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.     

阿托伐他汀对进展性脑卒中治疗作用的探讨

目的探讨他汀类药物对进展性脑卒中的治疗作用。方法对发病在48 h内的105例进展性脑卒中患者临床资料进行研究。入选病例分为他汀治疗组及对照组:对照组47例采用常规治疗,未予阿托伐他汀治疗;他汀治疗组58例,在常规治疗基础上,每晚睡前口服阿托伐他汀钙20 mg·d-1。两组患者治疗前和治疗后14d采用NIHSS评分评价神经功能缺损情况。结果他汀治疗组NIHSS评分改善显著优于对照组(P<0.0 5)。结论他汀类药物可提高进展性脑卒中患者的疗效。     

舒血宁注射液联合阿托伐他汀治疗老年慢性硬膜下血肿的临床研究

目的探讨舒血宁注射液联合阿托伐他汀治疗慢性硬膜下血肿的临床疗效。方法选取2016年1月—2017年1月在天津医科大学总医院滨海医院治疗的慢性硬膜下血肿患者76例,依据治疗方案的差别分为对照组(38例)和治疗组(38例)。对照组口服阿托伐他汀钙片,20 mg/次,1次/d。治疗组在对照组的基础上静脉滴注舒血宁注射液,20 mL加入5%葡萄糖溶液250 mL,1次/d。两组患者均治疗30 d。评价两组患者临床疗效,同时比较治疗前后两组患者CSS和ADL评分以及血肿量和血清学指标。结果治疗后,对照组和治疗组的总有效率分别为81.58%、97.37%,两组比较差异具有统计学意义(P0.05)。治疗后,两组CSS评分与血肿量均显著降低,ADL评分升高,同组比较差异具有统计学意义(P0.05);且治疗组CSS和ADL评分及血肿量均显著优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清神经元特异性烯醇化酶(NSE)、基质金属蛋白酶-9(MMP-9)、脑源性神经营养因子(BDNF)水平显著降低,同组比较差异具有统计学意义(P0.05);且治疗组上述血清学指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论舒血宁注射液联合阿托伐他汀治疗慢性硬膜下血肿临床疗效显著,可有效改善神经功能和促进血肿吸收,具有一定的临床推广应用价值。