Ngo Sock Emilienne Tudor, Mayer Gaétan, Lavoie Jean-Marc
Laboratory of molecular cell biology, Montreal heart institute, Montréal (QC) Canada.
Department of medicine, Faculté de médecine, Université de Montréal, Montréal (QC) Canada.
PLoS One. 2016 Jul 21;11(7):e0159550. doi: 10.1371/journal.pone.0159550. eCollection 2016.
The purpose of this study was to investigate the effects of three weeks of rosuvastatin (Ros) treatment alone and in combination with voluntary training (Tr) on expression of genes involved in cholesterol metabolism (LDLR, PCSK9, LRP-1, SREBP-2, IDOL, ACAT-2 and HMGCR) in the liver of eight week-old ovariectomized (Ovx) rats. Sprague Dawley rats were Ovx or sham-operated (Sham) and kept sedentary for 8 weeks under a standard diet. Thereafter, rats were transferred for three weeks in running wheel cages for Tr or kept sedentary (Sed) with or without Ros treatment (5mg/kg/day). Six groups were formed: Sham-Sed treated with saline (Sal) or Ros (Sham-Sed-Sal; Sham-Sed-Ros), Ovx-Sed treated with Sal or Ros (Ovx-Sed-Sal; Ovx-Sed-Ros), Ovx trained treated with Sal or Ros (Ovx-Tr-Sal; Ovx-Tr-Ros). Ovx-Sed-Sal rats depicted higher (P < 0.05) body weight, plasma total cholesterol (TC) and LDL-C, and liver TC content compared to Sham-Sed-Sal rats. In contrast, mRNA levels of liver PCSK9, LDLR, LRP-1 as well as plasma PCSK9 concentrations and protein levels of LRP-1 were reduced (P < 0.01) in Ovx-Sed-Sal compared to Sham-Sed-Sal rats. However, protein levels of LDLR increased (P < 0.05) in Ovx-Sed-Sal compared to Sham-Sed-Sal rats. Treatment of Ovx rats with Ros increased (P < 0.05) mRNA and protein levels of LRP-1 and PCSK9 but not mRNA levels of LDLR, while its protein abundance was reduced at the level of Sham rats. As a result, plasma LDL-C was not reduced. Exercise alone did not affect the expression of any of these markers in Ovx rats. Overall, Ros treatment corrected Ovx-induced decrease in gene expression of markers of cholesterol metabolism in liver of Ovx rats, but without reducing plasma LDL-C concentrations. Increased plasma PCSK9 levels could be responsible for the reduction of liver LDLR protein abundance and the absence of reduction of plasma LDL-C after Ros treatment.
本研究的目的是调查单独使用瑞舒伐他汀（Ros）治疗三周以及联合自愿训练（Tr）对八周龄去卵巢（Ovx）大鼠肝脏中参与胆固醇代谢的基因（低密度脂蛋白受体（LDLR）、前蛋白转化酶枯草溶菌素9（PCSK9）、低密度脂蛋白受体相关蛋白1（LRP-1）、固醇调节元件结合蛋白2（SREBP-2）、诱导降解物1（IDOL）、酰基辅酶A胆固醇酰基转移酶2（ACAT-2）和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR））表达的影响。将Sprague Dawley大鼠进行去卵巢手术或假手术（Sham），并在标准饮食条件下久坐8周。此后，将大鼠转移至跑步轮笼中进行三周的训练（Tr），或在有或无Ros治疗（5mg/kg/天）的情况下久坐（Sed）。形成了六组：用生理盐水（Sal）或Ros治疗的假手术-久坐组（假手术-久坐-Sal；假手术-久坐-Ros）、用Sal或Ros治疗的去卵巢-久坐组（去卵巢-久坐-Sal；去卵巢-久坐-Ros）、用Sal或Ros治疗的去卵巢训练组（去卵巢-Tr-Sal；去卵巢-Tr-Ros）。与假手术-久坐-Sal大鼠相比，去卵巢-久坐-Sal大鼠的体重、血浆总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）以及肝脏TC含量更高（P<0.05）。相比之下，与假手术-久坐-Sal大鼠相比，去卵巢-久坐-Sal大鼠肝脏中PCSK9、LDLR、LRP-1的mRNA水平以及血浆PCSK9浓度和LRP-1蛋白水平降低（P<0.01）。然而，与假手术-久坐-Sal大鼠相比，去卵巢-久坐-Sal大鼠LDLR的蛋白水平升高（P<0.05）。用Ros治疗去卵巢大鼠可增加（P<
