食品科学

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根皮苷通过下调小肠NPC1L1和HMG-CoA还原酶表达降低血液胆固醇水平

申婷婷,刘素稳,赵 江,汪名春,常志勇,王 浩   

  1. 1.天津科技大学生物工程学院,天津 300457;2.河北科技师范学院食品科技学院,河北 秦皇岛 066604;
    3.天津科技大学食品工程与生物技术学院,天津 300457;4.安徽农业大学食品科学与工程系,安徽 合肥 230036
  • 出版日期:2014-09-15 发布日期:2014-09-12

Phlorizin Decreases Serum Cholesterol by Downregulating Intestinal NPC1L1 and HMG-CoA Reductase

SHEN Ting-ting, LIU Su-wen, ZHAO Jiang, WANG Ming-chun, CHANG Zhi-yong, WANG Hao   

  1. 1. College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China;
    2. College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066604, China;
    3. College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China;
    4. Department of Food Science and Engineering, Anhui Agricultural University, Hefei 230036, China
  • Online:2014-09-15 Published:2014-09-12

摘要:

以高脂高胆固醇膳食喂饲仓鼠为动物模型,研究根皮苷对仓鼠血脂水平及小肠胆固醇代谢相关基因的调控影响。36 只实验动物随机分成对照组和3 个不同剂量根皮苷干预组(3、6、9 g/kg),测定血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)及高密度脂蛋白胆固醇(high density lipoproteincholesterol,HDL-C)水平,气相色谱法检测肝脏中胆固醇含量及粪便固醇排泄量,实时定量荧光聚合酶链式反应(real-time polymerase chain reaction,Real-Time PCR)分析小肠胆固醇合成、吸收、转化及排泄基因的表达水平。血脂测定结果显示,血清TC、TG水平随给予根皮苷添加量增加而降低,且高剂量组具有显著性(P<0.05或P<0.01);6、9 g/kg根皮苷剂量组,血清中HDL-C水平极显著升高(P<0.01)。气相色谱检测结果显示,根皮苷剂量组仓鼠肝脏中胆固醇含量较对照组随根皮苷剂量增加而降低,且6、9 g/kg组具有极显著差异(P<0.01);粪便中总中性固醇排泄量与根皮苷给予量正相关,且都具有显著性差异(P<0.05或P<0.01),总酸性固醇排泄量根皮苷剂量组相比对照组增加,且6 g/kg组显著增加(P<0.05),9 g/kg组极显著增加(P<0.01)。Real-Time PCR检测结果显示,根皮苷剂量组小肠中胆固醇合成限速酶HMG-CoA还原酶、小肠胆固醇吸收关键蛋白NPC1L1、胆固醇酯化酶ACAT2、微粒体转运蛋白MTP的mRNA表达水平较对照组显著降低(P<0.05或P<0.01);给予根皮苷后,肠道中促进胆固醇向外排泄基因ABCG5/8表达水平显著升高(P<0.05或P<0.01)。因此,根皮苷对高脂高胆固醇膳食饲喂仓鼠胆固醇代谢平衡的调节可能是通过对小肠胆固醇吸收、转化等基因表达的抑制,上调胆固醇排泄基因的表达实现的。

关键词: 根皮苷, 仓鼠, 小肠, 血脂, 基因表达

Abstract:

Destroying the balance of plasma cholesterol into hypercholesterolemia is a major risk factor for atherosclerosis.
The aim of this report was to investigate the effects of phlorizin on blood cholesterol level and gene expression of cholesterolregulating
enzymes in Golden Syrian hamsters maintained on a 0.1% cholesterol high fat diet. Totally 36 hamsters were
randomly divided into control group and three experimental groups with 3, 6, and 9 g/kg phlorizin, and serum total
cholesterol (TC), triacylglycerols (TG) and high-density-lipoprotein-cholesterol (HDL-C) were detected. Then, the contents
of cholesterol in liver and fecal neutral and acidic sterols were determined by GC. The gene expression of cholesterolregulating
proteins in the small intestine was assayed with Real-Time PCR. Serum TC and TG were significantly decreased
in 9 g/kg phlorizin group compared with those in the control group, while HDL-C in 6 and 9 g/kg phlorizin groups were
significantly increased (P < 0.01). The hepatic cholesterol level in the experimental groups supplemented with 6 and 9 g/kg
phlorizin was significantly lower than that in the control group (P < 0.01). Higher excretion of fecal cholesterol was observed
in the phlorizin groups. The amount of total fecal neutral sterols was increased compared with that in the control group
(P < 0.05 or P < 0.01). The excretion of total fecal acidic sterols was increased as the amount of phlorizin increased (6 g/kg,
P < 0.05; 9 g/kg, P < 0.01). It was also found that the cholesterol-lowering activity of phlorizin was associated with downregulation
of intestinal 3-hydroxy-3-methyl glutaryl-CoA (HMG-CoA) reductase, niemann-pick C1-like 1 (NPC1L1), acyl-
CoA-cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and up-regulation of ATPbinding
cassette transporter such as subfamily G member 5 and 8 (ABCG5/8) transporters. The mechanisms underlying the
cholesterol-lowering activity of phlorizin were mediated most likely by increasing the sterol excretion and decreasing the
cholesterol absorption and synthesis.

Key words: phlorizin, hamsters, small intestine, serum lipid, gene expression

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