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。     

辛伐他汀对大鼠肾小管上皮细胞转分化的作用

目的:观察辛伐他汀对实验性1型糖尿病大鼠肾小管上皮细胞转分化的作用。方法:将实验动物随机分为对照组、糖尿病组及治疗组。治疗组给予辛伐他汀[5 mg/(kg.d)]治疗12周。于实验第6,9,12周检测24 h尿蛋白(24 h TP),12周检测血清肌酐(Scr),内生肌酐清除率(Ccr)和NAG酶。采用免疫组织化学技术检测各组肾小管间质中-αSMA,MCP-1,CD44表达水平。结果:糖尿病大鼠肾组织中-αSMA,MCP-1和CD44表达较对照组明显增加(P<0.01),治疗12周后,辛伐他汀可明显降低1型糖尿病肾病大鼠肾小管间质中-αSMA,MCP-1和CD44表达(P<0.01),并降低蛋白尿(P<0.01),改善肾功能各指标及肾组织病理学损害。-αSMA表达分别与MCP-1,CD44表达及24 hTP呈正相关(r=0.998 5,0.976 3,1.000 0,P<0.01)。结论:辛伐他汀对糖尿病肾小管间质病变具有保护作用,其机制至少部分与抑制肾小管上皮细胞转分化,下调肾小管间质中-αSMA,MCP-1和CD44表达有关。     

银杏叶提取物对动脉粥样硬化大鼠斑块及血脂水平影响

目的:研究银杏叶提取物是否具有延缓大鼠斑块进程、调节动脉粥样大鼠血脂水平的作用。方法:建立动脉粥样硬化大鼠模型36只,分为3组:银杏叶提取物组、辛伐他汀组、高脂未干预组,每组12只。干预4周后分别处死大鼠,取血样进行血脂水平分析;对大鼠主动脉病理切片进行形态学比较。采用Stata6.0统计软件分析:①血清学指标、相对光密度值采用x軃±s表示;②两组间比较采用t检验;以P<0.05为差异有显著性,均为双侧检验。结果:银杏叶提取物组和辛伐他汀组脂蛋白水平:TC、TG、LDL-C、ox-LDL均明显低于高脂未干预组(P<0.01),但前两者之间也有统计学差异:银杏叶提取物组血脂水平要高于辛伐他汀组(P<0.05);经银杏叶提取物和辛伐他汀干预组斑块进展明显慢于高脂未干预组。结论:银杏叶提取物具有调节动脉粥样硬化大鼠血脂水平,保护血管内皮、延缓动脉粥样硬化斑块进展的作用,但是其作用要弱于辛伐他汀。     

尼莫地平联合辛伐他汀防治自发性蛛网膜下腔出血后脑血管痉挛

目的:探讨尼莫地平联合辛伐他汀防治自发性蛛网膜下腔出血(SAH)后血管痉挛(CVS)的临床疗效及安全性。方法:83例SAH患者随机分为对照组41例和观察组42例。2组患者在给予SAH常规治疗的基础上,对照组给予尼莫地平治疗,观察组给予尼莫地平联合辛伐他汀治疗,疗程均为4周。比较2组疗效、CVS及其他不良事件的发生率。结果:治疗后,观察组患者的痊愈率(45.2%)明显高于对照组(24.4%),CVS的发生率(9.5%)低于对照组(26.8%),不良事件发生率(9.5%)低于对照组(39.0%),Hunt-Hess分级为I级、II级的患者数量明显多于对照组(均P0.05)。结论:尼莫地平联合辛伐他汀治疗有助于降低SAH后CVS的发生率,降低不良反应,提高疗效。     

辛伐他汀对高肺血流并野百合碱注射大鼠肺动脉高压模型的影响

目的 观察辛伐他汀对高肺血流并野百合碱注射大鼠肺动脉高压模型的影响.方法 采用腹主动脉-下腔静脉造瘘联合野百合碱注射制作肺动脉高压动物模型.40只大鼠随机平均分为安慰剂组、辛伐他汀A组[1 mg/(kg·d)]、辛伐他汀B组[2 mg/(kg·d)]和正常对照组.造瘘术后第37d各组分别测量平均肺动脉压力(mPAP)和右心室肥厚程度[RV/(LV S)],观察肺小动脉血管厚度,比较无肌性动脉肌化程度,比较血清总胆固醇(CHOL)浓度.结果 同正常对照组相比,安慰剂组大鼠的mPAP[(24.6±3.2) vs (13.9±1.4) mmHg,1 mmHg=0.133 kPa]、RV/(LV S)[(0.456±0.071) vs (0.245±0.026)]升高(P＜0.05),肺小动脉血管厚度增加[(28.64±5.95)% vs (9.36±2.24)%,P＜0.05],无肌性血管肌化百分比增加[(66.25±9.32)% vs (17.67±3.62)%,P＜0.05)].辛伐他汀治疗减轻了安慰剂组各项指标的增加(P＜0.05).各组间血清CHOL浓度差异无统计学意义.结论 辛伐他汀通过抑制大鼠肺小血管重构,减轻肺动脉高压的形成,提示辛伐他汀可能对左向右分流型先心病具有一定的治疗前景.     

辛伐他汀与阿司匹林联合用药对高血压病患者颈动脉粥样硬化的干预作用

目的探讨高血压病患者在降血压治疗的同时,辛伐他汀和肠溶阿司匹林联合用药对颈动脉粥样硬化和心、脑血管事件的干预作用。方法选择162例高血压病合并颈动脉粥样硬化患者,将其随机分为药物联合干预组和对照组:干预组82例,在降血压治疗的同时应用辛伐他汀(每晚20mg)和肠溶阿司匹林(75mg/d)。对照组80例,仅给予降血压治疗。共随访3年,分别在干预前及干预后第1、2、3年检测颈动脉内-中膜厚度、颈动脉内径、颈动脉内-中膜厚度/颈动脉内径的比值、颈动脉斑块积分及血压、血脂、血小板聚集率和血浆纤维蛋白原等指标。结果干预组在随访后第1年平均颈动脉内-中膜厚度和斑块积分分别为(1.01±0.12)mm、3.8±2.5,与干预前比较差异无显著性(P>0.05),第2、3年分别为(0.80±0.16)mm、2.6±1.6;(0.80±0.20)mm、2.5±1.2,与干预前比较明显降低(P<0.01)。颈动脉内-中膜厚度/内径比值在干预后也明显降低。随访结束时,干预组心、脑血管病的发生率分别为10.90%和4.87%,与对照组相比明显降低(P<0.05)。结论在有效降血压的同时,给予辛伐他汀和肠溶阿司匹林联合用药,能延缓和逆转高血压病患者颈动脉粥样硬化的进展,对心、脑血管事件的发生有很好的预防作用。     

辛伐他汀对急性冠脉综合征患者血清C-反应蛋白的影响

目的观察急性冠脉综合征(ACS)患者早期应用辛伐他汀治疗对血脂和炎症反应标记物的影响及差异,探讨他汀类药物在ACS早期治疗中的作用。方法 ACS住院患者113例,入院后测定血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白介素-6(IL-6)和C反应蛋白 (CRP)水平,然后随机分为辛伐他汀治疗组和对照组。出院时重复测定上述指标。同期测定30例健康者作对照比较。结果治疗组治疗后CRP、IL-6比治疗前明显下降,差异有显著性意义(P<0．05)。结论 ACS患者早期应用辛伐他汀治疗有明显的抗感染作用。