Proia A, McNamara D J, Edwards K D, Ahrens E H
Proc Natl Acad Sci U S A. 1979 Sep;76(9):4654-7. doi: 10.1073/pnas.76.9.4654.
Studies were undertaken to determine the effect of portacaval anastomosis on cholesterol homeostasis in rats fed sucrose/lard under conditions of normal body growth. Four to 6 weeks after portacaval shunt surgery, we found decreases in plasma cholesterol and triglyceride concentrations, total liver weight, and hepatic microsomal protein concentration. Measurements oof hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained. Decreased reductase activity in shunted rats was not due to an altered Km for D-HMG-COA, nor was an enzyme inhibitor found in the livers of the portacaval shunt animals. Sterol balance measurements in rats with shunts showed a 22% decrease in whole body cholesterol synthesis rate compared to controls. These metabolic studies, coupled with postmortem data, showed diminished bile acid synthesis, unchanged fecal neutral steroid excretion, and decreased net tissue accumulation of cholesterol during growth. The decreased whole body cholesterol synthesis rate ultimately led to a diminished total carcass cholesterol concentration in the rats with shunts.
开展了多项研究，以确定在正常身体生长条件下，门腔静脉吻合术对喂食蔗糖/猪油的大鼠胆固醇稳态的影响。门腔静脉分流手术后4至6周，我们发现血浆胆固醇和甘油三酯浓度、肝脏总重量以及肝微粒体蛋白浓度均下降。对肝脏3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（EC 1.1.1.34）活性的测量显示，门腔静脉分流大鼠的比活性和肝脏总活性均下降，但该酶的昼夜节律依然存在。分流大鼠中还原酶活性的降低并非由于对D-HMG-COA的米氏常数（Km）改变，在门腔静脉分流动物的肝脏中也未发现酶抑制剂。对分流大鼠的甾醇平衡测量显示，与对照组相比，全身胆固醇合成率降低了22%。这些代谢研究与尸检数据相结合，表明胆汁酸合成减少、粪便中性类固醇排泄不变，且生长期间胆固醇的净组织积累减少。全身胆固醇合成率的降低最终导致分流大鼠的胴体总胆固醇浓度降低。
