非诺贝特胶囊(Ⅱ)和脂必泰胶囊治疗高脂血症疗效观察

目的 观察并分析比较非诺贝特胶囊(Ⅱ)和脂必泰胶囊在治疗高脂血症的方面的临床效果.方法 将我院在2011年1月至2012年1月收治的158例高脂血症患者随机分为:非诺贝特胶囊(Ⅱ)组79例和脂必泰组79例,对比分析2组患者的整体有效率以及各项指标.结果 非诺贝特胶囊(Ⅱ)组整体有效率为91.1%(72/79),脂必泰组整体有效率为92.4%(73/79),2组患者在整体有效率以及各项指标方面的差异无统计学意义(P>0.05),2组患者在治疗期间均出现了不良反应,但在治疗过程中逐渐消失.结论 非诺贝特胶囊(Ⅱ)和脂必泰胶囊在治疗高脂血症方面均有着显著的疗效,并且药物副作用小,用药安全性较好.     

Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia.

AIMS: To examine the efficacy and safety of coadministered ezetimibe (EZE) with fenofibrate (FENO) in patients with mixed hyperlipidaemia. METHODS AND RESULTS: This was a multicentre, randomized, double-blind, placebo-controlled, parallel arm trial in patients with mixed hyperlipidaemia [LDL-cholesterol (LDL-C), 3.4-5.7 mmol/L (2.6-4.7 mmol/L for patients with type 2 diabetes); triglycerides (TG), 2.3-5.7 mmol/L] and no history of coronary heart disease (CHD), CHD-equivalent disease (except for type 2 diabetes), or CHD risk score>20%. A total of 625 patients was randomized in a 1:3:3:3 ratio to one of four daily treatments for 12 weeks: placebo; EZE 10 mg; FENO 160 mg; FENO 160 mg plus EZE 10 mg (FENO+EZE). The primary endpoint compared the LDL-C lowering efficacy of FENO+EZE vs. FENO alone. LDL-C, non-HDL-cholesterol (non-HDL-C), and apolipoprotein B were significantly (P<0.001) reduced with FENO+EZE when compared with FENO or EZE alone. TG levels were significantly decreased and HDL-C was significantly increased with FENO+EZE and FENO treatments when compared with placebo (P<0.001). Coadministration therapy reduced LDL-C by 20.4%, non-HDL-C by 30.4%, TG by 44.0%, and increased HDL-C by 19.0%. At baseline, >70% of all patients exhibited the small, dense LDL pattern B profile. A greater proportion of patients on FENO+EZE and FENO alone treatments shifted from a more atherogenic LDL size pattern to a larger, more buoyant, and less atherogenic LDL size pattern at study endpoint than those on placebo or EZE. All three active therapies were well tolerated. CONCLUSION: Coadministration of EZE with FENO provided a complementary efficacy therapy that improves the atherogenic lipid profile of patients with mixed hyperlipidaemia.     

多烯磷脂酰胆碱联合二甲双胍和非诺贝特治疗NAFLD患者血清Pygo2和血脂水平变化*

目的 探讨应用多烯磷脂酰胆碱联合二甲双胍和非诺贝特治疗非酒精性脂肪性肝病(NAFLD)患者血清人尾肢同源蛋白2(Pygo2)和血脂水平的变化。方法 2015年3月 ~2019年6月我院收治的NAFLD患者64例,被随机分为对照组32例和观察组32例。给予对照组二甲双胍片和非诺贝特胶囊口服治疗,观察组在此治疗的基础上加用多烯磷脂酰胆碱口服,两组均连续治疗12周。采用放射免疫分析法检测血清透明质酸(HA)和层黏蛋白(LN)水平,采用ELISA法检测血清Pygo2、高迁移率族蛋白B1(HMGB1)和白细胞介素-17(IL-17)。结果 在治疗结束时,观察组血甘油三酯(TG)水平为(1.8±0.1)mmol/L,显著低于对照组【(2.7±0.4)mmol/L,P＜0.05】,总胆固醇(TC)水平为(4.6±0.4)mmol/L,显著低于对照组【(5.8±0.6)mmol/L,P＜0.05】,而血高密度脂蛋白胆固醇(HDL-C)水平为(1.9±0.5)mmol/L,显著高于对照组【(1.5±0.4)mmol/L,P＜0.05】;观察组血清丙氨酸氨基转移酶(ALT) 水平为(28.4±3.2)U/L,显著低于对照组【(35.9±4.1)U/L,P＜0.05】,天冬氨酸氨基转移酶(AST) 水平为(22.1±2.0)U/L,显著低于对照组【(32.6±3.4)U/L,P＜0.05】,血清HMGB1 水平为(13.7±1.5)μg/L,显著低于对照组【(20.2±2.4)μg/L,P＜0.05】,IL-17水平为(75.6±7.8)pg/mL,显著低于对照组【(90.7±10.2)pg/mL,P＜0.05】;观察组血清HA水平为(84.5±9.2)mg/L,显著低于对照组【(117.6±10.3)mg/L,P＜0.05】, LN水平为(91.2±10.2)μg/L,显著低于对照组【(108.7±11.3)μg/L,P＜0.05】,Pygo2水平为(37.5±4.1)μg/L,显著低于对照组【(42.4±5.0)μg/L,P＜0.05】。结论 在运动和饮食控制的基础上,应用多烯磷脂酰胆碱联合二甲双胍和非诺贝特治疗可显著改善NAFLD患者脂代谢,抑制炎症反应和肝纤维化程度,短期临床疗效显著。     

