Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits

Cardiovascular disease is currently the leading cause of death in the West, and a search for factors limiting its occurrence is ongoing. Accumulated data indicate that quercetin, the major flavonol in the plant kingdom, may possess beneficial effects in atherosclerosis. The present study aimed at determination of effects of quercetin on hyperlipidemia and development of atherosclerotic lesions in two animal models, i.e. diet induced hyperlipidemia and aortic atherosclerosis, and in injured carotid artery in rabbits fed high-fat diet for 12 and 4 weeks, respectively. It was demonstrated that quercetin was effective in reducing serum triglycerides and cholesterol levels elevated by high-fat diet, after 12 weeks of the experiment. This activity was less prominent in the 4-week study in injured carotid artery rabbit model. Hypolipemic properties of the flavonoid were associated with the reduced formation of atherosclerotic plaques, both in the aorta (12-week study) as well as within injured carotid artery (4-week study) in high-fat diet-fed animals. The surface of the intima covered with atherosclerotic plaques in high-fat diet-fed rabbits was 24.6 +/- 33.1% in comparison to 0.7 +/- 1.3% (p < 0.05) in quercetin and high-fat diet supplemented animals. It is evident from the present study that quercetin possesses both hypolipemic and antiatherogenic properties.     

Influence of pioglitazone on experimental heart failure and hyperlipidemia in rats

Objectives:

To investigate the effect of pioglitazone on isoproterenol-induced heart failure and high-fructose diet-induced metabolic changes in rats.

Materials and Methods:

Three doses of pioglitazone (Pio – 3, 10, 30 mg/kg, po) were tested in male Wistar rats. In the Heart Failure (HF) group, treatment was followed by Isoproterenol (ISO) injection. The markers for HF, such as enzyme estimation, relative heart weight, and antioxidant status, were evaluated. In another group, metabolic disturbances were induced by High Fructose Diet (HFD). The influence of Pio treatment on Systolic Blood Pressure (SBP), serum glucose, Triglycerides (TG), Total Cholesterol (TC), and High-Density Lipoprotein (HDL)-cholesterol (HDL-c) were determined.

Results:

The results indicated that Pio at 10 mg increased significantly (P<0.05) the Lactate Dehydrogenase (LDH), Creatinine Kinase-MB (CK-MB), and antioxidant enzyme levels as compared to ISO. The high dose of Pio (30 mg) enhanced (P<0.05) Aspartate Transaminase (AST), Alanine Transaminase (ALT), Lipid Peroxidation (LPO),and relative heart weight in addition to increased LDH, CK-MB, and antioxidant enzyme activity. In the HFD group, a dose-dependent inhibitory effect was observed. Pio at 3 mg significantly reduced (P<0.05) elevated glycemia, TG, and SBP as compared to HFD rats. Further, the higher doses of Pio (10 and 30 mg) enhanced the inhibitory effect on glucose, TG, and SBP besides elevating the HDL-c levels. However, none of the tested doses of Pio significantly altered the TC level in HFD rats.

Conclusion:

The observations suggest that Pio exhibits anti-diabetic and anti-hypertensive effects and also partially corrected the hyperlipidemia, but the treatment augmented the cardiac damage associated with ISO. The antioxidant property of Pio appears to have a limited role in protecting the ISO-mediated heart damage.KEY WORDS: Anti-hyperlipidemia, anti-hypertensive, heart failure, pioglitazone     

高血脂症实验性动物模型的研究进展

高血脂症是目前医药界研究的热点,而实验性动物模型的制备在其研究中具有十分重要的作用.本文分别介绍了高血脂症先天性、化学物质诱导和转基因三种实验性动物模型的研究进展,为高血脂症研究提供参考.     

