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目的探讨姜黄素联合胡椒碱在预防高脂饮食小鼠胆囊胆固醇结石形成中的作用。方法 50只C57BL6小鼠全部喂给高脂饮食,同时每天灌喂500或1 000 mg/kg姜黄素,每天加或不加20 mg/kg胡椒碱,共4周。统计胆囊结石成石率,收集血液、胆汁、胆囊、肝脏以及小肠,测量胆囊容积,称量肝脏质量,检测血液及胆汁生化指标,对小鼠肝脏及胆囊进行HE染色,同时对胆囊行天狼猩红染色,real-time PCR、Western blot方法检测小鼠小肠Neimann-Pick C1-like 1(NPC1L1)及固醇调控元件结合蛋白-2(SREBP2)表达。结果与单纯高脂饮食喂给相比,姜黄素联合应用胡椒碱可降低70%高脂饮食所致的小鼠胆囊胆固醇性结石的形成,同时降低胆固醇〔(2.89±0.14)mmol/L比(6.86±0.16)mmol/L,P<0.05〕及甘油三酯〔(0.84±0.09)mmol/L比(1.59±0.10)mmol/L,P<0.05〕,还可降低小鼠小肠组织中NPC1L1 m RNA(0.46±0.023比1.00±0.014,P<0.05)及蛋白表达(0.47±0.01比1.00,P<0.05),同样降低小鼠小肠组织中SREBP2 m RNA(0.80±0.028比1.00±0.061,P<0.05)及蛋白表达(0.77±0.05比1.00,P<0.05)。结论姜黄素能够预防高脂饮食小鼠胆囊胆固醇性结石的形成,NPC1L1及SREBP2可能参与了这个过程,胡椒碱可以增加姜黄素的生物利用度,增强其作用。
Objective To investigate the effect of curcumin combined with piperine on the prevention of cholesterol gallstone formation in gallbladder in mice fed high-fat diet. Methods Fifty C57BL6 mice were all fed a high-fat diet while 500 or 1000 mg / kg of curcumin were infused daily with or without piperine 20 mg / kg for 4 weeks. Gallstones were counted as stone, blood, bile, gallbladder, liver and small intestine were collected, volume of gallbladder was measured, liver mass was measured, biochemical indexes of blood and bile were tested, HE staining was performed on liver and gallbladder of mice, The expression of Neimann-Pick C1-like 1 (NPC1L1) and sterol regulatory element-binding protein-2 (SREBP2) in the small intestine of mice was detected by flow cytometry. Results Compared with simple hypercholesterolemic diet, curcumin combined with piperine could reduce the formation of gallstone gallstone in mice induced by 70% high fat diet and lower the cholesterol (2.89 ± 0.14 mmol / L ratio 6.86 ± 0.16) mmol / L (P <0.05) and triglyceride (0.84 ± 0.09 mmol / L) (1.59 ± 0.10 mmol / L, P <0.05) RNA (0.46 ± 0.023 vs 1.00 ± 0.014, P <0.05) and protein expression (0.47 ± 0.01 vs 1.00, P <0.05) also reduced the small intestine SREBP2 mRNA (0.80 ± 0.028 vs 1.00 ± 0.061, P < 0.05) and protein expression (0.77 ± 0.05 vs 1.00, P <0.05). Conclusion Curcumin can prevent gallstone gallstone formation in mice fed high-fat diet. NPC1L1 and SREBP2 may be involved in this process. Piperine can increase the bioavailability of curcumin and enhance its effect.