血必净注射液联合依那普利、阿托伐他汀钙对高血压肾损害患者临床疗效及肾功能的影响

目的 探讨血必净注射液与马来酸依那普利片、阿托伐他汀钙片联合对高血压肾损害患者临床疗效及肾功能的影响。方法 选取2014年12月—2017年12月榆林市第二医院100例高血压肾损害患者为研究对象,根据入院单双号将入选者分为对照组和观察组,每组50例。对照组患者口服马来酸依那普利片10 mg/次,1次/d;阿托伐他汀钙片10 mg/次,1次/d。观察组患者在对照组治疗的基础上静脉滴注血必净注射液,将1.5 g加入到0.9%氯化钠溶液100 mL中,1次/d。两组均连续治疗6个月。观察两组患者的临床疗效,比较两组治疗前后的肾功能指标、D-二聚体（D-D）和炎性因子水平。结果 治疗后,观察组总有效率为92.00%,显著高于对照组的76.00%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组肌酐（Cr）、尿微量白蛋白与肌酐比值（ACR）、尿微量白蛋白（mAlb）及尿β₂-微球蛋白（β₂-MG）水平均显著降低（P<0.05）;且观察组肾功能指标水平显著低于对照组（P<0.05）。治疗后,两组患者的D-D、白细胞介素-6（IL-6）、超敏C反应蛋白（hs-CRP）和肿瘤坏死因子-α（TNF-α）水平均显著降低（P<0.05）;且观察组D-D及各炎性因子水平显著低于对照组（P<0.05）。结论 血必净注射液联合马来酸依那普利片和阿托伐他汀钙片治疗高血压肾损害患者可有效改善肾功能,抑制机体炎性反应,疗效安全显著,值得临床推广使用。     

Statins and cardiovascular outcomes in elderly and younger patients with coronary artery disease: a post hoc analysis of the GREACE study

Introduction

The effect of cardiovascular disease (CVD) prevention measures aimed at elderly patients requires further evidence. We investigated the effect of statin treatment (targeted to achieve guideline goals) on CVD outcomes in different age groups to determine whether statins are more beneficial in the elderly.

Material and methods

The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study (n = 1,600 patients with established coronary heart disease (CHD), mean follow-up 3 years) was the absolute and relative CVD event (a composite of death, myocardial infarction, revascularization, unstable angina, heart failure and stroke) risk reduction in age quartiles (each n = 200). Patients on “structured care” with atorvastatin (n = 800) followed up by the university clinic and treated to lipid goal were compared with the corresponding quartiles on “usual care” (n = 800) followed up by specialists or general practitioners of the patient''s choice outside the hospital.

Results

In the elderly (mean age 69 ±4 and 70 ±3 years in the “structured” and “usual care”, respectively) the absolute CVD event reduction between “structured” and “usual care” was 16.5% (p < 0.0001), while in the younger patients (mean age 51 ±3 years and 52 ±3 years in the “structured” and “usual care”, respectively) this was 8.5% (p = 0.016); relative risk reduction (RRR) 60% (p < 0.0001) vs. 42% respectively (p = 0.001). The elderly had higher rates of chronic kidney disease and higher uric acid levels, plus an increased prevalence of diabetes, metabolic syndrome and non-alcoholic fatty liver disease. These factors might contribute to the increased CVD risk in older patients.

Conclusions

All age groups benefited from statin treatment, but the elderly on “structured care” had a greater absolute and relative CVD risk reduction than the younger patients when compared with the corresponding patients assigned to “usual care”. These findings suggest that we should not deprive older patients of CVD prevention treatment and lipid target achievement.     

