摘要
目的研究丹皮酚对饮食诱导的高脂血症小鼠模型的脂代谢的影响及其机制。方法根据不同性质的饮食随机将雄性C57小鼠分为4组,每组10只:正常组、模型组、小大2个剂量实验组(250,500 mg·kg^(-1)丹皮酚),共干预12周。12周后,测定小鼠的体重、内脏脂肪率、血脂及脂代谢关键酶。以比色法检测小鼠的肝脂酶(HL)、脂蛋白脂酶(LPL)与HMG-Co A还原酶水平。以Real-time PCR检测固醇调节元件结合蛋白1c(SREBP-1c)、脂肪酸合酶(FAS)、乙酰辅酶A羧化酶α(ACCα)、羟甲基戊二酸单酰辅酶A还原酶(HMGCR)、硬脂酰辅酶A去饱和酶-1(SCD-1)的基因表达水平。结果经12周的高脂饮食,模型组的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)分别为(3.87±0.24),(0.87±0.10),(2.23±0.11)mmol·L^(-1),较正常组差异均有统计学意义(均P<0.05)。丹皮酚干预后,低高2个剂量实验组的TC、LDL-C、HDL-C分别为(3.13±0.22),(2.64±0.21)mmol·L^(-1);(0.62±0.08),(0.59±0.07)mmol·L^(-1);(1.92±0.09),(1.71±0.07)mmol·L^(-1)。与模型组比较差异均有统计学意义(P<0.05,P<0.01)。模型组的HL与LPL活性分别为(4.31±0.52),(8.49±1.11)U·m L^(-1),较正常组明显降低,差异均有统计学意义(均P<0.05)。在丹皮酚干预下,低高2个剂量实验组的HL与LPL活性分别为(6.92±1.01),(8.23±1.14)U·m L^(-1);(11.87±1.19),(15.42±1.75)U·m L^(-1),与模型组比较差异均有统计学意义(P<0.05,P<0.01)。高脂饮食诱导了HMG-Co A还原酶活性的增强,与正常组比较,模型组差异有统计学意义(P<0.01);但是这一增强作用被丹皮酚所抑制,与模型组比较差异均有统计学意义(P<0.05,P<0.01)。高脂饮食诱导SREBP-1c mRNA、FAS mRNA、ACCαmRNA、HMGCR mRNA及SCD-1 mRNA,模型组均较正常组分别上调了370%,420%,410%,400%,260%,差异均有统计学意义(均P<0.01)。低高2个剂量实验组降低了模型组的SREBP-1c mRNA、FAS mRNA表达,分别为27.7%,26.9%;57.4%,55.8%,差异均有统计学意义(均P<0.05)。结论丹皮酚能防治肥胖及高脂血脂,该作用可能与调节脂酶活性、抑制脂质合成相关。
Objective To explore the effect of paeonol on lipid metabolism of hyperlipidemia in mice and clarity the molecule mechanism.Methods According to diet,male C57 mice were randomly divided into normal group,model group,low and high dose experimental groups（paeonol 250,500 mg·kg-1）.Each group had ten mice.After 12 weeks,the body weight,visceral fat index,serum lipid and key enzymes were determined.The level of hepatic lipase（HL）,lipoprotein lipase（LPL）,HMG-CoA reductase enzyme（HMG-CoA RE） were determined by chromatometry.The mRNA expressions of lipid synthesis genes,such as sterol regulatory element-binding protein 1c（SREBP-1c）,fatty acid synthetase（FAS）,acetyl CoA carboxylase α（ACCα）,3-hydroxy-3-methylglutaryl-CoA reductase（HMGCR）,low-density lipoprotein receptor（LDLR）,stearoyl-CoA Desaturase-1（SCD-1） were analyzed by Real-time PCR.Results Feeding with high fat diet for 12 weeks,the total cholesterol（TC）,low density lipoprotein cholesterin（LDL-C）,high density lipoprotein cholesterin（HDL-C） in model group were（3.87 ± 0.24）,（0.87 ± 0.10）,（2.23 ± 0.11） mmol·L-1,respectively.Compared with normal group,the difference of the two factors had significantly（P 〈 0.05,P 〈 0.01）.The TC,LDL-C,HDL-C in experimental-L,experimental-H groups were（3.13 ± 0.22）,（2.64 ± 0.21） mmol · L-1;（0.62 ± 0.08）,（0.59 ± 0.07） mmol · L-1;（1.92 ± 0.09）,（1.71 ± 0.07） mmol·L-1,respectively.Compared with model group,the difference of the two factors in two experimental groups had significantly（P 〈 0.05,P 〈 0.01）.The level of HL and LPL in model group were（4.31 ± 0.52）,（8.49 ± 1.11） U · m L-1,respectively.Compared with normal group,the difference of the three factors had significantly（P 〈 0.05,P 〈 0.01）.The level of HL and LPL in experimental-L,experimental-H groups were（6.92 ± 1.01）,（8.23 ± 1.14） U·m L-1;（11.87 ± 1.19）,（15.42 ± 1.75） U·m L-1,respectively.Compared with model group,the difference of the two factors in two experimental groups had significantly（P 〈 0.05,P 〈 0.01）.In addition,paeonol can inhibit the activity of HMG-CoA reductase（HMGCR）.Compared with model group,the difference of the two factors in two experimental groups had significantly（P 〈 0.05,P 〈 0.01）.Compared with the normal group,induction of high fat diet of SREBP-1c mRNA、FAS mRNA、ACCα mRNA、HMGCR mRNA and SCD-1 mRNA,the model group was up-regulated 370%,420%,410%,400%,260% with significantly（all P 〈 0.01）.The experimental group reduced the expression of SREBP-1c mRNA,FAS mRNA,ACCα mRNA,HMGCR mRNA and SCD-1 mRNA in model group were 27.7%,26.9%; 57.4%,55.8% with significantly（all P 〈 0.05）.Conclusion Paeonol could prevent the obesity and hyperlipidemia,which might be related to the regulation of enzyme activity,the inhibition of lipid synthesis pathway.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2017年第22期2273-2277,共5页
The Chinese Journal of Clinical Pharmacology
关键词
丹皮酚
高脂血症
酶活性
脂质合成
氧化代谢
paeonol
hyslipidemia
enzyme activity
lipid synthesis
oxidative metabolism
