探討Sildenafil類緣物對大鼠肝臟一氧化氮生成及氧化壓力之影響

The Effects of Sildenafil Analogue on the Generation of Nitric Oxide and Oxidative Stress in Rat Liver

本實驗目的以sildenafil類緣物（分子量為484）為材料，探討其對大鼠肝臟一氧化氮（NO）合成、脂質代謝、氧化壓力（TBARS）及肝功能（GPT、GOT）之影響。32隻八週大Sprague-Dawley（SD）雄性大鼠隨機分為四組（n=8），（1）Control組-C組，（2）低劑量組（36 mg sildenafil類緣物／Kg diet）-L組，（3）中劑量組（90 mg sildenafil類緣物／Kg diet）-M組及（4）高劑量組（180 mg sildenafil類緣物/Kg diet）-H組，並採用AIN-93G飼料配方，飼料及飲水採自由進食。在飼養30天後，以CO2將其犧牲；並進行樣品分析。結果發現低劑量的sildenafil類緣物具有較佳調控血脂的作用；大鼠肝臟NO的濃度隨著sildenafil類緣物劑量的增加而增加，三組實驗組大鼠肝臟的TBARS和GOT顯著高於C組大鼠；從本實驗的結果推論，此sildenafil類緣物會促進實驗大鼠肝臟的NO的合成，NO濃度上升對肝臟可能會造成氧化性傷害而使GPT、GOT昇高。

The aim of this study was to investigate the effects of sildenafil analogue on the NO generation, oxidative stress, lipid metabolism, and liver function in the rat. Thirty-two male Sprague-Dawley （SD） rats （10-week-old） were randomly divided into four groups （n = 8）, （1） Control group （C group） （2） High dose group （180 mg sildenafil analogue /Kg diet, H group） （3） Middle dose group （90 mg sildenafil analogue /Kg diet, M group） （4） Low dose group （36 mg sildenafil analogue /Kg/diet, L group）. The rats were fed an AIN-93G diets with or without sildenafil analogue. After 30 days, the rats were sacrificed and samples were analyzed. The concentrations of nitric oxide in the liver were increased with the increasing of the dose of the sildenafil analogue supplemented. The concentrations of TC and TG in the plasma of the rats in L and M group were decreased significantly when compared with the rat in C group. The concentrations of TBARS and GOT of the rats in the experimental groups were significant higher than the rats in C group. The results from this study indicate that additional supplement of this new sildenafil analogue may increase the NO production in rats. Nitric oxide then increased the oxidative stress in rats liver and may impaired liver cells function.