Effects of rosuvastatin on endothelial function in patients with familial combined hyperlipidaemia (FCH)

ABSTRACT

Objective: Although several studies have reported a positive effect of statins on endothelial vasoreactivity, most studies performed in subjects with type 2 diabetes mellitus report no effect at all. This lack of effect may be related to the existence of insulin resistance, or to insufficient lowering of atherogenic (apo)lipoproteins. Therefore, we tested in this study whether treatment of insulin resistant familial combined hyperlipidaemia (FCH) patients with a high dose (40?mg/day) of the potent rosuvastatin was able to improve endothelial function, without necessarily improving insulin sensitivity.

Research design and methods: In a double-blind randomised crossover study, 18 subjects with FCH (without evident cardiovascular disease, mean [standard deviation] age 54 [7] years) underwent a 4‐week run-in period after which they were randomised to treatment with placebo once daily for 12 weeks, followed by rosuvastatin 40?mg/day for 12 weeks or vice versa. Endothelial function was determined after 8 and 12 weeks of both treatment periods, respectively, by measurement of flow-mediated vasodilation (FMD) using high-resolution ultrasound and by measurement of vasodilator response to intrabrachial acetylcholine (Ach) by venous occlusion plethysmography (forearm blood flow [FBF]).

Results: Plasma levels of lipids, (apo)lipoproteins and high-sensitivity C‐reactive protein (hsCRP) improved significantly after rosuvastatin therapy compared to placebo. However, rosuvastatin had no effect on homeostasis model assessment (HOMA)-indices or on vasodilator responses to intra-brachial acetylcholine-infusion (FBF-ratio increased from a mean of 1.28 [SD: 0.46] to 5.82 [3.44] after rosuvastatin and from 1.33 [0.67] to 5.99 [3.89] after placebo, p = 0.35). Endothelium-dependent FMD was also unchanged (1.6% [3.1%] vs. 3.2% [3.5]%, p = 0.56 rosuvastatin vs. placebo, respectively).

Conclusion: In patients with FCH, a 12‐week treatment of rosuvastatin 40?mg/day did not improve endothelial function (either in large conduit vessels or in resistance vessels), despite significant improvements in plasma lipids, (apo)lipoproteins. and low-grade inflammation.     

瑞舒伐他汀联合前列地尔治疗短暂性脑缺血发作临床观察

目的观察瑞舒伐他汀及前列地尔治疗短暂性脑缺血发作(TIA)的临床效果。方法随机将符合诊断标准的TIA患者100例分为观察组和对照组各50例,观察组在对照组常规治疗基础上联合应用瑞舒伐他汀及前列地尔,观察2组治疗后的临床效果及治疗前后低密度脂蛋白、高密度脂蛋白、甘油三酯、胆固醇变化。结果观察组总有效率92%,对照组80%,两者相比差异有统计学意义(P<0.05),2组低密度脂蛋白、高密度脂蛋白、甘油三酯、胆固醇治疗前后比较差异有统计学意义(P<0.05)。结论应用瑞舒伐他汀联合前列地尔治疗TIA疗效显著,值得临床推广应用。     

Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats

The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5 mg/kg) alone or in combination with rosuvastatin (RSU) (10 mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats.     

Study on the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats

In the present study,we aimed to investigate the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats.Coadministration of repaglinide (0.5 mg/kg, 1 mg/kg and 2 mg/kg) for 7 d significantly increased the AUC_0–24 and C_max of rosuvastatin (P<0.01), but dramatically decreased the CL/F of rosuvastatin (P<0.01) after a single dose of rosuvastatin (10 mg/kg). There were no obviously changes in the parameters of T_max and t_1/2. Coadministration of repaglinide also decreased the liver distribution of rosuvastatin (P<0.01). Coadministration of rosuvastatin (20 mg/kg) for 7 days significantly increased the AUC_0–12 and C_max of repaglinide (P<0.05), and decreased the CL/F of repaglinide (P<0.01) after a single dose of repaglinide (1 mg/kg). The liver distribution of repaglinide was also decreased (P<0.01). Our animal study indicated that repaglinide could significantly affect the pharmacokinetics and liver distribution of rosuvastatin in rats and vice versa.     

瑞舒伐他汀对脑梗死患者脑血流动力学的影响研究

目的：研究瑞舒伐他汀对脑梗死患者血流动力学的影响。方法选取2011年2月—2014年2月我院神经内科收治的脑梗死患者60例，按照随机数字表法分为治疗组和对照组，每组30例。两组患者均采用神经内科常规治疗，治疗组加用瑞舒伐他汀，治疗3个月后，观察两组患者脑血流动力学改变情况。结果治疗前，两组患者血流动力学指标比较，差异无统计学意义（P 〉0.05）；治疗组患者治疗后双侧大脑动脉平均血流速度以及搏动指数较治疗前改善，差异有统计学意义（P 〈0.05）；对照组患者治疗后血流动力学指标与治疗前比较，差异无统计学意义（P 〉0.05）；治疗组患者治疗后双侧大脑搏动指数较对照组低，差异有统计学意义（P 〈0.05）。结论瑞舒伐他汀可有效改善脑梗死患者血流动力学指标，有助于患者恢复健康。     

