木豆叶总芪对高脂模型兔的降脂作用及调节机制

Hypocholesterolemic effect of total stilbene from Cajanus cajan L. in hyperlipidemic rabbit model and regulatory mechanism

目的研究木豆叶总芪(TSC)对高脂模型兔脂质代谢的影响及可能的分子机制。方法将36只雄性新西兰兔分为对照,模型,TSC高、中、低剂量和血脂康6组,于0、2和6周末测血脂,6周末测肝脏脂质并行病理学检测;将THP-1细胞诱导成巨噬细胞,用[3H]胆固醇预处理48 h后分为对照、木豆叶总芪单体成分C03高、中、低剂量和雌二醇5组,作用24 h后加入apoAI作用12 h,检测各组上清液和细胞内[3H]胆固醇含量,计算细胞胆固醇流出率,Western blot检测各组细胞ABCA1表达。结果与模型组相比,TSC高剂量使兔血清和肝脏TC分别下降35.36%和35.97%(P<0.01),TG分别下降12.34%(P<0.05)和41.32%(P<0.01),血清LDL-C下降29.07%(P<0.01);HE染色:TSC高剂量组肝脂肪病变明显轻于模型组。C03高、中剂量作用后细胞胆固醇外流率分别提高55.39%和24.97%(P<0.01)。C03高剂量使ABCA1蛋白表达显著增加。结论 TSC能抑制高脂饮食所致高脂血症,其降脂作用可能与上调细胞ABCA1表达,进而促进胆固醇逆转运有关。

Objective To investigate the potential hypolipidemic effects of total stilbene from Cajanus cajan L.（TSC） in rabbits fed with a high-lipid diet and the mechanism of regulation of cholesterol metabolism.MethodsThirty-six male rabbits were divided into six groups： control group,high lipid model group,TSC-treated with 200,100,50 mg/kg,and Xuezhikang treated group.The effects of TSC were investigated by monitoring serum and liver lipid profile in rabbits.THP-1 cells were induced to macrophages by PMA.The macrophages were labeled with cholesterol.These cells were divided into five groups,i.e,normal group,Cajanin high concentration group（CH）,Cajanin mean concentration group（CM）,Cajanin low concentration group（CL） and estradiol（E2） group.The cells were cultured for 24 hours in the serum-free RPMI 1640 medium containing 2mg/ml bovine serum albumin（BSA） in the presence or absence of Cajanin（30 μmol/L,3 μmol/L,0.3 μmol/L） or 17β-estradiol（1 μmol/L）.The macrophages were washed with PBS again and incubated in the serum-free RPMI 1640 mediumcontaining apoA-I（10 μg/mL） for 12 hours.The radioactivity of samples of both supernatants and cell lysates were determined using the liquid scintillation counter（Beckman,LS 6000SC,USA）.Fractional cholesterol efflux was calculated,and the ABCA1 protein was quantified by Western blot.Results In TSC（200 mg/kg） group,the serum and hepatic TC were reduced by 35.36% and 35.97%（P0.01）;the TG contents of serum and liver were also lowered by 12.34%（P0.05） and 41.32%（P0.01）.At the same time,serum LDL-C decreased by 29.07%（P0.01）.The cholesterol efflux percentage from macrophage was increased by 55.39% and 24.97%（P0.01） respectively in CH and CM group.The expression of the ABCA1 was significantly increased in CH group.Conclusion TSC has potential hypolipidemic effects,possibly via up-regulating the ABCA1 protein expression,subsequently resulting in increased macrophage cholesterol efflux and RCT.