辛伐他汀辅助治疗特发性肺纤维化的随机对照研究

目的观察口服辛伐他汀对特发性肺纤维化的辅助治疗效果。方法前瞻性对照试验,依标准纳入60名患者,随机分为两组。常规组采用24个月的常规治疗方案:泼尼松联合N-乙酰半胱氨酸和硫唑嘌呤治疗。辛伐他汀组在采用标准方案的基础上口服辛伐他汀20 mg/d。记录两组患者治疗前和治疗3、6、12、18、24、30、36个月的最大肺活量占预测值百分比(FVC%pred)、一氧化碳弥散量占预测值百分比(DLCO/VA%pred)、第一秒用力呼气容积占预测值百分比(FEV1%pred)、6min步行距离、动脉血氧分压(Pa O2),治疗前以及治疗后6、12个月的HRCT的影像学表现,并监测治疗期间不良反应。结果完成试验的患者常规组有29名,辛伐他汀组有24名。辛伐他汀组FVC%pred仅在治疗第9个月时(80.11±9.23)%高于常规组(74.72±6.34)%,P0.01,其余时间两组无统计学差异;辛伐他汀组DLCO/VA%pred在治疗第12、21、30、36个月时高于常规组,P0.05;两组的FEV1%pred没有统计学差异;辛伐他汀组6min步行距离在治疗第9~33个月时高于常规组,P0.05;辛伐他汀组Pa O2在治疗第6~18个月时高于常规组,P0.05;两组的HRCT影像学表现没有统计学差异,辛伐他汀组36个月存活率(62.5%)高于常规组(34.5%),生存分析两组有统计学差异(P=0.012)。结论口服辛伐他汀不能逆转肺纤维化过程,但能改善肺纤维化患者的肺功能参数和气体交换,提高生活质量,短期内有助于延长患者生命。     

辛伐他汀对人网膜前脂肪细胞细胞周期及caspase-3表达的影响

目的：观察辛伐他汀对人网膜前脂肪细胞细胞周期和caspase-3表达的影响。方法：分离、培养、鉴定人网膜前脂肪细胞,用不同浓度的辛伐他汀干预人网膜前脂肪细胞,MTT法测定细胞增殖,流式细胞仪测定细胞周期,免疫细胞化学法测定caspase-3的表达。结果：实验分离出的人网膜前脂肪细胞经诱导16d后分化为多脂滴的成熟脂肪细胞,10-4mol/L辛伐他汀对人网膜前脂肪细胞的增殖有显著地抑制作用,细胞周期测定显示细胞被阻滞在G0/G1期,且干预后人网膜前脂肪细胞caspase-3表达阳性率显著增加。结论：辛伐他汀可以通过阻滞细胞周期抑制人网膜前脂肪细胞增殖,可能通过增加caspase-3的表达诱导细胞凋亡。     

辛化他汀对原发性高血压心肌纤维化的影响

目的：观察辛化他汀对原发性高血压(EH)心肌纤维化的影响。方法：将60例EH患者随机分为2组：A组28例,单用贝那普利（10mg/d）,B组32例,等量贝那普利加辛化他汀（20mg/d）。应用放射免疫分析技术检测Ⅲ型前胶原末端肽（PⅢP）,Ⅳ型前胶原末端肽（PⅣP）及转化生长因子（ TGFβ1）含量。采用多普勒超声心动图仪测定左室结构及舒缩功能变化。结果：2组患者治疗6个月后,平均动脉压,PⅢP,PⅣP,TGFβ1及室间隔舒张末期厚度,左室后壁厚度指数均较治疗前下降;2组治疗后二尖瓣血流舒张早期流速（VE）和心房收缩期流速（VA）之比均有上升（P<0.01）,而B组上升更明显（P<0.05）,左室收缩功能指标治疗前后无明显变化;2组比较PⅢP,PⅣP,TGFβ1下降和左室舒张功能改善以B组更明显（P<0.05或P<0.01）。结论：EH患者在接受血管紧张素转换酶抑制药同时,再联合使用辛化他汀,能明显减轻心肌纤维化程度,改善左室肥厚和舒张功能。     

