辛伐他汀逆转左室肥厚的作用与抑癌基因PTEN表达的关系

目的观察辛伐他汀逆转自发性高血压大鼠(SHR)左心室肥厚(LVH)的作用及其与抑癌基因第10号染色体缺失的张力蛋白同源区(PTEN)表达的关系。方法16只雄性8周龄SHR测量体重和收缩压后,随机分为SHR治疗组和SHR对照组,分别给予辛伐他汀和安慰剂灌胃治疗,性别、年龄、数量匹配的Wistar大鼠给予安慰剂治疗作为正常对照组,疗程10周,观察辛伐他汀对大鼠收缩压和左心室重量/体重比值(LVW/BW)的影响,采用逆转录聚合酶链式反应(RTPCR)和蛋白免疫印迹法(Westernblot)检测辛伐他汀对心肌组织PTEN表达的影响。结果(1)治疗前两组SHR收缩压无显著差异(P>0.05),均高于Wistar正常对照组大鼠(P<0.01);给予辛伐他汀后,SHR治疗组收缩压(217.3±8.5)mmHg较SHR对照组(220.8±9.9)mmHg略有降低,但无统计学意义(P>0.05),且两组SHR收缩压仍高于Wistar正常对照组大鼠(126.0±5.8)mmHg,差异非常显著(P<0.01)。(2)SHR对照组大鼠的LVM/BW(4.10±0.13)mg/g明显高于Wistar正常对照组(3.04±0.12)mg/g,并有统计学意义(P<0.01),而SHR辛伐他汀治疗组的LVM/BW(3.73±0.08)mg/g较SHR对照组明显下降(P<0.01)。(3)SHR对照组大鼠心肌组织PTEN的mRNA表达水平(0.36±0.04)低于Wistar正常对照组(0.87±0.05),差异非常显著(P<0.01),SHR治疗组大鼠的PTENmRNA表达水平(0.60±0.05)较SHR对照组显著升高,并有统计学意义(P<0.01)。(4)Wistar正常对照组、SHR对照组和SHR治疗组大鼠心肌组织PTEN蛋白表达水平分别为50.53±2.92、24.65±3.89和40.32±4.04,其中SHR对照组明显低于Wistar正常对照组(P<0.01),SHR治疗组则较SHR对照组显著升高(P<0.01)。结论辛伐他汀能够逆转SHR的LVH,其机制可能与PTEN表达水平增加有关。     

A comparative study of the in vitro antioxidant activity of statins

Background: Treatment of hypercholesterolemia with statins is remarkably effective in cardiovascular prevention. This has led to the hypothesis that these drugs may act on the atherosclerotic plaque by mechanism(s) independent of the reduction of serum cholesterol levels. The aim of this study was to assess the total antioxidant activity of the most prescribed statins: fluvastatin, atorvastatin, pravastatin and simvastatin. Methods: We measured the in vitro antioxidant activity of statins as their ability to antagonize the oxidation of -keto-γ-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Uric acid and Trolox were used as the reference antioxidants. Results: The scavenging capacity towards hydroxyl radicals was highest for simvastatin (3375±112 U/mg), a value 270.2% higher (P<0.0001) compared to uric acid (reference antioxidant vs. hydroxyl radicals, 1249±71 U/mg). Among the tested statins, fluvastatin exhibited the highest anti-peroxyl radical antioxidant capacity (8755±187 U/mg) which appeared 50% lower (P<0.0001) compared to Trolox (reference antioxidant vs. peroxyl radicals, 17 460±379 U/mg). Conclusions: All the statins tested have intrinsic antioxidant activity with both anti-hydroxyl and peroxyl radical activity. Simvastatin was the most effective as an anti-hydroxyl radical antioxidant and fluvastatin as an anti-peroxyl radical antioxidant.     

