Simvastatin suppresses LPS-induced Akt phosphorylation in the human monocyte cell line THP-1

BACKGROUND: Activation of the small GTPase, Rac, requires post-translational modification by isoprenylation. Statins interfere with this process by blocking the synthesis of isoprenoid intermediates. The protein kinase Akt is a multifunctional regulator of cell behavior that has been linked to Rac activation. We have shown that lipopolysaccharide (LPS) stimulation leads to Rac activation in THP-1 cells. Therefore, we hypothesized that LPS stimulation would also activate Akt, a downstream effector of Rac, and that this may be blocked by statin pretreatment. MATERIALS AND METHODS: THP-1 cells were maintained in 1% fetal calf serum with or without 20 microM simvastatin for 24 h, followed by LPS stimulation for increasing time. Cytoskeletal changes were observed using Alexa-Phalloidin. Akt was immunoprecipitated from total cell lysate. Activated Akt was detected by immunoblotting with a phospho-Akt antibody and was quantified by image densitometry. RESULTS: LPS stimulation of THP-1 cells results in membrane ruffling and cell polarization. Furthermore, LPS increased Akt activation in THP-1 cells when compared with the nonstimulated controls. Akt phosphorylation peaked after 15 min of LPS stimulation and was suppressed by pretreatment with simvastatin. CONCLUSIONS: These data demonstrate that LPS stimulation leads to increased Akt phosphorylation, which can be suppressed with simvastatin pretreatment. This suggests one possible mechanism through which simvastatin could modulate LPS-induced signaling events in monocytes to improve the host response to Gram-negative infections.     

高压培养对血管内皮细胞t-PA和PAI-1的影响及卡托普利干预的效果

目的：高血压常伴有纤溶功能的异常,但其机制尚不清楚。本研究拟观察高静水压培养对人脐静脉内皮细胞（HUVECs）t-PA和PAI-1的影响以及卡托普利的干预效果,并探讨其可能的作用机制。方法：选用第4～6代HU-VECs,接种于24孔培养板中。依培养压力分为3组：大气压组（0mmHg）,中压组（90mmHg）,高压组（180mmHg）。在同一压力组,根据不同药物干预又分为两个亚组。即对照组（Ctrl）和卡托普利组（Cap,10^-5mol/L）。每组6份标本。采用ELISA法测定上清液t-PA和PAI-1的抗原浓度,并用细胞内总蛋白进行标化（单位：ng/μg proteins）。同时测定细胞内Ca^2＋浓度（nmol/L）。结果：与大气压组相比,中压和高压组t-PA浓度均显著降低,PAI-1浓度显著增高,t-PA/PAI-1比值显著降低,[Ca^2＋]i也显著增高。卡托普利对大气压组的t-PA、PAI-1和[Ca^2＋]i无显著影响,但在两个高压组,卡托普利显著升高t-PA浓度,显著降低PAI-1浓度,t-PA/PAI-1比值显著升高,[Ca^2＋]i显著地降低。结论：高静水压可损害内皮细胞的纤溶功能,而卡托普利的干预可降低高压所升高的[Ca^2＋]i,并改善高静水压对内皮细胞纤溶功能的影响。     

辛伐他汀治疗冠心病心绞痛急性发作期效果研究

目的探讨对冠心病心绞痛急性发作期患者开展辛伐他汀治疗的临床效果以及对TC、TG的影响。方法选取2013年2月—2014年2月收治的冠心病心绞痛急性发作期患者98例,随机分为对照组与观察组各49例,两组患者均开展临床常规治疗,观察组患者增加辛伐他汀药物。观察两组患者治疗前后的心绞痛持续时间与发作次数,并通过全自动分析仪检测TC、TG、HDL-C、LDL-C。计量资料采用t检验,计数资料采用χ2检验,P0.05为差异有统计学意义。结果治疗后观察组发作情况好于对照组,差异均有统计学意义(均P0.05)。治疗后观察组患者的TC、TG、HDL-C、LDL-C均显著好于对照组,差异均有统计学意义(均P0.05)。对照组总有效率为79.6%,观察组为93.9%,观察组显著好于对照组,差异有统计学意义(P0.05)。结论对冠心病心绞痛急性发作期患者应用辛伐他汀,可显著缓解心绞痛的发作情况,并且对TC、TG有显著的改善效果,值得进一步推广应用。     

