非诺贝特可降低高胆固醇血症兔的肿瘤坏死因子-α血清浓度及脂肪细胞分泌。

Fenofibrate reduces tumor necrosis factor-alpha serum concentration and adipocyte secretion of hypercholesterolemic rabbits.

作者信息

Zhao Shui-Ping, Wu Jie

机构信息

Department of Cardiology, The Second Xiangya Hospital of Central South University, middle Ren-Min road No. 86, Changsha, Hunan 410011, PR China.

出版信息

Clin Chim Acta. 2004 Sep;347(1-2):145-50. doi: 10.1016/j.cccn.2004.04.001.

DOI:10.1016/j.cccn.2004.04.001

PMID:15313152

Abstract

BACKGROUND

Tumor necrosis factor-alpha (TNF-alpha) is produced by cells of the macrophage-monocyte lineage and by adipocytes. It may provide the link between inflammation and atherosclerosis. The aim of this study was to evaluate the effect of fenofibrate on serum TNF-alpha concentration and TNF-alpha secretion by adipocytes from hypercholesterolemic rabbits.

METHODS

Ten male New Zealand white rabbits were fed with high-cholesterol diet for 8 weeks, and were randomly divided into two groups: (1) high cholesterol group: maintained cholesterol diet for 4 weeks; and (2) fenofibrate treated group: the same cholesterol diet supplemented with fenofibrate (30 mg/kg/day) for 4 weeks. Control group was fed with normal diet for 12 weeks. Subcutaneous adipose was collected for adipocytes culture. TNF-alpha concentrations in serum and adipocytes culture supernatant were measured by ELISA.

RESULTS

Rabbits fed with high-cholesterol diet showed higher serum levels of total cholesterol, low density lipoprotein cholesterol than those fed with normal diet (P<0.001). Fenofibrate treatment did not change serum lipid levels during the feeding period, but decreased high cholesterol diet-induced increases in body weight by 19% and serum TNF-alpha concentration by 44.7% in fenofibrate treated group compared with high cholesterol group (P<0.05). The decreased levels of TNF-alpha correlated with the weight loss (r=0.35, P<0.05). Fenofibrate (10 to 100 micromol/l) significantly reduced release of TNF-alpha in adipocytes (P<0.05). Meanwhile serum TNF-alpha concentration were significantly correlated with TNF-alpha secretion in adipocytes (r=0.51, P<0.05).

CONCLUSIONS

Our study indicated that fenofibrate reduced tumor necrosis factor-alpha serum concentration and adipocyte secretion of hypercholesterolemic rabbits. This effect of fenofibrate might contribute to its benefits on the prevention and treatment of atherosclerosis.

摘要

背景

肿瘤坏死因子-α（TNF-α）由巨噬细胞-单核细胞系细胞及脂肪细胞产生。它可能是炎症与动脉粥样硬化之间的联系纽带。本研究旨在评估非诺贝特对高胆固醇血症兔血清TNF-α浓度及脂肪细胞TNF-α分泌的影响。

方法

10只雄性新西兰白兔给予高胆固醇饮食8周，然后随机分为两组：（1）高胆固醇组：维持胆固醇饮食4周；（2）非诺贝特治疗组：在相同胆固醇饮食基础上补充非诺贝特（30毫克/千克/天）4周。对照组给予正常饮食12周。收集皮下脂肪用于脂肪细胞培养。采用酶联免疫吸附测定法（ELISA）检测血清及脂肪细胞培养上清液中TNF-α浓度。

结果

给予高胆固醇饮食的兔子血清总胆固醇、低密度脂蛋白胆固醇水平高于给予正常饮食的兔子（P<0.001）。非诺贝特治疗在喂养期间未改变血脂水平，但与高胆固醇组相比，非诺贝特治疗组高胆固醇饮食诱导的体重增加减少了19%，血清TNF-α浓度降低了44.7%（P<0.05）。TNF-α水平的降低与体重减轻相关（r=0.35，P<0.05）。非诺贝特（10至100微摩尔/升）显著降低脂肪细胞中TNF-α的释放（P<0.05）。同时，血清TNF-α浓度与脂肪细胞中TNF-α分泌显著相关（r=0.51，P<0.05）。