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.     

Selective benefits of simvastatin in bitransgenic APPSwe,Ind/TGF-β1 mice

Cognitive and cerebrovascular deficits are 2 landmarks of Alzheimer's disease (AD) to target for effective therapy. Here, we evaluated the efficacy of simvastatin in bitransgenic A/T mice overexpressing a mutated form of the human amyloid precursor protein (APP_Swe,Ind) and a constitutively active form of transforming growth factor-β1. These mice feature the AD amyloid beta (Aβ) and cerebrovascular pathology. Simvastatin significantly decreased insoluble Aβ peptide levels and Aβ plaque load despite no effect on β-site amyloid precursor protein-cleaving enzyme and Aβ-degrading enzyme neprilysin protein levels. However, simvastatin failed to improve spatial learning and memory deficits and the decreased baseline levels of the memory-related protein early growth response-1 (Egr-1) in the hippocampus CA1 area. The impaired hyperemic response to whisker stimulation in A/T mice was not improved with treatment, but simvastatin fully restored constitutive nitric oxide synthesis in vessel walls and exacerbated agonist-mediated dilatory deficits. These findings point to the efficacy of simvastatin on selective AD features in a complex model of the disease, likely reflecting the challenges faced by recent clinical trials in assessing statin efficacy.     

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。     

阿仑磷酸钠和辛伐他汀对体外培养成骨细胞的影响

目的探讨辛伐他汀和阿仑磷酸钠对体外培养成骨细胞的影响。方法分离3周龄成骨细胞，体外培养时以辛伐他汀和阿仑磷酸钠刺激，观察成骨细胞碱性磷酸酶水平和成骨细胞增殖率。结果辛伐他汀、阿仑磷酸钠可以促进成骨细胞增殖，增加碱性磷酸酶的分泌，二者共同作用后作用更显著。结论辛伐他汀和阿仑磷酸钠能促进成骨细胞增殖和分泌碱性磷酸酶，可以联合作用促进骨形成。     

辛伐他汀口腔崩解片的人体生物等效性研究

目的:比较2种辛伐他汀制剂的人体生物等效性。方法:18名健康男性志愿者随机交叉单剂量口服辛伐他汀口腔崩解片(受试制剂)与辛伐他汀片(参比制剂)40mg,用液-质联用法测定人血浆中药物浓度,并用3p97软件计算药动学参数和生物利用度。结果:2种辛伐他汀制剂在人体内药-时曲线符合一室模型,受试制剂与参比制剂的Cmax分别为(6.73±5.22)、(7.08±5.41)ng·mL-1,tmax分别为(2.11±0.74)、(1.89±0.85)h,AUC0～12分别为(19.83±19.09)、(19.98±18.20)ng·h·mL-1,AUC0～∞分别为(22.18±20.09)、(22.41±21.07)ng·h·mL-1。受试制剂相对于参比制剂的生物利用度为(99.25±13.11)%。结论:2种辛伐他汀制剂具有生物等效性。     

拜糖平联合舒降之及减轻体重对中青年2型糖尿病胰岛素抵抗的相关研究

目的观察拜糖平联合舒降之对中青年2型糖尿病(T2DM)的疗效及对胰岛素抵抗(IR)的影响。方法对60例服用拜糖平和舒降之的中青年T2DM患者,采用WHO推荐方法进行葡萄糖耐量试验(OGTT),分别测定中青年T2DM患者的空腹血糖(FPG)与空腹胰岛素(FIN),将它们乘积的倒数作为(ISI)IR的指标,计算其曲线下面积AUC(FPG)和AUC(FIN),并记录血脂、血压、身高体重指数。结果经治疗后后糖尿病患者血糖、血脂、血压、AUC(FGP)面积下降,ISI值上升,差异有显著性(P<0.05)。AUC(FIN)治疗前后差异无显著性,(P>0.05)。结论拜糖平联合舒降之不仅能明显改善血糖及血脂代谢状况,还能改善中青年T2DM患者的胰岛素抵抗,对于其余年龄段的患者作用有待进一步研究。     

辛伐他汀片人体药代动力学及相对生物利用度的研究

目的:评价2种辛伐他汀片的相对生物利用度和生物等效性.方法:选择18名健康受试者随机分为2组,先后予单剂量、交叉口服辛伐他汀受试制剂和参比制剂各40 mg,采用液相色谱-质谱-质谱联用法测定给药后不同时间受试者血浆中辛伐他汀的浓度,对辛伐他汀受试制剂和参比制剂进行生物等效性评价.结果:辛伐他汀受试制剂和参比制剂的主要药代动力学参数:cmax分别为(9.70±6.62)及(10.06±6.29) μg/L;tmax分别为(1.64±1.01)及(1.64±0.68)h;t1/2分别为(3.48±1.16)及(4.15±1.90)h;AUC0～14h分别为(29.96±16.28)及(32.78±18.53)μg·h·L-1;AUC0～∞分别为(31.49±16.65)及(36.39±21.71) μg·h·L-1.受试制剂的相对生物利用度为(97.79±26.63)%.结论:2种制剂具有生物等效性.     

辛伐他汀抑制心肌梗死后心肌细胞凋亡及改善心功能的实验研究

目的:观察辛伐他汀对心肌梗死后心肌细胞凋亡及心功能的影响.方法:结扎大鼠左冠状动脉前降支造成心肌梗死模型,实验组给予药物处理(辛伐他汀40 mg/kg),7天后,TUNEL法检测心肌组织中的凋亡心肌细胞,超声检测左心室功能参数,生化法检测血脂水平.结果:辛伐他汀组较心肌梗死组在梗死区、梗死周边区、远离梗死区凋亡心肌细胞显著减少(P＜0.05),左心室功能改善(P＜0.05),血脂水平没有显著性差异(P＞0.05).结论:辛伐他汀抑制心肌梗死后心肌细胞凋亡,改善心功能.