Determination of simvastatin-induced changes in bone composition and structure by Fourier transform infrared spectroscopy in rat animal model

Simvastatin is a hypolipidemic drug which is used to control hypercholesterolemia and to prevent cardiovascular disease. In the current study, the effects of high and low doses of simvastatin treatment on tibia of healthy rats were investigated. Wistar rats were used for the control, 20 mg and 50 mg simvastatin-treated groups. Molecular investigations were performed using Fourier transform infrared spectroscopy. In the bones of the two groups of simvastatin-treated rats, the relative mineral/matrix ratio (p < 0.001), relative carbonate content (p < 0.001), carbonate/amide I ratio (p < 0.001) and crystallinity (p < 0.001) decreased significantly compared to the control group. Low dose of simvastatin treatment is more effective in reducing the relative carbonate content indicating the amount of carbonate substitution for phosphate in the mineral crystal. The olefinic band almost disappeared in the high dose of simvastatin-treated group which implies a decrease in unsaturation and an increase in lipid peroxidation. The higher frequency value and the bandwidth of CH₂ asymmetric stretching band for the 50 mg treated group imply more disordered (p < 0.001) and fluid (p < 0.001) membrane structure. Low dose of simvastatin is more effective in strengthening the bone than high dose simvastatin treatment. High dose simvastatin treatment induces lipid peroxidation and changes the lipid composition and concentration, which are known to affect membrane physical properties.     

血脂康和辛伐他汀治疗高脂血症的疗效比较

目的：比较血脂康与辛伐他汀对高脂血症的疗效。方法：60例高脂血症患者随机分为两组，血脂康组30例，口服血脂康0.6g，早晚各1次。辛伐他汀组30例，服辛伐他汀20mg，晚餐后顿服，疗程均为4周。结果：两组患者治疗后TC、TG、LDL－C下降，HDL－C升高；组间无差别（P＞0.05)；两组均无明显不良反应。结论：血脂康与辛伐他汀疗效相似，均为安全、有效的降脂药物，但血脂康比辛伐他汀价廉。     

普罗布考和辛伐他汀联合治疗脑动脉狭窄的疗效观察

目的探讨脑动脉狭窄药物治疗的疗效。方法回顾性分析2007至2010年经颅多普勒检查诊断的脑动脉狭窄患者240例。将240例大脑中脑动脉狭窄患者随机分成4组,A组联合应用普罗布考与辛伐他汀进行治疗。B组应用辛伐他汀进行治疗。C组应用普罗布考治疗。D组应用阿司匹林作为对照组。分别于用药前、用药后3~24个月随访,记录不良反应事件发生情况,复查TCD检查结果将血管转归分为好转组、稳定组、进展组,评价其预后并就药物疗效进行分析。结果 A组总有效率25%,B组有效率18.3%,C组20%,D组13.3%。结论联合用药效果好于单一用药及不用药物,有统计学意义,P<0.01。普罗布考及辛伐他汀比较无统计学差异。应用药物效果好于不用药物。有统计学意义,P<0.01。对于脑动脉狭窄的患者,如未行手术治疗,可应用药物治疗。     