依折麦布联合辛伐他汀治疗2型糖尿病合并高脂血症的临床观察

目的：探讨依折麦布联合辛伐他汀治疗2型糖尿病合并高脂血症的临床效果。方法：从本院2013年2-12月收治的2型糖尿病合并高脂血症患者中随机选择60例进行研究,随机数字表法分为两组,分别给予常规治疗和依折麦布联合辛伐他汀治疗治疗。观察记录两组的治疗效果,并进行比较。结果：治疗前两组血脂情况经比较差异无统计学意义（P〉0.05）;治疗后,两组高密度脂蛋白（HDL-C）较之治疗前显著上升,总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL-C）则均出现显著下降的情况,经比较差异均有统计学意义（P〈0.05）;但观察组的变化幅度较之对照组更加明显,经比较差异有统计学意义（P〈0.05）。结论：依折麦布联合辛伐他汀治疗2型糖尿病合并高脂血症可以获得良好的效果。     

比较不同剂量辛伐他汀治疗老年冠心病高脂血症患者的效果

目的：观察不同剂量的阿托伐他汀治疗老年冠心病高脂血症的疗效及机制。方法：采集本院临床120例患者分为观察组和对照组,两组均进行基础治疗,对照组在此基础上给予辛伐他汀阿托伐他汀60 mg/d,1次/d,观察组给予辛伐他汀阿托伐他汀40 mg/d,1次/d。观察两组患者血脂水平。结果：给药后,两组血脂水平均出现明显降低,观察组效果更为显著,两组比较差异有统计学意义（P〈0.05）。观察组不良反应发生情况仅为15.00%,而对照组为66.66%,两组比较差异有统计学意义（P〈0.05）。结论：给予40 mg剂量的辛伐他汀是治疗老年患者的冠心病合并高脂血症的最为安全有效的常规临床剂量。     

Renin–angiotensin system inhibition is not associated with increased sudden cardiac death,cardiovascular mortality or all-cause mortality in patients with aortic stenosis

Background

Renin–angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS.

Methods

All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses.

Results

769 (41%) patients received RASI. During a median follow-up of 4.3 ± 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95%CI: 0.50–2.83], p = 0.694), cardiovascular (HR: 1.05 [95%CI: 0.62–1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95%CI: 0.55–1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040).

Conclusions

RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression.     

Enhanced osteogenic healing process of rat tooth sockets using a novel simvastatin-loaded injectable microsphere-hydrogel system

PurposeTo evaluate the effects of simvastatin in a new injectable microsphere hydrogel system on bone healing process of tooth sockets.Materials and methodsSimvastatin was loaded in poly (lactic-co-glycolic acid) (PLGA) microspheres using an emulsion process, and the drug-loaded PLGA microspheres were further entrapped in a gelatin hydrogel to form an injectable microsphere-hydrogel system. Simvastatin-free hydrogel and blank microspheres hydrogel were used as controls. A rat tooth extraction socket model was generated, and the simvastatin-loaded microsphere-hydrogel composite was injected in the defect area of a tooth socket. At 1, 2, 5, and 8 weeks after the surgery, all the animals were sacrificed and the mandibles were harvested. The samples were examined using X-ray, hematoxylin and eosin staining, and histological evaluations.ResultsFive weeks after the surgery, significantly more bone tissue was formed in the simvastatin-loaded hydrogel group than in the simvastatin-free hydrogel group and the blank microspheres hydrogel group as control (p < 0.05).ConclusionThe injectable simvastatin-loaded microsphere hydrogel promoted new bone formation in the tooth extraction socket after 5 weeks, and has a promising potential for bone repair and regeneration.     

