Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

辛伐他汀5mg与普伐他汀10mg治疗高胆固醇血症的比较

目的：探讨低剂量辛伐他汀治疗高胆固醇血症的临床疗效及耐受性。方法：低、中度原发性高胆固醇血症病人６２例，随机分为２组，Ａ组３１例（男性２６例，女性５例；年龄６４±ｓ１４ａ）采用辛伐他汀５ｍｇ，ｐｏ，ｑｄ。Ｂ组３１例（男性２５例，女性６例；年龄６１±１３ａ）采用普伐他汀１０ｍｇ，ｐｏ，ｑｄ。疗程均为４ｗｋ。结果：辛伐他汀组在降低ＴＣ，ＬＤＬ＿ｃｈ及提高ＨＤＬ＿ｃｈ的平均变化率上分别为１７％±９％，２５％±１２％（Ｐ＜０．０１）和１１％±１１％（Ｐ＞０．０５），与普伐他汀组疗效相当，组间比较，Ｐ值＞０．０５。２种药物治疗期间病人均无显著不良反应。结论：小剂量辛伐他汀疗效可与普伐他汀媲美，５ｍｇ／ｄ可作为治疗高胆固醇血症的起始剂量     

辛伐他汀对人低密度脂蛋白氧化修饰影响的实验研究

目的研究辛伐他汀在体外对低密度脂蛋白氧化修饰的影响.方法以低密度脂蛋白氧化修饰为模型,以硫代巴比妥酸反应物质(TBARS)生成量及相对电泳迁移率(REM)为指标,研究了辛伐他汀对铜离子(Cu2 )诱导低密度脂蛋白氧化修饰的抑制作用.结果随辛伐他汀浓度从1～10μmol/L的增加,TBARS值分别减少67.3%,73.9%,81.9%,REM值减少48.3%,55.2%,58.6%,呈浓度及时间依赖关系.其中10μmol/L辛伐他汀可几乎完全抑制低密度脂蛋白氧化.结论辛伐他汀在体外能明显抑制Cu2 诱导的低密度脂蛋白氧化修饰.     

辛伐他汀对早期糖尿病大鼠视网膜白细胞黏附的影响

目的 观察辛伐他汀（Sim）对白细胞在早期糖尿病大鼠视网膜毛细血管中黏附、堆积的影响,探索他汀类药物可能的非调脂性治疗作用.方法 Wistar大鼠40只,随机分为正常对照组、糖尿病组（DM）、糖尿病Sim组（DMsim）和糖尿病生理盐水组（DM saline）.腹腔注射链脲佐菌素（STZ）建立糖尿病模型,成模后Sim组予以Sim15 mg/（kg·d）;DMsim组等量灌胃,2周后处死动物,取右眼制备视网膜石蜡切片,行形态学观察及CD45-MAb免疫组织化学研究.结果 CD45在正常大鼠视网膜血管内皮细胞胞膜中有表达,DM组CD45的表达明显增加,与正常对照组、DMsim组比较差异有统计学意义（P＜O.05）.结论 早期糖尿病大鼠视网膜白细胞黏附性增加,Sim可显著地抑制白细胞在视网膜中的黏附和堆积,改善糖尿病大鼠视网膜微循环.     

辛伐他汀对CD40L介导的ECV-304细胞E选择素表达及粘附功能的影响

目的研究在人脐静脉内皮细胞中3-羟-3-甲基戊二酰辅酶A(HMG-CoA)还原酶对CD40/CD40L系统介导的粘附分子表达的影响,及对淋巴细胞与内皮细胞的粘附功能的影响。方法采用人脐静脉内皮细胞株ECV-304,CD40L干预,使之与其表面的CD40作用,用不同浓度辛伐他汀或辛伐他汀(5μmol.L-1)+甲羟戊酸干预,流式细胞术和RT-PCR检测干预前后E选择素(E-Selectin)的表达,流式细胞术检测CD40L介导的淋巴细胞与内皮细胞的粘附功能。结果不同浓度辛伐他汀可下调CD40L介导的E-Selectin的表达,并呈一定的剂量依赖性。甲羟戊酸(400μmol.L-1)抑制了辛伐他汀(5μmol.L-1)对E-Selectin表达的下调作用。辛伐他汀可降低CD40L介导的淋巴细胞与内皮细胞的粘附功能。结论他汀类药物的抗炎作用与抑制CD40-CD40L系统有关,其机制是通过抑制HMG-CoA还原酶而发挥作用的。     

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study

1It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44–129 weeks) after randomization. 3The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.     