辛伐他汀减轻载脂蛋白E~(-/-)小鼠氧化应激及小窝蛋白1的表达

背景氧化应激损伤内皮是动脉粥样硬化的始动因素,他汀对于动脉粥样硬化的干预主要集中在粥样硬化斑块形成之后,而对于粥样硬化斑块形成之前的研究较少。目的观察辛伐他汀对载脂蛋白(apo)E~(-/-)小鼠氧化应激及主动脉内皮小窝蛋白l的影响,探讨辛伐他汀在动脉粥样硬化一级预防中保护内皮功能的机制。方法24只6周龄雄性 apoE~(-/-)小鼠,随机等分为两组:对照组、辛伐他汀[5 mg/(kg·d)]治疗组,4周后处死动物。常规生物化学法测定血总胆固醇(TC)、超氧化物歧化酶活性(SOD)、丙二醛(MDA)和血清一氧化氮(N0)含量。采用苏木素伊红(HE)染色法观察小鼠主动脉内皮组织,免疫组织化学法分析小鼠主动脉内皮的小窝蛋白1的表达。结果两组间血脂水平无显著性差异。辛伐他汀治疗组主动脉内皮组织的损伤减轻(损伤阳性率33.3%比对照组:75%,P<0.05)。治疗4周后,辛伐他汀治疗组 SOD[(135.3±5.5)U/L 比对照组:(97.2±7.6)U/L,P<0.01)和 NO[(28.4±4.1)μmol/L 比对照组:(12.3±2.1)μmol/L,P<0.01]均明显升高,MDA 显著减低[(10.5±...     

辛伐他汀和阿司匹林对大剂量VitD3致大鼠血管钙化的预防

目的研究辛伐他汀和阿司匹林对大鼠血管钙化的治疗作用。方法用大剂量维生素D3造成大鼠血管钙化模型,同时分别用辛伐他汀和辛伐他汀加阿司匹林进行治疗,比较模型组和治疗组大鼠主动脉主动脉血管钙化程度及其血脂水平。结果模型组和治疗组大鼠主动脉均出现钙化,辛伐他汀组大鼠血管钙含量、钙化面积百分比及血清总胆固醇含量较模型组均有不同程度的下降,辛伐他汀加阿司匹林组较模型组无明显改善。结论辛伐他汀对维生素D3造成的大鼠血管钙化有治疗作用。     

声学密度定量技术评价舒降之对动脉粥样硬化的消退作用

目的　用声学密度定量技术评价舒降之治疗前后动脉粥样硬化的消退作用。方法　分别测定舒降之组及其它 2个对照组治疗前后颈动脉正常内膜厚度、声学密度值及各型斑块的声学密度值。结果　舒降之组内膜 -中层厚度 (IMT)呈下降趋势 ,脂质斑块数目减少 ,脂质斑块及复合斑块的标化 IBS值与治疗前比较有统计学差异 ,标化 IBS值变化率与对照组有显著性差异 (P均 <0 .0 5 )。结论　舒降之能逆转早期动脉粥样硬化斑块 ,且能增大斑块密度 ,起到稳定斑块的作用 ,声学密度定量技术对于观察动脉粥样硬化病变的进展和评价降脂治疗结果具有实用价值。     

辛伐他汀联合阿司匹林对糖尿病肾微血管病变患者炎症因子的影响

目的 探讨糖尿病肾微血管病变患者血清P-选择素、肿瘤坏死因子-α(TNF-α)、高敏C-反应蛋白(hs-CRP)、白介素-1β(IL-1β)、细胞间粘附分子(ICAM)的临床意义及辛伐他汀联合阿司匹林治疗糖尿病肾微血管病变的机制.方法 用ELISA法测定各组以及糖尿病肾微血管病变组患者用辛伐他汀联合阿司匹林治疗后上述血清因子的变化水平.结果 ①糖尿病各组血清P-选择素、TNF-α、hs-CRP、IL-1β、ICAM均高于正常对照组(均P<0.01).②P-选择素、TNF-α、hs-CRP、IL-1β、ICAM在治疗8周时与治疗前比较均有明显下降(均P<0.05),治疗16周时进一步下降(P<0.01),以后保持稳定至21周.结论 ①P-选择素、TNF-α、hs-CRP、IL-1β、ICAM参与糖尿病肾微血管病变的发生发展,是糖尿病肾微血管病变的早期预测因子;②辛伐他汀联合阿司匹林治疗糖尿病肾微血管病变的机制可能是通过抑制炎症因子的表达,直接或间接影响系膜细胞增殖和系膜基质增生.