氟伐他汀、苯那普利对自发性高血压大鼠血管平滑肌细胞L型钙通道α1C表达的影响

背景在血管平滑肌细胞(VSMC)中,L 型钙通道是提高细胞内游离钙离子浓度的主要途径,L 型钙通道中的α1亚单位(LTCCα1C)是决定 L 型钙通道电压依赖性和药物敏感性的重要部位。目的通过比较LTCCα1C亚基在正常大鼠和自发性高血压大鼠(SHR)胸主动脉 VSMC 表达的差异,以及经苯那普利和氟伐他汀干预后的变化.来阐明氟伐他汀、苯那普利抗高血压血管重构的分子机制。方法 12周龄雄性 SHR 24只,随机分为空白对照组(SHRc 组,n=8)、氟伐他汀治疗组[SHRf 组:20 mg/(kg·d),n=8]、苯那普利组[SHRb 组:10 mg/(kg·d),n=8],年龄和体质量匹配的 Wistar-Kyoto(WKY)大鼠为正常对照组(n=8)。灌胃法给药18周后苏木精一伊红染色计算胸主动脉血管壁/腔面积,RT-PCR 法、免疫组织化学法、Western blotting 法比较各组大鼠胸主动脉 LTCCα1C 的表达。结果 SHRc 组的胸主动脉壁腔面积比(壁/腔)与 WKY 组比较显著增高(0.30±0.01比WKY:0.1 9±0.02,P<0.05)。氟伐他汀和苯那普利降低大鼠胸主动脉的壁/...     

Beneficial Effects of Fluvastatin on Liver Microcirculation and Regeneration After Massive Hepatectomy in Rats

Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (α-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells.     

氟伐他汀对正常血脂兔心肌缺血再灌注损伤的保护作用

目的　观察氟伐他汀对正常血脂兔的心肌缺血再灌注损伤有无保护作用及其可能原因。方法　将2 4只标准饲养的日本大耳白兔随机分为假手术组、缺血再灌注组和氟伐他汀组,氟伐他汀组在行缺血再灌注术前给予氟伐他汀10mg/ (kg·d)干预一周。建立心肌缺血再灌注模型,监测血流动力学变化;检测乳酸脱氢酶和肌酸激酶活性;以Evans蓝和TTC双重染色方法测量心肌梗死面积。取局部梗死区及对应部位心肌检测诱导型一氧化氮合酶活性的表达。结果　与缺血再灌注组比较,氟伐他汀组心肌梗死面积、乳酸脱氢酶1及肌酸激酶活性均显著减小(P <0 .0 5及P <0 .0 1) ;缺血即刻始氟伐他汀组各时间点较缺血再灌注组左心室舒张末压减小(P <0 .0 5 ) ,左心室内压变化最大速率(±dp/dtmax)增大(P <0 .0 5 ) ;缺血再灌注组及氟伐他汀组总一氧化氮合酶活性均显著高于假手术组(P <0 .0 5 ) ,缺血再灌注组诱导型一氧化氮合酶活性与总一氧化氮合酶活性比值显著大于假手术组和氟伐他汀组(P <0 .0 1)。结论　氟伐他汀可以保护正常血脂兔的心肌缺血再灌注损伤,其机制可能部分与调节一氧化氮合酶活性的表达有关。     

Effect and mechanism of fluvastatin on the expression of fibronectin in human peritoneal mesothelial cells induced by high?glucose peritoneal dialysate

Objective To explore the effect and mechanism of fluvastatin on the expression of fibronectin(FN) in human peritoneal mesothelial cells (HPMCs) induced by high?glucose peritoneal dialysate (HGPDS). Methods Cultured HPMCs were randomly divided into control, HGPDS, HGPDS plus GSK650394 10-5 mol/L (the competitive inhibitor of SGK1), different concentrations of fluvastatin, fluvastatin 10-6 mol/L and GSK650394 10-5 mol/L alone. The morphology change of HPMC was observed by light microscopy. The cellular viability was detected by MTT colorimetry. The mRNA and protein expressions of serum and glucocorticoid?inducible kinase 1 (SGK1) and FN were detected by RT?PCR, Western blotting or ELISA. Results After incubation with HGPDS, the cell morphology changed from typical cobblestone?like appearance to fibroblast?like appearance, and the cell viability was inhibited significantly (P<0.05). Fluvastatin 10?6mol/L and GSK650394 could improved the cell morphology and the cell viability injured by HGPDS (P<0.05). Compared with the normal control group, the mRNA and protein expressions of SGK1 and FN increased significantly in HPMC treated with HGPDS(P<0.05). GSK650394 significantly decreased the high expression of SGK1 and FN (P<0.05), also the fluvastatin had same effects as GSK650394 in dose?dependent manner (P<0.05). Conclusions High?glucose peritoneal dialysate can increase FN expression in human peritoneal mesothelial cells, which can be attenuated by fluvastatin. The protective role of fluvastatin in HPMC may be partially achieved through the signal pathway of SGK1.     