瑞舒伐他汀隔日与每日治疗对血脂异常患者血脂及炎症标志物的影响

目的研究瑞舒伐他汀隔日给药10mg与每日给药10mg对血脂异常患者的血脂和炎症标志物的治疗差异。方法将37例患者随机分为2组,分别接受瑞舒伐他汀隔日给药10mg(N=19)和每日给药10mg(N=18)治疗6周后,比较用药前后血清中的低密度脂蛋白胆固醇(LDL-C),和血浆中C-反应蛋白(CRP)、白细胞介素-6(IL-6)的浓度变化。结果服药6周后,隔日治疗组和每日治疗组患者血清LDL-C、CRP、IL-6浓度与治疗前相比均有明显下降,高密度脂蛋白胆固醇和甘油三酯均有明显改善,但治疗效果两组间相比无统计学差异(P>0.05)。结论 10mg瑞舒伐他汀隔日治疗和每日治疗能同样有效改善中国患者的血脂和炎性标记物水平。     

瑞舒伐他汀对改善老年冠心病合并高脂血症患者的血脂水平及炎症因子含量的临床价值分析

目的：探究瑞舒伐他汀对改善老年冠心病合并高脂血症患者的血脂水平及炎症因子含量的临床价值。方法选择近年该院收治的43例老年冠心病合并高脂血症患者作为观察组行瑞舒伐他汀治疗,另选取同期收治同症患者43例作为对照组行阿托伐他汀治疗,观察对比两组治疗前后血脂水平及高敏C反应蛋白、白介素-6的变化。结果两组治疗后各血脂水平、各炎症因子含量均较治疗前得以明显控制,P<0.05;观察组治疗后各观察指标控制更为明显,P<0.05。结论对老年冠心病合并高脂血症给予瑞舒伐他汀治疗,可有效控制血脂水平,抑制炎症反应,可进一步改善临床预后。     

不同剂量瑞舒伐他汀钙对急性冠脉综合征非介入药物保守治疗患者的影响研究

目的：探讨不同剂量瑞舒伐他汀钙(10 mg和20 mg)对急性冠脉综姓合征(ACS)非PCI药物保守治疗患者血清铁蛋白、血脂水平及炎性因子的影响。方法将2010年1月—2014年6月该院收治的ACS非PCI药物保守治疗患者120例随机分为A、B、C 3组各40例,在给予吸氧、抗凝、扩张冠脉血管等治疗的基础上,A组口服瑞舒伐他汀钙10 mg,B组口服瑞舒伐他汀钙20 mg,C组口服阿托伐他汀钙20 mg,均1次/d。治疗前和治疗16周后抽取静脉血,观察3组治疗前后血清LDL、oxLDL、hsCRP水平。结果 A组治疗后血清铁蛋白、LDL、oxLDL、hsCRP分别为(189.27±11.15) ng/mL、(3.08±0.17) mmol/L、(45.17±1.63) mmol/L、(5.48±0.22) mmol/L;B组治疗后血清铁蛋白、LDL、oxLDL、hsCRP分别为(89.24±12.16) ng/mL、(2.51±0.31) mmol/L、(40.78±0.69) mmol/L、(4.34±0.27) mmol/L;C组治疗后血清铁蛋白、LDL、oxLDL、hsCRP分别为(195.78±13.65)ng/mL、(3.11±0.21) mmol/L、(45.24±1.71) mmol/L、(5.49±0.27) mmol/L。三组患者治疗16周后血清铁蛋白、血清LDL、oxLDL、hsCRP水平均较治疗前明显降低(P<0．05)。其中B组较A、C组降低明显(P<0．05),A组与C组比较有差异,但差异无统计学意义(P＞0．05)。结论 ACS非PCI药物保守治疗患者早期使用不同剂量瑞舒伐他汀钙能明显降低血清LDL、oxLDL、hsCRP水平,降低血脂水平,降低炎性因子,减轻炎性反应,可能起到稳定斑块、抗栓、改善预后的作用。     

瑞舒伐他汀对2型糖尿病视网膜病变患者血清PEDF、IL-6水平的影响

目的探讨瑞舒伐他汀对2型糖尿病视网膜病变(DR)患者血清PEDF、IL-6水平的影响。方法选取60例2型糖尿病视网膜病变患者,随机分为实验组(瑞舒伐他汀治疗)30例和空白对照组(仅常规降血糖治疗)30例,疗程为3个月。分析两组患者治疗前后血清PEDF、IL-6、TC、TG、LDL、HDL、FPG、2h PG、Hb A1c水平以及DR分期的变化情况。结果实验组血清IL-6、TC、TG、LDL、FPG、2h PG、Hb A1c水平及DR分期与治疗前比较明显下降,血清PEDF、HDL水平与治疗前比较明显升高,差异均有统计学意义(P<0.01)。空白对照组中FPG、2h PG、Hb A1c水平较治疗前明显下降(P<0.01),其余各指标与治疗前比较,差异均无统计学意义(P>0.05)。实验组治疗前后的差值(ΔPEDF、ΔIL-6、ΔDR分期、ΔTC、ΔTG、ΔLDL、ΔHDL)与对照组治疗前后的差值比较,差异均有统计学意义(P<0.01)。结论瑞舒伐他汀能显著降低DR患者血清IL-6水平,升高血清PEDF水平,从而延缓了DR患者的病情进展。