辛伐他汀联合左旋精氨酸对自体移植静脉保护作用的实验研究

目的研究辛伐他汀联合左旋精氨酸对兔颈外静脉移植至股动脉后的保护作用,并探讨可能的机制。方法50只新西兰大白兔,随机分为辛伐他汀实验组、生理盐水对照组。术前3 d开始采用灌胃法给予辛伐他汀（10 mg/Kg溶于10 ml生理盐水）,经耳缘静脉给予左旋精氨酸（100 mg/kg）,对照组给与等量生理盐水,每天一次,直至术后取材。所有动物于术日建立自体静脉旁路移植模型：利用显微外科技术将颈外静脉端侧吻合于股动脉,于术后4周取血管桥标本,同时取0.5 cm移植静脉作为正常静脉参照。光镜下观察、测定移植静脉内膜中膜厚度变化。扫描电镜观察近吻合口处和中央部静脉桥的管腔狭窄程度（管腔增生面积与管腔面积比（S1/S2）,统计学分析各组间差异。结果移植4周后,各组静脉均有内膜及中膜较正常颈静脉明显增厚表现,辛伐他汀组内膜及中膜增厚较对照组轻。两组静脉桥的管腔狭窄程度进行比较存在明显差异。结论（1）兔颈外静脉移植至股动脉后内膜及中膜增厚。（2）辛伐他汀联合左旋精氨酸能抑制动脉化静脉内膜及中膜增厚,有减轻桥静脉狭窄的作用。     

辛伐他汀对高血压病患者左室重量和血管内皮功能的影响及其间的关系

目的探讨辛伐他汀对高血压病（EH）患者左室重量（LVM）和内皮功能的影响及其间的关系。方法 76例EH患者被随机分为各3 8例的Ⅰ（口服辛伐他汀和利尿剂）、Ⅱ组（口服利尿剂）,超声研究受检者治疗12周前后左室重量指数（LVMI）并结合高频超声观察肱动脉内皮依赖性扩张（DIRH）及非内皮依赖性扩张功能（DING）。30例正常人作为对照组。结果治疗前Ⅰ、Ⅱ两组患者的LVMI（142.02±30.79）、（138.23±32.19）g/m2较正常对照组（82.48±25.24）g/m2增大（P〈0.0001）,血压增高,而DIRH（5.63±2.15）%、（6.15±2.58）%较对照组（13.19±2.72）%显著减小（P〈0.0001）,DING、年龄、血脂、血糖差异无统计学意义。Ⅰ、Ⅱ两组参数间差异无统计学意义（P〉0.05）。治疗后Ⅰ组患者的LVMI减小（142.02±30.79）g/m2VS（87.23±16.26）g/m2（P〈0.0001）,DIRH增大（5.63±2.15）%VS（12.86±2.48）%（P〈0.0001）,而Ⅱ组LVMI、DIRH无显著性改变;两组患者的血压下降至正常。Ⅰ、Ⅱ两组相比,前者的左室重量指数变化率（LVMICH）、DIRH及其变化率（DIRHCH）较后者显著增大（P〈0.05）;血压、血糖、血脂差异无统计学意义。治疗前后血脂、血糖无显著变化。相关分析表明：患者治疗前的LVMI与DIRH之间、LVMICH与DIRHCH间均呈良好相关性（r=-0.59;0.7 1,P〈0.0001）。结论高血压病患者左室重量增加与内皮功能障碍相关,辛发他汀可以抑制患者左室重量增加并同时显著改善内皮功能。     

辛伐他汀对老年急性心肌梗死的冠脉介入治疗的心肌保护作用

目的探讨辛伐他汀对老年急性心肌梗死患者经皮冠状动脉介入治疗（PCI）后心肌损伤及预后影响。方法将我院2009年2月～8月收治的116例急性心肌梗死患者随机分成对照组和实验组,实验组于PCI前2小时顿服辛伐他汀80mg,对照组及实验组术后均口服辛伐他汀40mg/qd。观察院内实验室检查结果和术后30天主要心脏不良事件的发生率。结果 PCI术后2组心肌损伤及炎性标志物均有不同程度升高,但实验组术后24小时CK-MB、TNT-HSST、hs-CRP均显著低于对照组（P〈0.05）,术前与术后8小时两组CK-MB水平无显著性差异（P〉0.05）。实验组主要不良心脏事件（major adverse cardiovascular events,MACE）发生率低于对照组（4.0%vs18.1%,P=0.044）。实验组、对照组服药后30天两组均有谷丙转氨酶轻度升高,两组间无显著性差异（P〉0.05）。结论对于行PCI治疗的老年AMI患者术前短期辛伐他汀负荷剂量能减少PCI对急性心肌梗死患者造成的心肌损伤及炎症反应,降低PCI术后不良心脏事件的发生,且安全性良好。     

