Hassan A S, Hackley J J, Johnson L L
Atherosclerosis. 1985 Nov;57(2-3):139-48. doi: 10.1016/0021-9150(85)90027-9.
Timed pregnant (8 days) Sprague-Dawley rats were fed ground stock diet (CON) or ground stock diet with 4% cholestyramine (CTR) until day 20 of gestation. Animals in both groups gained weight equally well during the study period (CON (n = 7), 308 +/- 7 g; CTR (n = 6), 315 +/- 7 g, mean +/- SEM). At the end of the study period, plasma cholesterol in the CTR group was significantly greater than that in the control group (CON n = 7, 91 +/- 4 mg/dl; CTR (n = 6), 108 +/- 5 mg/dl, P less than 0.05). The fecal excretion of both neutral steroids and bile acids, studied for 3 days between days 15 and 18 of gestation, was significantly enhanced by CTR treatment. (Neutral steroids: CON, 3.9 +/- 0.3; CTR, 10.4 +/- 0.3, P less than 0.05. Bile acids: CON, 7.6 +/- 0.4; CTR, 25.8 +/- 1.7, P less than 0.05, mg/100 g body wt/day). Bile acid pool size, measured at day 20 of gestation, however, was not significantly different. Consistent with these results was the finding that hepatic cholesterol 7 alpha-hydroxylase activity (the rate-limiting enzyme of bile acid biosynthesis) measured at day 20 of gestation was significantly enhanced by CTR treatment (CON (n = 4), 14.7 +/- 1.7; CTR (n = 4), 34.8 +/- 3.3, pmoles/mg/min, P less than 0.05). The atypical finding of hypercholesterolemia, despite the CTR-induced enhanced turnover of cholesterol, may be due to changes in the homeostatic mechanisms of cholesterol and bile acid metabolism during pregnancy.
将妊娠8天的斯普拉格-道利大鼠分为两组，一组喂食基础饲料（CON），另一组喂食添加4%消胆胺的基础饲料（CTR），直至妊娠第20天。在研究期间，两组动物体重增加情况相同（CON组（n = 7），体重增加308±7克；CTR组（n = 6），体重增加315±7克，均值±标准误）。研究期末，CTR组血浆胆固醇水平显著高于对照组（CON组（n = 7），91±4毫克/分升；CTR组（n = 6），108±5毫克/分升，P<0.05）。在妊娠第15天至18天期间，对中性类固醇和胆汁酸的粪便排泄量进行了为期3天的研究，结果显示CTR处理显著增加了二者的排泄量（中性类固醇：CON组，3.9±0.3；CTR组，10.4±0.3，P<0.05。胆汁酸：CON组，7.6±0.4；CTR组，25.8±1.7，P<0.05，毫克/100克体重/天）。然而，在妊娠第20天测量的胆汁酸池大小并无显著差异。与这些结果一致的是，在妊娠第20天测量发现，CTR处理显著增强了肝脏胆固醇7α-羟化酶活性（胆汁酸生物合成的限速酶）（CON组（n = 4），14.7±1.7；CTR组（n = 4），34.8±3.3，皮摩尔/毫克/分钟，P<0.05）。尽管CTR导致胆固醇周转加快，但出现高胆固醇血症这一非典型发现，可能是由于妊娠期间胆固醇和胆汁酸代谢的稳态机制发生了变化。