氯吡格雷联合氟伐他汀治疗脑梗死临床观察

目的探讨氯吡格雷联合氟伐他汀治疗脑梗死患者的临床效果。方法选取2013-01—2014-06我院神经内科收治的68例脑梗死患者,采用数字列表法将其随机分为常规组和联合组,常规组采用传统治疗方式,联合组采用氯吡格雷联合氟伐他汀治疗,对比2组患者的临床治疗效果,并评估2组患者的神经功能缺损情况。结果联合组总有效率94.10%,明显高于常规组,差异有统计学意义(P0.05)。治疗后,2组神经缺损功能评分和生活能力评分和治疗前比较,差异均有统计学意义(P0.05);联合组神经功能缺损评分明显低于常规组,生活能力评分明显高于常规组,差异均有统计学意义(P0.05)。结论氯吡格雷联合氟伐他汀治疗脑梗死效果显著,能够有效阻止病情恶化,改善患者的身体质量,提高其神经功能评分,值得临床推广使用。     

氟伐他汀联合氯吡格雷治疗脑梗死的疗效及对血浆内皮素与凝血系统的影响

目的探讨氟伐他汀联合氯吡格雷治疗脑梗死的疗效及对血浆内皮素与凝血系统的影响。方法选取我院2013-05—2015-05收治的120例脑梗死患者,采取随机数字表法分为基础组与联合组各60例,基础组仅给予抗血小板、降血压等常规治疗,联合组在其基础上加用氟伐他汀联合氯吡格雷治疗,比较2组临床疗效、血脂变化情况、血浆内皮素、凝血系统变化及神经功能缺损评分(NHISS)。结果基础组总有效率71.67%,联合组为91.67%,联合组显著高于基础组,差异有统计学意义(χ~2=5.42,P0.05)。2组治疗前后TC、TG、LDL-C、HDL-C、ET水平相比均具有显著差异(t=2.89,P0.05;t=3.55,P0.05;t=3.71,P0.05;t=3.34,P0.05;t=3.56,P0.05)。基础组治疗后与联合组治疗后TT、PT、FIB水平相比均具有显著差异(t=2.59,P0.05;t=3.91,P0.05;t=3.28,P0.05)。2组治疗后NIHSS评分相比有显著性差异(t=2.67,P0.05)。结论氟伐他汀联合氯吡格雷治疗脑梗死临床疗效显著,可有效改善异常指标水平,值得推广与应用。     

氟伐他汀对心肌梗死大鼠左室重塑和功能的影响

目的探讨羟甲基戊二酰辅酶A(HMGCoA)还原酶抑制剂氟伐他汀对急性心肌梗死(AMI)大鼠左室结构和功能的影响。方法雌性SD大鼠AMI后6h随机分为AMI组和氟伐他汀组;另设假手术组。三组大鼠直接灌胃给药或自来水8周后行高频多普勒超声、血流动力学、心脏重塑指标及左心室心肌α、β肌球蛋白重链(α、βMHC)mRNA表达的测定。结果与假手术组相比,AMI组左室舒张末期内径(LVEDD)、左室舒张末期容积(LVEDV)、E峰、E峰减速度、E/A、左室舒张末压(LVEDP)、左、右心室心肌肥厚指数、非梗死区胶原容积分数(CVF)和βMHCmRNA均明显增加(P<0.01),左室短轴缩短率(FS)、射血分数(EF)和αMHCmRNA显著降低(P<0.01)。与AMI组相比,氟伐他汀组的LVEDD、LVEDV、E峰、E峰减速度、E/A、LVEDP、左、右心室心肌肥厚指数、CVF和βMHCmRNA均显著降低或减少(P<0.01),FS、EF和αMHCmRNA显著升高(P<0.01)。结论氟伐他汀能抑制大鼠AMI后左室重塑,改善血流动力学异常和左室功能。     