辛伐他汀纳米粒对脓毒症致急性肺损伤小鼠肺组织iNOS/eNOS平衡的调节及对预后的影响

目的分析辛伐他汀纳米粒对脓毒症致急性肺损伤(ALI)小鼠肺组织诱导型一氧化氮合酶(i NOS)/内皮型一氧化氮合酶(e NOS)平衡及预后的影响。方法取45只健康雄性C57/BL6小鼠,随机分为假手术组(开腹,但不结扎穿孔)、模型组(经盲肠结扎穿孔术制备脓毒症小鼠模型)和干预组(脓毒症小鼠模型+尾静脉注射辛伐他汀纳米粒制剂),每组各15只。造模后24 h,通过苏木精-伊红染色观察三组小鼠病理形态学改变,采用免疫组织化学法测定三组小鼠肺组织中i NOS和e NOS表达水平,记录小鼠造模1周时的生存状况。结果经苏木精-伊红染色结果发现,假手术组小鼠肺组织无明显病理改变;模型组小鼠肺组织细胞排卵紊乱、局部肺组织完整性受破坏、肺泡间中隔增厚、肺泡腔缩小、肺间质弥漫性水肿、弥漫性中性粒细胞浸润;相比模型组,干预组小鼠肺组织中性粒细胞渗出明显减少、肺组织损伤程度较轻、肺泡完整性较好。模型组肺组织中i NOS表达水平明显高于假手术组,干预组i NOS表达水平明显低于模型组(P<0.01);模型组肺组织中e NOS表达水平明显低于假手术组,干预组e NOS表达水平明显高于模型组(P<0.01)。模型组造模1周时的生存率(6.67%)低于假手术组(93.33%),干预组生存率(66.67%)高于模型组,差异均有显著性(P<0.05)。结论辛伐他汀纳米粒可保护脓毒症致ALI小鼠肺组织损伤,调节i NOS/e NOS平衡,可能是脓毒症致ALI具有保护效应的潜在处理位点。     

辛伐他汀治疗急性脑梗死的疗效观察

目的 探讨辛伐他汀治疗急性脑梗死临床疗效.方法 观察123例经颅脑CT或MRI证实的急性脑梗死患者治疗前后临床神经功能缺损的变化,并与对照组进行比较.结果 辛伐他汀治疗急性脑梗死有良好效果,其中治愈30例(24.39%),显著进步59例(47.97%),进步27例(21.95%),总有效率94.31%.未发现明显不良反应.结论 辛伐他汀治疗急性脑梗死安全有效.     

厄贝沙坦联合辛伐他汀治疗糖尿病肾病的疗效观察

目的 比较厄贝沙坦和辛伐他汀单独及联合治疗糖尿病肾病（DN）的疗效。方法 92例DN患者,随机分为3纽,分别予厄贝沙坦、辛伐他汀或两药联用治疗12周。比较治疗前后尿蛋白、血压、血钾和血Cr等的变化。结果 上述两药均能有效降低DN的尿蛋白,联合治疗降尿蛋白作用更明显（P〈0．05）,治疗前后血钾、血压、血Cr和CCr无明显变化（P〉0．05）。结论 对于DN患者,厄贝沙坦与辛伐他汀联合治疗与单药相比,具有更强的降尿蛋白作用。     

不同剂量辛伐他汀对冠心病患者血脂及安全性的影响

目的　观察不同剂量辛伐他汀对冠心病患者血脂的临床疗效及安全性的影响。方法　 32例冠心病伴血脂增高的患者随机分为A、B两组 ,其中A组 19例 ,口服辛伐他汀 5mg/d ,B组 13例 ,口服辛伐他汀 2 0mg/d ,比较服药前及服药后 4、8周血脂变化 ,将A组没有控制到理想水平的患者 ,增加剂量 2 0mg/d ,继续口服 8周。结果　①两组对降低胆固醇 (TC)和低密度脂蛋白 (LDL -C)有显著性疗效 (P <0 0 5 ) ;B组对甘油三脂 (TG)可有效降低。②服药 8周后 ,B组有 76 9%患者TC、LDL -C下降到理想水平 ,比A组 36 8%有显著性疗效 (P =0 0 3)。③将A组未达到理想水平的 13例患者继续口服辛伐他汀 2 0mg/d ,8周后又有 5 3 8%的患者TC、LDL -C降到理想水平。④A组及B组用药前、后 8周查血糖、血尿素氮、血肌酐、ALT、AST和CK均无统计学差异。结论　对血脂增高的冠心病患者 ,口服辛伐他汀 5mg/d对TC和 (或 )LDL -C高的患者疗效好。对伴TG高的患者 2 0mg/d不仅显著性降低TC、LDL -C ,同时TG有显著性降低 ,HDL -C升高。辛伐他汀剂量的增加不会导致副作用的增加