Effect of alfalfa meal on experimental hyperlipidemia]

The influence of alfalfa meal on hyperlipidemia induced by dietary cholesterol was examined and changes in serum total cholesterol (TC), triglycerides (TG) and non-esterified fatty acid (NEFA) in rabbits were recorded. Serum lipid levels of groups treated with alfalfa meal (R-1) as well as those not treated (R-2) were found to be elevated. TC of R-1 was lower than that of R-2. The inhibition effect of alfalfa meal on elevation of TC was apparent to a certain extent. The inhibition effect of alfalfa meal on elevation of TG and NEFA was greater than that of TC, thus it is suggested that alfalfa meal can be successfully utilized for experiments with lipids, when the rabbit is the experimental animal of choice. Effect of riboflavine-2,3,4,5-tetranicotinate (RN-4) on changes of TC, TG and NEFA in rats fed 1% cholesterol diet was also examined. RN-4 was mixed in the diet (0.5, 0.25 and 0.125%). TG levels in groups treated with RN-4 (Rt-2, Rt-3 and Rt-4) were lower than previously observed.     

益母草碱对实验性高脂血症大鼠的降脂作用

目的考察益母草碱对高脂饲料所诱导的高脂血症大鼠的血脂、血液流变学及微循环的影响。方法建立大鼠高脂血症模型,益母草碱按高、中、低剂量(10、5、2.5 mg.kg-1)ip给药4周,观察益母草碱对高脂血症大鼠的血脂、血液流变学以及肠系膜微循环的影响。结果益母草碱10、5 mg.kg-1可纠正高脂血症大鼠的血脂代谢紊乱,降低血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇的含量,降低血液流变学的各项异常指标,扩张微血管,改善微循环。结论益母草碱具有一定的降脂及改善微循环、血流变的作用。     

大鼠实验性高脂血症和高脂血症性脂肪肝模型研究

目的　建立高脂血症和高脂血症性脂肪肝实验动物模型。方法　采用SD大鼠 30只 ,随机分为对照组 (n =10 )和模型组 (n =2 0 )。对照组喂普通饲料 ,模型组喂普通饲料并给予脂肪乳剂灌胃 (10ml·kg-1)。动态观察一般情况和血清TG、TC、ALT、AST、MDA、SOD和肝脏TG、TC、MDA、SOD的变化 ,并行病理检查。结果　 1wk后 ,模型组血清TG和TC明显高于正常组 ,形成了高脂血症模型。 2wk后 ,随机处死模型中的 10只 ,与正常组相比 ,发现血清TG、TC、ALT和肝脏MDA均明显升高 ,而肝脏SOD则明显降低 ,病理显示有 2只轻度脂肪变性。在第 3wk处死剩余动物 ,发现肝指数、血清脂质、ALT、AST、MDA和肝脏TG、MDA与对照组相比显著升高 ,而SOD则明显降低 ;光镜下所见模型组均出现弥漫性肝细胞脂肪变性 ,并有炎症病灶。结论　通过 1wk脂肪乳剂的喂养 ,形成了高脂血症模型 ;继续给予脂肪乳剂 ,2wk后形成高脂血症性脂肪肝模型。     

Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe^–/– mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.     

大鼠实验性高脂血症五种造模方法的比较

目的选择理想的大鼠高脂血症动物模型造模方法。方法参考文献选取5种大鼠高脂血症动物模型配方,并将其制成乳剂给大鼠灌胃,分别在d10、d20、d30眼眶取血测定血清中胆固醇、低密度脂蛋白、高密度脂蛋白、甘油三酯的含量。结果其中四种高脂配方均不同程度的使大鼠血清中脂代谢紊乱,形成高血脂动物模型。结论在猪油和胆固醇的基础上同时加入胆盐和丙基硫氧嘧啶可以形成理想的大鼠高脂血症动物模型。     