辛伐他汀预防合并糖尿病的老年急性心肌梗死再发的疗效及可能机制

目的：探讨辛伐他汀对预防合并糖尿病的老年急性心肌梗死再发的疗效并分析可能机制,以期为临床诊疗提供参考。方法：分析2012年1月-2014年1月在某院通过保守治疗临床治愈的老年急性心肌梗死患者的临床资料,所有患者均合并2型糖尿病,依据患者心肌梗死愈后治疗药物不同分为观察组（辛伐他汀）及对照组。治疗随访1年后分析疗效及可能机制。结果：本研究共纳入患者92例,其中观察组49例,对照组43例。治疗后观察组患者TC、TG及LDL-C水平均显著低于对照组,差异具有统计学意义（P<0.05）;而HDL-C水平显著高于对照组（P<0.05）。观察组NO水平及FMD显著高于对照组,而ET-1水平显著低于对照组,差异均具有统计学意义（P<0.05）观察组患者CRP及IL-6水平均显著低于对照组,差异具有统计学意义（P<0.05）。观察组累积1年心肌梗死再发率显著低于对照组,差异具有统计学意义（8.16%,4/49 vs. 25.58%,11/43;Log-rank X²=4.954,P=0.026）。结论：辛伐他汀可有效预防合并糖尿的老年急性心肌梗死再发,可能与其调节血脂、血管功能及炎症反应有关。     

Metformin exacerbates and simvastatin attenuates myelin damage in high fat diet‐fed C57BL/6 J mice

Diabetic neuropathy is one of the most deleterious complications of diabetes mellitus in humans. High fat diet (HFD)‐fed C57BL/6 J mice are a widely used animal model for type 2 diabetes mellitus and metabolic syndrome. We investigated the effects of metformin and simvastatin on the ultrastructural characteristics of sciatic nerve fibers in these mice. Metformin treatment increased the number of structural defects of the myelin sheet surrounding these fibers in already affected nerves of HFD fed mice, and simvastatin treatment reduced these numbers to the levels seen in control mice. These results warrant further research on the effects of metformin and statins in patients developing diabetic neuropathy and advise caution when deciding about optimal treatment modalities in these patients.     

Effect of statins on blood pressure: Analysis on adverse events released by FDA

Objective: As a class of cholesterol-lowering drugs, statins have been reported to cause unexpected decrease in blood pressure (BP). However, most studies in this issue were subject to inadequate study design or very small sample size. The present study was designed to examine the BP-lowering effect of various statins. Methods: Here we retrieved 5.9 million clinical reports submitted to FDA Adverse Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to estimate the overall reporting odds ratio (ROR) of hypotension adverse events concurrent with various statins (i.e., atorvastatin, simvastatin, and rosuvastatin). Results: Comparing the reporting rate of hypotension event between statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p-value = 8.60 × 10^?4) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16 × 10^?45) were significantly associated with reduction in BP. On the other hand, the association between rosuvastatin and hypotension was observed to be nonsignificant (adjusted p-value = 0.65). Conclusion: To our knowledge, this is the first pooled analysis on large-scale data of adverse events to identify the BP-lowering effect of statins. The results will contribute to the development of novel statin-based antihypertensive therapies. In addition, the differential effects of individual statins can warrant subsequent research on the underlying mechanisms of BP control.     