氟伐他汀对缺血再灌注高脂血症兔心肌一氧化氮合酶活力的影响

目的:探讨氟伐他汀对高脂血症兔心肌缺血再灌注损伤的保护作用及机制。方法:自制脂肪乳剂灌胃建立兔高脂血症模型。将40只高脂血症日本大耳白兔随机分为4组(每组10只):单纯缺血再灌注组(IR 组)、假手术组(S组)、氟伐他汀10 mg/kg剂量组(F10组)和75 mg/kg剂量组(F75组),实验中监测各组大兔心电图及心功能,实验毕取心肌组织,Evans蓝及氯化三苯基四氮唑(TTC)双重染色测心肌梗死程度,比色法测心肌一氧化氮合酶(NOS)同工酶活力。结果:缺血再灌注后,与IR组相比,F10组和F75组诱导型NOS(iNOS)活力显著降低(均P<0.01),心肌梗死程度显著降低(P<0.01),心功能显著改善。F75组与F10组相比,iNOS活力显著降低(P<0.05),心肌梗死程度显著降低(P<0.05),各心功能参数有改善趋势,但差异无统计学意义。结论: iNOS活力增高是心肌缺血再灌注损伤的重要因素,氟伐他汀可降低iNOS活力,降低心肌梗死程度,改善心功能,氟伐他汀75 mg/kg优于10 mg/kg。     

氟伐他汀对兔动脉粥样硬化血管壁NF-κB及ICAM-1表达的影响

目的:观察氟伐他汀对动脉粥样硬化(As)家兔模型血管壁核因子-kappaB(NF-κB)活性及mRNA、细胞间粘附分子-1(ICAM-1)表达的影响,以探讨氟伐他汀抗As的作用机制。方法:雄性新西兰家兔32只,随机分为对照组、高脂饮食组、氟伐他汀组。喂养12周后处死动物并留取主动脉标本,观察组织形态学变化,用免疫组化法观察NF-κB活性、ICAM-1表达,用原位杂交法观察NF-κBmRNA表达。结果:氟伐他汀组与高脂饮食组相比,As病变明显减轻(P<0.01);NF-κB活性由(40.3±5.9)%减弱为(17.3±2.4)%(P<0.01);NF-κBmRNA表达由(41.7±5.5)%减弱为(19.6±1.7)%(P<0.01);ICAM-1表达由(31.6±2.7)%减弱为(16.5±2.1)%(P<0.01)。结论:氟伐他汀抗As作用与抑制NF-κB活性,下调ICAM-1表达有关。     

一项多中心、前瞻性、观察性研究评价氟伐他汀钠胶囊每日80 mg治疗的有效性及安全性

目的观察对于氟伐他汀钠胶囊40 mg日一次使用不能达标的稳定型心绞痛或2型糖尿病患者,剂量增加为40 mg每日两次的有效性和安全性。方法多中心、前瞻性、观察性上市后临床监测研究。该研究共纳入251例高脂血症合并稳定型心绞痛或2型糖尿病患者,这些患者经氟伐他汀钠胶囊40 mg睡前一次口服治疗至少4周后,低密度脂蛋白胆固醇(LDLC)未达标(>100 mg/dL)。经医生判断后根据临床需要将剂量增加至40 mg每日两次,共观察8周。主要疗效指标为治疗8周时LDLC水平与患者入组时即药物剂量增加前(基线)相比的变化;次要指标为第8周时LDLC的达标率、空腹甘油三酯(TG)、总胆固醇(TC)及高密度脂蛋白胆固醇(HDLC)水平与基线相比的变化以及安全性和耐受性。结果意向治疗人群(ITT)251例。氟伐他汀钠胶囊40 mg每日两次治疗终点时(第8周)ITT人群的LDLC较基线显著降低,总ITT人群、稳定型心绞痛和2型糖尿病患者LDLC较基线的降幅分别为27.3%、25.3%和28.9%(P均<0.001)。研究结束时59.4%的患者LDLC达标(<100 mg/dL),稳定型心绞痛和2型糖尿病患者的达标率分别为52.9%和67.2%。TG水平较基线显著下降,总人群、稳定型心绞痛和2型糖尿病患者分别下降17.02%、16.50%和17.78%(P均<0.001)。4例患者(1.6%)转氨酶(ALT/AST)升高>3倍正常值上限(ULN),其中3例氟伐他汀减量至40 mg每日一次后继续使用,没有患者出现肝脏症状或胆红素异常。研究过程中没有患者报告肌肉症状和/或肌酸激酶(CK)升高>5×ULN。结论对于应用氟伐他汀钠胶囊40 mg每日不达标的稳定型心绞痛或2型糖尿病患者,剂量增加至80 mg每日可以明显改善达标率,并且具有良好的安全性和耐受性。