普罗布考长期给药对大鼠甘油三酯周转率的影响。

Effect of long-term administration of probucol on triglyceride turnover in rats.

作者信息

Yoshino G, Matsushita M, Maeda E, Nagata K, Naka Y, Murata Y, Hirano T, Kazumi T

机构信息

Second Department of Internal Medicine, Kobe University School of Medicine, Japan.

出版信息

Coron Artery Dis. 1994 Jan;5(1):67-72. doi: 10.1097/00019501-199401000-00009.

DOI:10.1097/00019501-199401000-00009

PMID:8136934

Abstract

BACKGROUND

Our previous observation revealed that probucol, a well known cholesterol-lowering drug, can improve impaired catabolism of plasma triglyceride in streptozotocin-diabetic rats without reducing plasma glucose. The present study was conducted using Triton WR1339 and endogenously radiolabeled lipoproteins in order to examine the mechanisms whereby the drug can stimulate triglyceride removal from the circulation in rats independent of glucose metabolism.

METHODS

The short- and long-term effects of probucol on triglyceride turnover were examined in rats. Male Wistar rats received a diet containing probucol (1%) for 2 weeks and 4 months. Triglyceride turnover was estimated in rats using Triton WR1339.

RESULTS

After 2 weeks of probucol administration, triglyceride and cholesterol concentrations in plasma and in the very-low-density lipoprotein (VLDL) fraction were suppressed slightly but significantly in the probucol-administered rats compared with standard chow-fed control rats. However, triglyceride secretion rates were similar in the two groups. Probucol-administered rats showed markedly suppressed triglyceride concentration in plasma and the VLDL fraction compared with chow-fed control rats after 4 months of administration. However, triglyceride secretion rate was significantly increased in rats given probucol. The radioisotope experiment revealed that probucol-administered rats can remove VLDLs (lipoproteins either from probucol-administered or control rats) from their system faster than normal rats and that probucol-containing VLDL can be removed from the circulation of both groups of rats more rapidly than normal VLDL. Therefore, probucol-administered rats as well as probucol-containing VLDL (lipoprotein from probucol-administered rats) are responsible for accelerated catabolism of VLDL-triglyceride.

CONCLUSION

No significant differences in the lipid composition of newly-secreted VLDL particles between control rats and those given probucol were noted after Triton injection. The precise mechanism behind increased triglyceride secretion rate in rats after long-term administration of probucol is not known. However, we concluded from the present data that long-term administration of probucol results in markedly accelerated VLDL-triglyceride turnover without affecting lipid composition of newly secreted VLDL particles in normal rats.

摘要

背景

我们之前的观察结果显示，普罗布考（一种知名的降胆固醇药物）可改善链脲佐菌素诱导的糖尿病大鼠血浆甘油三酯分解代谢受损的情况，且不会降低血糖水平。本研究使用 Triton WR1339 和内源性放射性标记的脂蛋白进行，以探究该药物在不依赖葡萄糖代谢的情况下刺激大鼠从循环中清除甘油三酯的机制。

方法

研究了普罗布考对大鼠甘油三酯周转率的短期和长期影响。雄性 Wistar 大鼠食用含普罗布考（1%）的饲料 2 周和 4 个月。使用 Triton WR1339 评估大鼠的甘油三酯周转率。

结果

给予普罗布考 2 周后，与标准饲料喂养的对照大鼠相比，给予普罗布考的大鼠血浆和极低密度脂蛋白（VLDL）部分中的甘油三酯和胆固醇浓度略有但显著降低。然而，两组的甘油三酯分泌率相似。给予普罗布考 4 个月后，与正常饲料喂养的对照大鼠相比，给予普罗布考的大鼠血浆和 VLDL 部分中的甘油三酯浓度明显降低。然而，给予普罗布考的大鼠甘油三酯分泌率显著增加。放射性同位素实验表明，给予普罗布考的大鼠从其体内清除 VLDL（来自给予普罗布考或对照大鼠的脂蛋白）的速度比正常大鼠快，且含普罗布考的 VLDL 比正常 VLDL 能更快地从两组大鼠的循环中清除。因此，给予普罗布考的大鼠以及含普罗布考的 VLDL（来自给予普罗布考大鼠的脂蛋白）是 VLDL - 甘油三酯分解代谢加速的原因。

结论

注射 Triton 后，对照大鼠和给予普罗布考的大鼠新分泌的 VLDL 颗粒的脂质组成无显著差异。长期给予普罗布考后大鼠甘油三酯分泌率增加背后的确切机制尚不清楚。然而，根据目前的数据我们得出结论，长期给予普罗布考可导致正常大鼠的 VLDL - 甘油三酯周转率显著加快，而不影响新分泌的 VLDL 颗粒的脂质组成。