Karasu C
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Turkey.
Exp Clin Endocrinol Diabetes. 1998;106(3):189-96. doi: 10.1055/s-0029-1211975.
The effects of acute probucol treatment on plasma lipids, lipid peroxides and vasomotor activity and structure of aorta were investigated in long-term streptozotocin (STZ)-diabetic rats. Treatment with probucol (300 mg/kg/day, i.o.) was initiated 10 weeks after the induction of diabetes and was continued for 2 or 3 weeks. Plasma cholesterol, triglyceride and thiobarbituric acid reactive substance (TBARS) levels were markedly increased in untreated diabetic rats, however, probucol treatment led to significant reductions in all of these characteristics in diabetic animals. Plasma glucose and insulin levels were similar between untreated and probucol-treated diabetic groups. STZ-diabetes impaired morphological integrity of aorta and caused significantly increase in contractile response to noradrenaline (NA). The percentage of endothelial response (PER), which was calculated in terms of the NA-induced maximum contractile response of aorta, as index of endothelial function, significantly decreased in untreated diabetic rats. Treatment of diabetic rats with probucol resulted in partial restorations in endothelial function and NA-induced contraction in aorta, whereas morphological changes were not affected. These observations suggest that the ability of acute probucol treatment to restore vessel functions may have important implications regarding the pathogenesis and treatment of diabetes and its complications.
在长期链脲佐菌素(STZ)诱导的糖尿病大鼠中,研究了急性普罗布考治疗对血脂、脂质过氧化物以及主动脉血管舒缩活性和结构的影响。糖尿病诱导10周后开始用普罗布考(300毫克/千克/天,口服)治疗,并持续2或3周。未治疗的糖尿病大鼠血浆胆固醇、甘油三酯和硫代巴比妥酸反应性物质(TBARS)水平显著升高,然而,普罗布考治疗使糖尿病动物的所有这些指标均显著降低。未治疗和普罗布考治疗的糖尿病组之间血浆葡萄糖和胰岛素水平相似。STZ糖尿病损害了主动脉的形态完整性,并导致对去甲肾上腺素(NA)的收缩反应显著增加。作为内皮功能指标,根据主动脉对NA诱导的最大收缩反应计算的内皮反应百分比(PER)在未治疗的糖尿病大鼠中显著降低。用普罗布考治疗糖尿病大鼠可部分恢复主动脉的内皮功能和NA诱导的收缩,而形态学变化未受影响。这些观察结果表明,急性普罗布考治疗恢复血管功能的能力可能对糖尿病及其并发症的发病机制和治疗具有重要意义。