辛伐他汀联合运动训练对慢性阻塞性肺疾病稳定期合并代谢综合征患者临床观察

目的:观察辛伐他汀联合运动训练对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期合并代谢综合征患者作用。方法:选取120例COPD稳定期合并代谢综合征(metabolism syndrome,MS)为研究对象,随机分为治疗A组、治疗B组及对照组各40例。治疗A组在常规治疗基础上加用辛伐他汀联合运动训练,治疗B组在常规治疗基础上加用辛伐他汀,对照组仅给予常规治疗,观察期为6个月。比较3组患者血清细胞因子白细胞介质(interleukin,IL)-6、IL-8与肿瘤坏死因子-α(tumor necrosis factor,TNF-α),胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA),脉搏波速度(pulse wave velocity,PWV),mMRC及6 min步行距离(6 minutes walking distance ,6MWD),并对所获结果进行统计学分析。结果:6个月治疗后:(1)治疗A组及治疗B组的血炎症因子IL-6、IL-8与TNF-α较治疗前及对照组均明显下降,差异有统计学意义(P<0.01);治疗组2组之间比较,A组较B组有明显下降,差异有统计学意义(P<0.05);(2)治疗A组与治疗B组、对照组比较,HOMA有明显下降,差异有统计学意义(P<0.05),但治疗B组与对照组比较,无明显差异(P>0.05);(3)治疗A组、B组与对照组比较,PWV值有明显下降,差异有统计学意义(P<0.05);治疗组2组之间比较,A组较B组PWV值下降,但无明显差异(P>0.05);(4)治疗A组与治疗B组、对照组比较,mMRC及6MWD均明显改善,差异有统计学意义(P<0.05);治疗B组较对照组比较,mMRC及6MWD均明显改善,差异有统计学意义(P<0.05)。结论:辛伐他汀联合运动训练能降低COPD稳定期合并MS的 IL-6、IL-8、TNF-α水平;改善胰岛素抵抗及大动脉弹性,并改善患者呼吸困难程度及运动能力。     

Effect of simvastatin treatment on plasma visfatin levels in obese women

Aims: Obesity is one of the major concerns in the world currently, its prejudicial effect is exerted by proteins secreted by adipose tissue, among them visfatin was demonstrated to be related with BMI and cardiovascular diseases. The HMG-CoA reductase inhibitors are known to minimize the cardiovascular risk in hyperlipidemic patients and recently the discovery of various pleiotropic effects has made the statins evidencing among others anti-inflammatory effect. Our objective in this study was to determinate if simvastatin treatment may modulate visfatin levels in obese women without any other metabolic disorder.

Methods: We recruited 25 obese women without any other metabolic disorder and treated with simvastatin for 6 weeks 20?mg/day.

Results: The levels of plasma visfatin were similar before and after treatment (22?±?20 versus 27?±?14?ng/mL, p?>?0.05) and correlated with BMI before treatment (p?=?0.001). We also found correlations among visfatin and insulin levels (p?=?0.015) and HOMA-IR (p?=?0.025) only after treatment.

Conclusion: These findings suggest that visfatin is not modulated by simvastatin treatment in this group but the treatment may interfere on the relation among visfatin, BMI, insulin and HOMA-IR.     

辛伐他汀预处理对脓毒症大鼠血清血管性血友病因子的影响

目的 评价辛伐他汀预处理对脓毒症大鼠血管内皮细胞功能的影响.方法 清洁级雌性Wistar大鼠96只,体质量200～250 g,4月龄.采用随机数字表法,将大鼠随机分为3组:假手术组32只、脓毒症组32只和辛伐他汀组32只.脓毒症组和辛伐他汀组采用盲肠结扎穿孔法制备脓毒症模型.辛伐他汀组制模前胃内灌注辛伐他汀20 mg·kg-1 ·d-1,每日l次,连续2周;假手术组和脓毒症组胃内灌注等容量生理盐水.分别于术后3、6、24和48小时取8只大鼠,采集颈动脉血样,测定白细胞计数;采用酶联免疫吸附测定(ELISA)法检测血清血管性血友病因子(vWF)水平;记录术后3小时内、＞3～6小时、＞6～24小时和＞24～48小时各时段大鼠的死亡情况.结果 与假手术组比较,脓毒症组和辛伐他汀组术后各时点白细胞计数和血清vWF浓度升高,术后6小时达峰值,白细胞计数分别为(7.45±0.69)×109/L,(12.79±0.51)×109/L,(10.36±0.19)×109/L; vWF水平分别为(0.543±0.001)μg/L,(1.198±0.035)μg/L,(1.018±0.005)μg/L( P＜0.05);与脓毒症组比较,辛伐他汀组术后各时点白细胞计数和血清vWF水平降低,术后24～48小时内病死率降低(脓毒症组75.0％,辛伐他汀组50.0％)(P＜0.05).结论 辛伐他汀可保护脓毒症大鼠的内皮细胞功能,从而降低48小时内的病死率.