Hassan A S
University of Illinois, Department of Veterinary Biosciences, Urbana 61801.
Biochim Biophys Acta. 1988 Nov 25;963(2):131-8. doi: 10.1016/0005-2760(88)90274-3.
The objective of this study was to examine the effect of chronic inhibition of glutathione (GSH) biosynthesis on cholesterol and bile acid metabolism in rats. Male Sprague-Dawley rats, weighing between 60 and 65 g, were randomly assigned to one of two groups and allowed a 1-week adaptation period to a 6 a.m.-6 p.m. light cycle. Food and water were available ad libitum. Following the adaptation period, 1 group was given a solution of 30 mM DL-buthionine sulfoximine (BSO, an inhibitor of GSH biosynthesis) in saline, while the other group received saline only. All studies were carried out during, or at the end of the second week of BSO treatment. While body weight was minimally affected by BSO treatment, liver weight (% of body weight) was significantly greater in the BSO group (control 4.8 +/- 0.2 vs. BSO 5.2 +/- 0.3; P less than 0.05). The increase in liver weight, however, was not associated with a change in the specific content of cytochrome P-450. Even though fecal output (g/100 g per day) was significantly greater in the BSO group (control 2.4 +/- 0.1 vs. BSO 2.7 +/- 0.3; P less than 0.05), it was not commensurate with an increase in fecal bile acids and neutral sterols. In fact, fecal bile acid excretion (mg/100 g per day) was significantly reduced in the BSO group (control 9.0 +/- 2.0 vs. BSO 6.2 +/- 0.9; P less than 0.05), a finding consistent with a significant reduction in bile acid pool size (mg/100 g) in that group (control 23.1 +/- 1.9 vs. BSO 14.3 +/- 4.8; P less than 0.05). Hepatic GSH content (mumol/g) and cholesterol 7 alpha-hydroxylase activity (pmol/mg per min) were assayed at two time points: 12-2 a.m. (mid-dark point) and 12-2 p.m. (mid-light point). At mid-dark point, BSO-treated animals had a significantly lower hepatic GSH content (control 4.5 +/- 0.3 vs. BSO 0.6 +/- 0.3; P less than 0.05) and a significantly lower cholesterol 7 alpha-hydroxylase activity (control 33.5 +/- 1.3 vs. BSO 14.7 +/- 3.9; P less than 0.05). At mid-light point, hepatic GSH content in the two groups was similar to that at mid-dark point. While cholesterol 7 alpha-hydroxylase activity in both groups was significantly lower (P less than 0.05) at mid-light point relative to that at mid-dark point, there was no difference between the two groups in cholesterol 7 alpha-hydroxylase activity at mid-light point.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是检测长期抑制谷胱甘肽（GSH）生物合成对大鼠胆固醇和胆汁酸代谢的影响。体重在60至65克之间的雄性Sprague-Dawley大鼠被随机分为两组，在上午6点至下午6点的光照周期下有1周的适应期。食物和水可随意获取。适应期过后，一组给予含30 mM DL-丁硫氨酸亚砜胺（BSO，一种GSH生物合成抑制剂）的生理盐水溶液，而另一组仅接受生理盐水。所有研究均在BSO治疗的第二周期间或结束时进行。虽然BSO治疗对体重影响极小，但BSO组的肝脏重量（占体重的百分比）显著更高（对照组4.8±0.2 vs. BSO组5.2±0.3；P＜0.05）。然而，肝脏重量的增加与细胞色素P-450的比含量变化无关。尽管BSO组的粪便排出量（克/100克/天）显著更高（对照组2.4±0.1 vs. BSO组2.7±0.3；P＜0.05），但这与粪便胆汁酸和中性固醇的增加并不相称。事实上，BSO组的粪便胆汁酸排泄量（毫克/100克/天）显著降低（对照组9.0±2.0 vs. BSO组6.2±0.9；P＜0.05），这一发现与该组胆汁酸池大小（毫克/100克）的显著降低一致（对照组23.1±1.9 vs. BSO组14.3±4.8；P＜0.05）。在两个时间点测定肝脏GSH含量（微摩尔/克）和胆固醇7α-羟化酶活性（皮摩尔/毫克/分钟）：凌晨12点至2点（黑暗中点）和中午12点至下午2点（光照中点）。在黑暗中点，经BSO处理的动物肝脏GSH含量显著更低（对照组4.5±0.3 vs. BSO组0.6±0.3；P＜0.05），胆固醇7α-羟化酶活性也显著更低（对照组33.5±1.3 vs. BSO组14.7±3.9；P＜0.05）。在光照中点，两组的肝脏GSH含量与黑暗中点时相似。虽然相对于黑暗中点，两组在光照中点时胆固醇7α-羟化酶活性均显著更低（P＜0.05），但在光照中点时两组的胆固醇7α-羟化酶活性没有差异。（摘要截选至400字）