The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia

The aim of this study was to assess the strength of hemostatic effects of ezetimibe, administered alone or in combination with simvastatin, in patients with isolated hypercholesterolemia. One hundred and four patients with isolated primary hypercholesterolemia were randomized to one of four treatment groups, simultaneously treated for 90 days with ezetimibe (10 mg daily), simvastatin (40 mg daily), ezetimibe (10 mg daily) plus simvastatin (40 mg daily), or placebo. Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of randomization and after 30 and 90 days of therapy. Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe, only simvastatin reduced plasma levels/activity of fibrinogen, factor VII, factor X, von Willebrand factor, and plasminogen activator inhibitor-1. The strongest effects on plasma lipids/lipoproteins and the assessed hemostatic variables were observed when patients were treated with both simvastatin and ezetimibe. With the exception of oxidized low-density lipoproteins, the hemostatic effects of simvastatin or simvastatin plus ezetimibe did not correlate with the changes in plasma lipids/lipoproteins. Our study shows that simvastatin is a more effective agent than ezetimibe in affecting coagulation and fibrinolysis in individuals with isolated hypercholesterolemia. It also suggests that the combined administration of simvastatin and ezetimibe may bring more benefits to patients than monotherapy with only one of these agents.     

辛伐他汀相关肌酸激酶升高和肝功能异常

1例88岁男性患者,因急性冠脉综合征联合使用氯吡格雷、阿司匹林、酒石酸美托洛尔、替米沙坦、辛伐他汀、达肝素钠、硝酸甘油。第5天辛伐他汀剂量由20mg,每晚1次增至40mg,每晚1次。第8天停用替米沙坦,给予口服地尔硫革15mg,3次／d和苯磺酸氨氯地平。第42天患者出现骨骼肌极度乏力伴肌痛。实验室检查：肌酸激酶（CK）8100U／L,肌酸激酶同工酶305U／L,肌钙蛋白0．046斗g／L,丙氨酸转氨酶（ALT）102U／L,天冬氨酸转氨酶（AST）151U／L。停用辛伐他汀并静脉滴注硫普罗宁。停药第16天复查血生化：CK55U／L,ALT13U／L,AST14U／L。8天后再次联合应用辛伐他汀10mg,每晚1次与地尔硫革30mg,3次／d,应用22天未见CK和肝功能异常。     

辛伐他汀对高胆固醇血症患者大动脉僵硬度的影响

目的观察辛伐他汀(降血脂药)对未合并冠心病的高胆固醇血症患者动脉僵硬度的影响。方法 51例高胆固醇血症患者应用辛伐他汀20 mg.d-1治疗12周,分别在0,12周测定患者的代谢指标、肱踝脉搏波传导速度(baPWV)。结果辛伐他汀治疗后,患者血浆总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平均明显降低((P<0.01,P<0.05);与治疗前相比,双侧baPWV水平均显著降低(双侧均P<0.01)。结论辛伐他汀可改善无明确冠心病的高胆固醇血症患者动脉血管硬化程度。     

老年高血压患者C反应蛋白水平与颈动脉内中膜厚度相关性及辛伐他汀的干预研究

目的研究老年高血压患者C反应蛋白水平与颈动脉内中膜厚度相关性及辛伐他汀的干预作用。方法入选200例老年高血压患者,随机分为三组:对照组(安慰剂)、辛伐他汀组(辛伐他汀20 mg,qn)、非洛贝特组(非洛贝特200 mg,bid),分别于服药前、服药后3个月和6个月检测血浆C反应蛋白水平、颈动脉内中膜厚度、血浆胆固醇及甘油三酯浓度,探讨不同程度颈动脉内中膜厚度患者的C反应蛋白水平。并且通过比较不同药物治疗前后的C反应蛋白水平与颈动脉内中膜厚度,研究辛伐他汀对老年高血压患者动脉粥样硬化的干预作用。结果老年高血压患者随着颈动脉内中膜厚度的增加,C反应蛋白水平相应升高。应用辛伐他汀可降低老年高血压患者的C反应蛋白水平和颈动脉内中膜厚度,结果表明辛伐他汀能够有效控制老年高血压患者动脉粥样硬化程度,抑制动脉粥样硬化炎症反应。结论对于老年高血压患者,C反应蛋白水平与颈动脉内中膜厚度具有明显相关性,可以作为评价动脉粥样硬化程度的简便指标进行推广。而辛伐他汀可明显抑制动脉粥样硬化炎症反应,降低老年高血压患者的动脉粥样硬化水平。     