Clinical Efficacy of Subgingivally Delivered 1.2% Atorvastatin in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Atorvastatin (ATV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, statins have shown pleiotropic effects such as anti‐inflammation and bone stimulation. The aim of the present study is to investigate the effectiveness of 1.2% ATV as an adjunct to scaling and root planing (SRP) in the treatment of intrabony defects (IBDs). Methods: Sixty individuals were randomized into two treatment groups: SRP plus 1.2% ATV and SRP plus placebo gel. At baseline and 3, 6, and 9 months, clinical parameters, which included modified sulcus bleeding index, plaque index, probing depth (PD), and clinical attachment level (CAL), were recorded at baseline. Radiologic assessment of IBD fill was done using computer‐aided software at baseline and 6 and 9 months. Results: Mean PD reduction and mean CAL gain were greater in the ATV group than the placebo group at 3, 6, and 9 months. A significantly greater mean percentage of radiographic bone fill was found in the ATV group (35.49% ± 5.50%) compared to the placebo group (1.82% ± 1.32%) after 9 months. Conclusion: ATV as an adjunct to SRP can provide a new direction in the management of IBDs.     

阿托伐他汀通过ERK1/2通路抑制内皮微粒诱导的人脐静脉内皮细胞ICAM-1的表达

目的探讨阿托伐他汀对内皮细胞微粒(EMPs)诱导人脐静脉内皮细胞(HUVECs)细胞间黏附分子-1(ICAM-1)表达的影响及其与ERKl/2信号通路的关系。方法将HUVECs分为不同浓度EMPs作用组与阿托伐他汀干预组。应用Western印迹检测磷酸化ERK1/2和ICAM-1蛋白的表达,实时荧光定量PCR(qRT-PCR)检测ICAM-1 mRNA的表达。结果 EMPs可诱导HUVECs ICAM-1 mRNA和蛋白及磷酸化ERK1/2蛋白表达增加,且具有浓度和时间依赖关系(均P<0.01);阿托伐他汀及ERK1/2特异性抑制剂PD98059显著抑制EMPs诱导的HUVECs ICAM-1 mRNA和蛋白及磷酸化ERK1/2蛋白的表达(均P<0.01)。结论阿托伐他汀通过ERK1/2信号通路抑制EMPs诱导HUVECs ICAM-1表达。     

阿托伐他汀在大鼠颈总动脉球囊损伤模型中对NF-κB及其相关炎性因子的影响

目的研究阿托伐他汀在大鼠颈总动脉球囊损伤模型中对核转录因子NF-κB及其相关炎性因子:细胞间细胞黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)、单核细胞趋化蛋白1(MCP-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)的影响。方法健康雄性Wistar大鼠72只,体重300～350 g,随机分为3组,阿托伐他汀干预组为实验组,通过灌胃法给予阿托伐他汀[10 mg/(kg.d)];安慰剂对照组为模型组,给予等量清水;空白对照组为假手术组,只分离出左颈总动脉后缝合,不作球囊损伤处理,给予等量清水。药物干预3天后实验组与模型组行左侧颈总动脉内膜球囊损伤术,术后实验组继续每日给予阿托伐他汀,模型组及假手术组给予等量清水,每组中各有6只于术后1、3、7天和14天分别处死,采集血清及颈总动脉标本。采用组织形态学观察内膜增生,采用免疫组织化学及酶联免疫吸附试验检测NF-κB及ICAM-1、VCAM-1、MCP-1、IL-6、TNF-α等炎性因子的表达。结果阿托伐他汀组球囊损伤后内膜增生面积显著小于模型组(P<0.01);模型组血管壁及血清中NF-κB及炎性因子ICAM-1、VCAM-1、MCP-1、IL-6、TNF-α的表达显著高于假手术组;阿托伐他汀组血管壁及血清中NF-κB及炎性因子ICAM-1、VCAM-1、MCP-1、IL-6、TNF-α的表达显著低于模型组(P<0.01)。结论阿托伐他汀能抑制大鼠颈总动脉损伤后的内膜增生,其可能机制是通过特异性抑制炎症关键调节因子NF-κB,从而减少其下游炎性因子ICAM-1、VCAM-1、MCP-1、IL-6及TNF-α的表达而实现的。     