经皮冠状动脉介入治疗后再狭窄的实验研究--非诺贝特对内皮细胞增殖及凋亡的干预作用

目的建立再狭窄内皮细胞模型并探讨非诺贝特对经皮冠状动脉治疗后再狭窄的防治作用。方法体外培养人脐静脉内皮细胞(HUVECs),分为:(1)正常对照组,(2)溶血卵磷脂(LPC)组,(3)低浓度非诺贝特组(10μmol/L),(4)中浓度非诺贝特组(50μmol/L),(5)高浓度非诺贝特组(100μmol/L)。分别观测内皮细胞增殖、凋亡及上清液一氧化氮(NO)浓度的的变化。结果与正常对照组比较,LPC抑制内皮细胞增殖,促进细胞凋亡,降低NO浓度。非诺贝特可干预LPC对内皮细胞的作用,使内皮细胞增殖增强,细胞凋亡减少,NO浓度升高。结论非诺贝特可改善LPC对HUVECs的影响,使内皮细胞增殖增强,凋亡减少,升高NO浓度,从而起到防治PCI后再狭窄的作用。     

非诺贝特对脂肪组织凝血和纤溶因子表达的影响

目的:探讨动脉粥样硬化兔脂肪组织组织因子(TF)和Ⅰ型纤溶酶原激活物抑制剂(PAI-1)表达及非诺贝特对其的影响。方法:15只兔随机等分为3组,正常组予普通饲料喂养12周,动脉粥样硬化组给予高胆固醇饮食12周,非诺贝特组在高胆固醇饮食8周后加非诺贝特30mg·kg-1·d-1干预4周。实验第12周末取兔皮下脂肪组织,RT-PCR测定脂肪组织TF和PAI-1mRNA表达;同时采血10ml,分离血浆,用ELISA方法测定血浆TF活性,发色底物法测定血浆PAI-1活性。结果:高胆固醇饮食可显著升高血清总胆固醇(TC)(P<0·05),血清三酰甘油(TG)无明显升高;加用非诺贝特治疗4周,TC和TG均无明显改变。动脉粥样硬化组脂肪组织TF和PAI-1mRNA表达(分别为1.15±0.01和1.20±0.01)明显高于正常组(分别为1.03±0.01和1.10±0.01),均P<0·01;血浆TF和PAI-1活性[分别为(74.4±28.8)ng/L和(15.6±1.9)×103AU/L]较正常组[分别为(33.1±10.7)ng/L和(6.9±0.9)×103AU/L]增高(P<0·05)。非诺贝特组TF和PAI-1mRNA表达(分别为1.02±0.01和1.06±0.01)、血浆TF和PAI-1活性[分别为(40.3±12.2)ng/L和(7.5±1.5)×103AU/L]均有显著降低(P<0.01或P<0·05)。结论:动脉粥样硬化兔脂肪组织表达TF和PAI-1增加,活性增强,非诺贝特能抑制动脉粥样硬化兔脂肪组织TF和PAI-1的表达及活性,提示非诺贝特可能具有独立于降脂作用之外的抗血栓作用。     

A comparative study of anti-inflammatory and antidyslipidemic effects of fenofibrate and statins on rheumatoid arthritis

Abstract

We prospectively compared the anti-inflammatory and antidyslipidemic effects of fenofibrate and statins in rheumatoid arthritis (RA) patients. Forty-four RA patients [male (M) = 7, female (F) = 37] with dyslipidemia were enrolled in this 6-month study and randomly allocated to the fenofibrate (2 M + 21 F = 23) or statins (5 M + 16 F = 21) group. We measured blood chemistry (serum lipid profile, sugar, urate, and γ-glutamyl transpeptidase) and blood pressure 2 h after breakfast. Visual analog scale (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and prednisolone (PSL) dosage were also recorded immediately before and after the study. Fenofibrate, but not statins, significantly decreased serum levels of total cholesterol, low-density lipoprotein–cholesterol, and triglycerides (all p < 0.05). A significant improvement in VAS was observed in both the fenofibrate group (49.1 ± 24.7 → 14.7 ± 11.2; p < 0.0001) and the statins group (47.4 ± 29.7 → 20.2 ± 16.5; p < 0.001). PSL dosage significantly decreased only in the fenofibrate group (3.58 ± 2.68 → 2.00 ± 2.22 mg/day; p < 0.01). Significant correlation was observed between ?VAS and ?CRP in the fenofibrate group (p < 0.05). Fenofibrate showed more anti-inflammatory and antidyslipidemic activity than statins in RA.     

考来烯胺调脂作用临床观察

原发性高脂血症２５８例采取随机、双盲法分成考来烯胺组（１６４例）与非诺贝特组（对照组）（９４例）。疗程８周。考来烯胺治疗结束后测血脂分别下降ＴＣ２５％、ＴＣ／ＨＤＬ－Ｃ３７％、ＬＤＬ４２％、ＡｐｏＢ２７％、Ｌｐ（ａ）２４％，ＨＤＬ－Ｃ、ＡｐｏＡ分别增高１７％、１０％，自身与组间对照Ｐ均＜０．０１。治疗２周后，总有效率考来烯胺组８３．５％，非诺贝特组６８．８％，两组８周后分别为８９．６％、７６％。两组间Ｐ均＜０．０１。显示考来烯胺有良好调脂作用，优于非诺贝特，值得推广应用。