254例糖尿病周围神经病变中医辨证分型及相关性研究

目的研究糖尿病周围神经病变患者的中医辨证分型与体重指数等指标的相关性。方法本研究共收集254例糖尿病患者的临床资料,依据糖尿病周围神经病变诊断标准分为有DPN组和无DPN组,再将DPN组患者按照2007版《糖尿病中医防治指南》糖尿病性周围神经病变辨证分型标准辨证分为4种证型:痰瘀内阻证、阴虚血瘀证、气虚血瘀证、肝肾亏虚证,对相关资料进行分型。结果 DPN组中阴虚血瘀型患者所占比例高于其他3个证型。气虚血瘀证和肝肾亏虚证的病程较阴虚血瘀证、痰瘀内阻证长。气虚血瘀证、肝肾亏虚证、痰瘀内阻证的体重指数和收缩压与阴虚血瘀证比较,差异均有统计学意义(P<0.05)。痰瘀内阻证的糖化血红蛋白、总胆固醇、低密度脂蛋白和空腹C肽较其他3证为高,差异有统计学意义(P<0.05)。气虚血瘀证、肝肾亏虚证的餐后2hC肽值与其他证型比较,差异有统计学意义(P<0.05)。结论阴虚血瘀是导致糖尿病周围神经病变发生的重要中医病机。阴虚血瘀型糖尿病周围神经病变患者相较于其他证型的糖尿病周围神经病变患者有体形相对消瘦、血压相对较低的特点。阴虚血瘀证和痰瘀内阻证病程较短,气虚血瘀证和肝肾亏虚证病程较长。     

Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats

Introduction

Statins and β1-adrenergic antagonists are well established in cardiovascular events therapy and prevention. The previous study showed that statins might impact on β-adrenergic signalling and blood pressure in a dose-dependent manner. The aim of the study was to evaluate the impact of 4-week administration of simvastatin given at different doses on the heart rate and blood pressure after injection of metoprolol in rats.

Material and methods

The experiments were performed in normocholesterolaemic and normotensive Wistar rats. Rats received simvastatin in doses of 1, 10 and 20 mg/kg body weight (bw) for 4 weeks. The control group received 0.2% methylcellulose. For the further estimation of the heart rate and blood pressure, metoprolol at 5 mg/kg bw or 0.9% NaCl was injected intraperitoneally.

Results

Simvastatin at doses of 1, 10 and 20 mg/kg bw did not influence the heart rate or blood pressure as compared to the control group. Metoprolol injection statistically significantly decreased the heart rate (439.29±14.03 min⁻¹ vs. 374.41±13.32 min⁻¹; p<0.05). In rats receiving simvastatin during the 4-week period after metoprolol injection, heart rate and blood pressure (mean, systolic, diastolic) were similar as compared to the group receiving metoprolol alone.

Conclusions

Simvastatin administration during a 4-week period in different doses did not influence the heart rate or blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats.     

Lactone form 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway

Kim IS, Jeong BC, Kim OS, Kim YJ, Lee SE, Lee KN, Koh JT, Chung HJ. Lactone form 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway. J Periodont Res 2011; 46: 204–213. © 2010 John Wiley & Sons A/S Background and Objective: Recent studies reported that the lactone forms of 3‐hydroxy‐ 3‐methylglutaryl‐coenzyme A reductase inhibitors, which are also known as statins, have a bone stimulatory effect. However, there are few reports on the effect of statins on periodontal ligament cells. This study examined the statin‐induced osteoblastic differentiation of mouse periodontal ligament cells as well as its mechanism. Material and Methods: Mouse periodontal ligament cells were cultured with lovastatin or simvastatin, and their viability was measured. The levels of alkaline phosphatase (ALP), osteocalcin, bone sialoprotein and bone morphogenetic protein‐2 mRNA expression were evaluated by RT‐PCR. The osteoblastic differentiation was characterized by the ALP activity and Alizarin Red‐S staining for calcium deposition. The activity of the osteocalcin gene (OG2) and synthetic osteoblast‐specific elements (6×OSE) promoter with statins was also measured using a luciferase assay. For the signal mechanism of statins, the ERK1/2 MAPK activity was determined by western blot analysis. Results: A statin treatment at concentrations < 1 μm did not affect the cell viability. Lovastatin or simvastatin at 0.1 μm increased the levels of ALP, osteocalcin, bone sialoprotein and bone morphogenetic protein‐2 mRNA in mouse periodontal ligament cells. In addition, the ALP activity, mineralized nodule formation and OG2 and OSE promoter activity were higher in the lovastatin‐ or simvastatin‐treated cells than the control cells. Western blot analysis confirmed that the statins stimulated the phosphorylation of ERK1/2. Conclusion: Lovastatin and simvastatin may stimulate the osteoblastic differentiation of periodontal ligament cells via the ERK1/2 pathway. This suggests that the statins may be useful for regenerating periodontal hard tissue.