急诊PCI术前阿托伐他汀强化治疗对STEMI患者血清炎症因子的影响

目的：探讨术前给予80mg阿托伐他汀强化治疗对ST段抬高急性心肌梗死（STEMI）患者急诊介入治疗前后炎症反应的影响。方法：入选STEMI的患者95例,随机分为三组：A组（31例,术前给予负荷剂量阿托伐他汀80mg,术后给予阿托伐他汀40mg／d）;B组（34例,术前不服用他汀类药物,术后给予阿托伐他汀40mg／d）;c组（30例,术前不服用他汀类药物,术后给予常规剂量阿托伐他汀20mg／d）。分别于术前,术后24h、3d、7d测定各组血清高敏C反应蛋白（hsCRP）、血清淀粉样蛋白酶A（SAA）水平及术后肌酸激酶-同工酶（CK—MB）的峰值。结果：三组间术前血清hsCRP及SAA水平无明显差异;术后3d及7d,A组血清hsCRP及SAA水平明显低于B组、c组[7d：hsCRP（5．64±1．55）mg／L比（8．36±2．32）mg／L、（7．66±2．53）mg／L,SAA（7．31±3．61）mg／L比（10．13±5．13）mg／L、（12．86±4．98）mg／L,P〈0．051;而B组与C组间无显著差异（P〉0．05）。术后A组CK—MB峰值水平明显低于B、C组[（233．9±102．71）IU／L比（319．40±111．10）IU／L、（373．6±174．87）[U／L,P〈0．05],而B组与c组间无显著差异（P〉0．05）。A组在研究期间药物安全性与B、c两组比较亦无显著差异。结论：急诊PCI术前给予80mg阿托伐他汀强化治疗可显著降低ST段抬高急性心肌梗死患者血清炎性因子水平及肌酸激酶一同工酶峰值水平,且安全性良好。     

强化阿托伐他汀治疗对冠心病合并高尿酸血症患者PCI后Scr、hsCRP、NGAL的影响

目的：观察大剂量阿托伐他汀对冠心病合并高尿酸血症（HUA）患者经皮冠状动脉介入治疗（PCI）术后血清肌酐（Scr）、高敏C反应蛋白（hsCRP）及中性粒细胞明胶酶脂质相关运载蛋白（NGAL）的影响,探讨阿托伐他汀对肾脏的保护作用。方法：择期PCI的冠心病合并HuA患者60例,随机分为阿托伐他汀强化治疗组（31例,围手术期40mg／d）和常规治疗组（29例）。分别于术前,术后24h、72h测定血清Scr、hsCRP、NGAL水平。结果：两组Scr水平在术后24h升高,72h回落,无显著差异（P〉0．05）;hsCRP、NGAL术后24h升高,强化治疗组升高程度明显低于常规治疗组[hsCRP（6．8±2．1）mg／L比（8．4±3．8）mg／L,NGAL（57．1±12．7）ng／ml比（66．2±17．9）ng／ml],P均〈0．05;术后72h回落,与常规治疗组比较,强化治疗组hsCRP[（6．6±2．4）mg／L比（5．5±1．5）mg／L]、NGAL[（52．1±12．9）ng／ml比（45．6±9．7）ng／m1]水平均明显降低（P〈0．05）。结论：短期内大剂量应用阿托伐他汀可以降低冠心病合并高尿酸血症患者PCI术后血清高敏C反应蛋白和中性粒细胞明胶酶脂质相关运载蛋白升高的程度,从而达到保护肾脏的作用。     