阿托伐他汀与辛伐他汀治疗高脂血症的效果

目的分析在高脂血症患者治疗中应用阿托伐他汀和辛伐他汀的降脂效果。方法将2017年1月—2020年1月在我院医治的90例高脂血症患者随机设为两个组别,给予对照组(45例)辛伐他汀治疗,给予试验组(45例)阿托伐他汀治疗。观察两组患者治疗前后血脂水平和生化指标变化情况。结果试验组治疗后总胆固醇、三酰甘油、低密度脂蛋白胆固醇低于对照组,高密度脂蛋白胆固醇高于对照组,两组对比差异具有统计学意义(P<0.05)。两组患者治疗后肌酐、尿素氮指标差异无统计学意义(P>0.05)。结论阿托伐他汀和辛伐他汀应用于高脂血症患者治疗中均能起到不同程度的降脂效果,但阿托伐他汀的效果更好,安全可靠。     

辛伐他汀联合雷奈酸锶对成骨细胞及破骨细胞生物学特性的影响

目的探讨辛伐他汀(simvastatin,SIM)联合雷奈酸锶(strontium ranelate,SR)治疗对大鼠成骨细胞及破骨细胞生物学特性的影响。方法分离和培养大鼠成骨细胞和破骨细胞;使用SIM或SR和较低剂量SIM联合较低剂量SR处理大鼠成骨细胞和破骨细胞;用Western blot方法检测成骨细胞和破骨细胞中p-akt、p-gsk3β、β-catenin、p-β-catenin和NFATC1的蛋白水平。用相应的试剂盒测定ALP活性和TRACP活性。结果与单独使用SIM或SR相比,SIM+SR联合处理使成骨细胞活性明显增加,而破骨细胞分化和骨吸收能力明显降低(P<0.05)。进一步研究发现与单独使用SIM或SR相比,SIM+SR处理使成骨细胞中p-akt、p-gsk3β、β-catenin、p-β-catenin和NFATC1的蛋白水平显著增加(P<0.05);而破骨细胞中p-akt、p-gsk3β、β-catenin、p-β-catenin和NFATC1的蛋白水平显著降低(P<0.05)。结论较低剂量的SIM+SR比单独使用较高剂量的SIM或SR,更能显著通过AKT/GSK3β/β-catenin/NFATC1信号通路介导成骨细胞和破骨细胞功能。     

辛伐他汀对血管升压素诱导大鼠心脏成纤维细胞增殖的影响

目的　探讨辛伐他汀 (Simvastatin ,Sim)对血管升压素 (AVP)诱导的新生SD大鼠心脏成纤维细胞 (CFs)增殖的影响 ,为防治高血压心肌纤维化提供理论依据。方法　采用胰酶消化、差速贴壁法培养新生SD大鼠CFs,以3H 胸腺嘧啶核苷 (3H TdR)掺入法测定DNA合成、四氮唑盐 (MTT)比色法测定细胞数目 ,分别观察不同浓度Sim对AVP诱导CFs增殖的作用及甲羟戊酸 (Meval onate,MVA)干预的影响。结果　①CFs(2 0 0个细胞 )的3H TdR掺入率随着Sim干预浓度的增加而降低 ,其中 1 0 - 6mol/LSim和 1 0 - 5mol/LSim组的3H TdR掺入率分别为 (1 1 75± 2 0 2 6 6 )、(771± 1 6 4 86 )cpm ,明显低于对照组 (1 95 5± 3 72 45 )cpm(P <0 0 1 ) ;②MTT比色法A490 值随Sim浓度的增加而降低 ,其中 1 0 - 6、1 0 - 5mol/LSim组的A490 值分别为 0 2 1 5± 0 0 4 1和 0 1 6 3± 0 0 1 8,均较对照组A490值 0 3 93± 0 0 4 8显著降低 (P <0 0 1 ) ;③ 1 0 - 5mol/LSim +1 0 - 3mol/LMVA组的3H TdR掺入率、MTT比色法A490 值分别为 (1 995±3 5 3 83 )cpm和 0 41 8± 0 0 4 5 ,均显著高于 1 0 - 5mol/LSim组 (P <0 0 1 )。结论　辛伐他汀可抑制AVP诱导的CFsDNA的合成和细胞数目增加 ,提示Sim可抑制CFs增殖 ,其机制可能通过甲     

泽之浩治疗高脂血症临床疗效和安全性的研究

目的：评价泽之浩（国产辛伐他汀）治疗高脂血症,尤其是高胆固醇血症和混合型高脂血症的临床疗效及安全性。方法：选择高脂血症患者,有冠心病或冠心病危险因素的高脂蛋白血症患者54例,给予泽之浩10mg/d;4周后如未达有效标准,均可加量至20mg/d,治疗8周,观察降脂疗效和不良反应。结果：（1）泽之浩治疗后,1例患者因血清谷丙转氨酶升高而中途退出研究,其余患者(n=53)的总胆固醇（TC）,甘油三酯（TG）,低密度脂蛋白胆固醇（LDL－C）均明显降低,高密度脂蛋白胆固醇（HDL－C）明显升高（P均＜0．05）,（2）高胆固醇血症（n=20)用泽之浩治疗,TC,LDL－C,（TC－HDL－C）／HDL－C显著下降（P均＜0．01）,（3）对于混合高脂血症患者（n=14),泽之浩可使TC,LDL－C和TG显著下降（P＜0．01,P＜0．05）。（4）泽之浩调脂幅度与治疗前的TC和TG水平相关。（5）泽之浩调脂的总有效率为88．7％,总显效率为83．0％,结论：泽之浩有明显的降低TC,LDL－C,TG和（TC－HDL－C）／HDL－C和升高HDL－C的作用,其不良反应较轻微,常用剂量10mg/d,少数TC,LDL－C较高者可用20mg/d。