姜黄素联合胡椒碱在预防小鼠胆囊胆固醇性结石中的作用

Effect of Curcumin Combined with Piperine on Preventing Cholesterol Gallstone in Mice

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 explore the role of curcumin combined with piperine on preventing cholesterol gallstone in C57BL6 mice. Methods All 50 C57BL6 mice were fed on lithogenic diet, with 500 or 1 000 mg/（kg·d） curcumin, with piperine 20 mg/（kg· d） or without piperine for 4 weeks. Formation rate of cholesterol gallstone was calculated, and blood, bile, gallbladder, liver as well as small intestine were collected. Furthermore, volume of gallbladder and weight of liver were measured as well as physiological and biochemical indexes of serum and bile were analyzed. Liver and gallbladder were observed by HE staining and （or） sirius red staining. Both Neimann-Pick Cl-like 1 （NPC1L1） and sterol regulatory element binding protein 2 （SREBP2） mRNA and protein levels were detected by real-time PCR and Western blot respectively. Results Compared with the mice fed on single lithogenic diet, the curcumin combined with piperine could decrease 70% formation of cholesterol gallstone in C57BL6 mice; at the same time, the curcumin combined with piperine could decrease both cholesterol level [ （2.89±0.14） mmol/L versus （6.86±0.16） mmol/L, P〈0.05 ]and triglyceride level （0.84±0.09） mmol/L versus （1.59±0.10） mmol/L, P〈0.05] in serum, and also decrease NPC1L1 mRNA （0.46±0.023 versus 1.00±0.014, P〈0.05） and protein expression （0.47±0.01 versus 1.00, P〈0.05） in the small intestine, and decrease SREBP2 mRNA （0.80±0.028 versus 1.00±0.061, P〈0.05） and protein expression （0.77±0.05 versus 1.00, P〈0.05）. Conclusion Curcumin combined with piperine could prevent the formation of cholesterol gallstone, NPC1L1 and SREBP2 might be participated in this progress, piperine might increase the bioavailability of curcumin and enhance its function.