Qiu Dong Ni, Shang Quan, Sun Da Yu, Ding Wei Qun, Luo Zhong Guang, Chen Jian, Jiang Wei Ru, Huang Jian Ping, Jiang Xiao Yun
Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
GI Lab VA Medical Center, East Orange, New Jersey, USA.
J Dig Dis. 2017 Feb;18(2):107-114. doi: 10.1111/1751-2980.12445.
Cholestyramine (CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models.
New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO-treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase ( CYP7A1 ), small heterodimer partner ( SHP ), bile salt export pump ( BSEP ), ileal bile acid-binding protein ( IBABP ) and LDL receptor ( LDL-R ) mRNA expressions were assessed by real-time polymerase chain reaction. CYP7A1 activity was also determined.
CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL-R mRNA expressions, but decreased hepatic SHP and BSEP gene expressions.
CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis.
考来烯胺（CHO）作为一种胆汁酸螯合交换树脂，已被广泛用于治疗高胆固醇血症。本研究旨在探讨CHO在动物模型中如何调节血清胆固醇含量和胆汁酸水平。
将新西兰白兔随机分为对照组（给予蒸馏水）和CHO治疗组（给予CHO溶液1 g/kg，每日一次，持续2周）。为评估胆汁酸池大小，每组选取5只兔子建立胆汁瘘。测定血清胆固醇水平、胆汁和粪便胆汁排出量。通过实时聚合酶链反应评估肝脏胆固醇7α-羟化酶（CYP7A1）、小异源二聚体伴侣（SHP）、胆盐输出泵（BSEP）、回肠胆汁酸结合蛋白（IBABP）和低密度脂蛋白受体（LDL-R）mRNA表达。同时测定CYP7A1活性。
CHO治疗使血清胆固醇水平降低了12.1%。虽然CHO未改变胆汁酸池大小和胆汁胆汁酸排出量，但显著增加了粪便胆汁酸排出量。有趣的是，CHO还显著增加了CYP7A1的表达和活性，以及IBABP和LDL-R mRNA表达，但降低了肝脏SHP和BSEP基因表达。
CHO显著改变兔肠道和肝脏组织中的胆汁酸和胆固醇含量，下调负责胆固醇稳态的基因。