菲参胶囊对实验性高脂血症大鼠血脂的影响

目的观察菲参胶囊对实验性高脂血症模型大鼠的降脂效果。方法取72只♂大鼠,普通饲料预饲7 d后取血,检测血清TC。根据血清中TC的水平随机均分为普饲组、模型组、美降之组及菲参胶囊高、中、低剂量组。除普饲组外,各组大鼠换用高脂饲料饲养。各组同时分别ig给予0.5%CMC-Na、美降之4 mg·kg-1、菲参胶囊原生药4、2、1 g·kg-1,qd,第28日晚禁饲不禁水,次日晨取血检测TG、TC、HDL-C、LDL-C,并计算TC/HDL-C。结果中、高剂量的菲参胶囊对大鼠实验性高脂血症有明显的防治作用,能呈剂量依赖性地降低高脂模型大鼠血清中的TC、TG、LDL-C、TC/HDL-C,对血清中的HDL-C则有升高或抑制其降低作用;低剂量菲参胶囊对实验性高脂血症大鼠模型也有调血脂作用。结论菲参胶囊对实验性高脂血症大鼠具有明显的降血脂作用。     

Inflammatory markers in hyperlipidemia: from experimental models to clinical practice

The role of inflammation in the development and progression of cardiovascular diseases is well established. Systemic inflammation and immune system play a central role in atherogenesis. The strong dependence of the atherosclerotic process on both a state of continuous low grade inflammation and the presence of lipid abnormalities gave impetus to research the association between hyperlipidemia and inflammatory status. In experimental and clinical studies, several inflammatory markers such as C-reactive protein, tumor necrosis factor-alpha, interleukin 6, nuclear factor kappa-β, adhesion molecules, serum amyloid-α, lipoprotein-associated phospholipase A2, fibrinogen and sCD40 ligand are associated with lipids level. Although, cholesterol lowering treatment has several important beneficial effects, there is still little clinical experience or data from clinical trials, in order to treat patients with hyperlipidemia and impaired inflammatory status.     

Effect of Feishen capsule on blood fat in experimental hyperlipidemia rats

目的 观察菲参胶囊对实验性高脂血症模型大鼠的降脂效果.方法 取72只♂大鼠,普通饲料预饲7d后取血,检测血清TC.根据血清中TC的水平随机均分为普饲组、模型组、美降之组及菲参胶囊高、中、低剂量组.除普饲组外,各组大鼠换用高脂饲料饲养.各组同时分别ig给予0.5％CMC-Na、美降之4 mg· kg-1、菲参胶囊原生药4、2、1 g·kg-1,qd,第28日晚禁饲不禁水,次日晨取血检测TG 、TC 、HDL -C 、LDL -C,并计算TC/HDL -C.结果 中、高剂量的菲参胶囊对大鼠实验性高脂血症有明显的防治作用,能呈剂量依赖性地降低高脂模型大鼠血清中的TC 、TG、LDL -C、TC/HDL -C,对血清中的HDL -C则有升高或抑制其降低作用;低剂量菲参胶囊对实验性高脂血症大鼠模型也有凋血脂作用.结论 菲参胶囊对实验性高脂血症大鼠具有明显的降血脂作用.     

短叶决明子对实验性高脂血症小鼠脂代谢的影响

目的:研究短叶决明子对实验性高脂血症模型小鼠脂代谢的影响,为开辟短叶决明新的药用部位提供试验依据。方法:喂饲高脂饲料8周建立高脂血症小鼠模型,试验第9周起将试验动物分为空白对照组、模型对照组、阳性对照组及短叶决明子高、中、低剂量组,灌胃给药6周。在试验第8,11,14周末,测定各组小鼠血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、谷丙转氨酶、谷草转氨酶的含量。结果:给药6周后,与模型对照组比较,短叶决明子各剂量组均能不同程度地降低小鼠血清中TC、TG、LDL-C含量,提高HDL-C含量,其中以短叶决明子高剂量作用效果最显著;短叶决明子对小鼠血清中ALT、AST的活性无显著的改善作用。结论:短叶决明子具有降低高脂血症模型小鼠血清中TC、TG的含量,提高HDL-C的含量,抑制LDL-C含量升高的作用,从而达到降低血脂水平的目的。     

