罗布考联合他汀类药物治疗有益于急性冠脉综合征患者血中保护性因素脂联素的升高及血脂水平的改善,可改善预后。