阿托伐他汀对高脂血症患者血脂、血清一氧化氮和血浆内皮素的影响及停药后各项指标的变化

目的探讨阿托伐他汀对高脂血症患者血脂和血清一氧化氮(NO)、血浆内皮素(ET-1)的于影响及停药后各项指标的变化。方法 40例原发性高脂血症患者每日服阿托伐他汀10mg共用8周,第9周停药。分别于服药前、8周末及停药4周末取空腹静脉血,均行血三酰甘油(TG)、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)、NO、ET-1测定。另选本院同期健康体检者40例作为对照组,要求采血前两周未服用任何药物。结果高脂血症患者血NO水平显著低于对照组,ET-1水平明显高于对照组(均P<0.01)。治疗8周末两组血HDL-C、NO水平显著升高、TG、TC、LDL-C、ET-1水平明显降低(P<0.01)。停药4周末TG、TC、LDL-C、和ET-1均较治疗8周末明显升高,而HDL-C、NO明显下降,差异有统计意义(P<0.01)。结论阿托伐他汀钙能够改善高脂血症患者血脂及内皮功能,且需要长期坚持服用。     

Combined Hyperlipidemia In A Single Subject With Tetraplegia: Ineffective Risk Reduction After Atorvastatin Monotherapy

Abstract

Background/Objective: Effects of atorvastatin (Lipitor) drug monotherapy (1 0 mg daily) on fasting blood Iipid profiles and cardiovascular disease (CVD) risks were examined for a single subject with C5-C6 tetraplegia. Routine fasting Iipid profiles were analyzed by standard biochemistry techniques for total cholesterol (TC) , triglycerides (TG) , low-density lipoprotein-cholesterol (LDL-C) , and high-density lipoprotein-cholesterol (HDL-C). Lipid profiles were analyzed on 3 occasions before drug therapy was initiated and 3 months after therapy commenced. The TC:HDL and LDL:HDL ratios were computed for all sampling times and used to assess pretreatment and post-treatment CVD risk.

Results: Fasting TC, TG, and LDL-C were all significantly reduced by therapy. The pretreatment HDL-C of 3 5 mg/ dl was lowered to 21 mg/ dl. As a result, the TC:HDL risk ratiowas only marginally reduced from 6 .6 to 6.4, whereas the LDL:HDL risk ratio remained unchanged by treatment.

Conclusions: In this man with tetraplegia, atorvastatin drug monotherapy rapidly lowered TC, TG, LDL-C, and HDL-C. However, the TC: HDL ratio, considered the best predictor of CVD risk, was unchanged.     

Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in Alzheimer’s disease

Abstract

Objectives: To examine and compare the pleiotropic effects on oxidative stress and metabolic signaling pathways of atorvastatin and pitavastatin in mouse model of Alzheimer’s disease (AD).

Methods: We gave the transgenic (Tg) mice either atorvastatin or pitavastatin from 5–20 months (M) of age, and performed immunohistological analysis [4-hydroxy-2-nonenal (4-HNE)-positive, advanced glycation end products (AGEs), low-density lipoprotein receptor (LDL-R)-positive neurons, apolipoprotein E (ApoE)-positive senile plaque (SP), and insulin receptor (IR)-positive endothelium], and biochemistry analysis (adiponectin and leptin).

Results: The numbers of 4-HNE- and AGE-positive neurons and the sum of ApoE-positive SP size progressively increased with age in amyloid precursor protein (APP)-Tg mice, while the amount of IR-positive endothelium and the number of LDL-R-positive neurons decreased. Adiponectin and leptin serum levels were lower in APP-Tg mice than in non-Tg mice. Treatment with statins reduced the number of AGE-positive neurons from as early as 10 M, preserved the numbers of 4-HNE- and LDL-R-positive neurons and the amount of IR-positive endothelium at 15 M, and reduced the sum of ApoE-positive SP size and adiponectin serum level at 20 M.

Discussion: Atorvastatin and pitavastatin reduced the level of oxidative stress, as revealed by the presence of 4-HNE and AGE, in AD mouse brains, and that treatment with statins improves insulin signaling and LDL-R/ApoE systems. The beneficial effects of these statins may be associated with direct pleiotropic effects on AD mouse brains, indirect effects through improving the serum adiponectin/leptin balance, or both.