The efficacy of substances with antihypoxic action in experimental hyperlipidemia]

Experiments on rats, guinea pigs and rabbits with hyperlipidemia induced by high-cholesterol diet have revealed that the specific antihypoxic drug oliphen has hypolipidemic effect which is least pronounced in oral GABA. Oliphen causes a significant increase in alpha-cholesterol (antiatherogenic lipoprotein cholesterol) decreased by hyperlipidemia. It is suggested that oliphen improves hepatic receptor-dependent uptake and atherogenic lipoprotein degradation.     

Sex and species differences in glutathione S-transferase activities

Glutathione S-transferases (GSTs) are one of the important enzymes in terms of not only drug metabolism but also physiological functions. The marked sex difference in GST activity has been found in rat and mouse liver cytosol, and such differences in rat liver are suggested to be primarily due to the differences in the subunit composition of GSTs in both sexes. In addition, GST activities of rat liver cytosol are known to be largely influenced by treatment with inducers such as phenobarbital and 3-methylcholanthrene and various hormones. GSTs are widely distributed in mammalian species, and multiplicity of GST has been demonstrated so far. The present review also describes multiple forms of GST from the viewpoint of enzymology and immunology.     

基于ICP-MS法筛选高脂血症患者与健康人血浆中差异金属元素

目的筛选出高脂血症对照组与正常对照组人血浆中差异金属元素。方法分别采用湿法消解与直接稀释法处理血浆样品,通过ICP-MS法对样品血浆进行多元素分析并对测定方法进行方法学考察。结果血浆中均检出Cu、As、Se、Cd、Zn、Mn、Cr、Fe、Pb、Li、V、Co、Ni、Mo、Hg等15种元素。平均回收率为91.81%~108.79%。该方法各元素检出限在1~93 ng·L~(-1)。结论该方法可以准确测量血浆样品中15种微量元素含量,依据含量通过使用SPSS 19.0(美国IBM公司)进行统计学分析,用SPSS 19.0中的独立分析t检验方法进行两组数据差异间的显著性检验,找到目标元素分别为Se、Cr、Zn、Fe、Cu。     

银曲胶囊对高脂血症大鼠血脂的影响

目的：观察银曲胶囊对实验性高脂血症大鼠血脂水平的影响。方法：大鼠用高脂饲料喂养2周以造成脂代谢紊乱模型,并根据体重或血清中总胆固醇水平随机分为模型组、血脂康组和银曲胶囊大、中、小3个剂量组（0.5、1.0、2.0g/kg）。采用预防和治疗给药,通过测定大鼠血清中总胆固醇、甘油三酯等水平,观察银曲胶囊对实验性大鼠血脂的影响。结果：在预防和治疗实验中,银曲胶囊大、中、小3个剂量组血清中总胆固醇、甘油三酯、低密度脂蛋白、极低密度脂蛋白等水平与模型组比较均有一定程度降低,高密度脂蛋白水平略升高（P〈0.05或P〈0.01）。结论：银曲胶囊对实验性高脂血症大鼠有一定的防治作用。     

一种小鼠高脂血症新模型的建立

目的建立高脂血症实验动物模型新型方法。方法30只小鼠随机分为空白对照组、阳性对照组及模型组。空白对照组喂饲标准饲料,阳性对照组喂饲高脂饲料;模型组饲以标准饲料和牛奶,30d后检测血清和肝脏胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及肝脏指数(LI),光镜观察肝脏病理变化。结果与空白组相比,模型组LI及血液和血清中TC、TG、LDL-C明显升高,而HDL-C明显降低。光镜下模型组肝脏均出现弥漫性肝细胞脂肪变性和炎症病灶。结论小鼠喂饲30d标准饲料和牛奶,可建立理想的高脂血症模型。