| ObjectiveIn this experiment,rats with hyperlipidemia as a carrier,coptis Fructus Evodiae 1:1(berberine evodiamine compatibility)for the study,study coptis Fructus Evodiae simba open bitter drop compatibility lip id-lowering effect,with Leptin-AMPK signaling pathway lowering its target for the study of mechanisms of action,reveal coptis Fructus Evodiae simba open bitter drop compatibility scientific connotation.MethodIn this study,108 male SD rats were randomly selected 12 as the control group during the modeling,the rest are in the model group.Eating high-fat diet in a free way to build and hyper lip idemic rats,recording in general(hair,activity,stool,mental state)and food consumption in rats during the modeling day,every three days record weight changes.Weekly randomly selected six rats(control group 3,model 3)tail vein blood serum cholesterol(TC),triglyceride(TG)levels to evaluate the success of modeling.The first six weeks of modeling,a random sample of serum TC level model group than the control group significantly increased about 2 times the control group,suggesting that successful model.After the modeling,in addition to the control group,all rats were randomly divided into eight groups lipid levels,namely,positive group(simvastatin)(10mg/kg),berberine high dose group(72.8mg/kg)berberine low dose group(36.4mg/kg),evodiamine high dose group(16.8mg/kg),evodiamine low dose group(8.4mg/kg),compatibility of the high dose group(89.1 mg/kg),compatibility low dose group(44.5mg/kg),a total of nine groups of eight.The dosing volume 1 ml/100g.During the administration period,in addition to the control group eating normal food,the rest are eating high-fat diet.During the administration period,recorded in general(hair,activity,stool,mental state)and food consumption in rats every day,every three days record weight changes.Continuous administration of 60 days,the day before the end of the experiment,water fasted for 16 hours and the abdominal aortic blood serum was separated,blbod lipid levels(cholesterol,triglycerides,HDL,LDL)and serum thin Su(Leptin)content.Isolated rat liver surgery photographs record its shape and weighed to calculate the liver index,Elisa kits to detect liver TC,TG,liver histopathology testing.Western blot method to detect liver adenosine monophosphate-activated protein kinase(AMPK),acetyl coenzyme A carboxylase(ACC)protein expression,carnitine palmitoyl transferase-1(CPT1),PCR method to detect liver AMPK,ACC,CPT1 gene expression.Statistics and analysis of experimental data.Results1.Establishment and evaluation of experimental rat model of hyperlipidemia Control rats generally in good condition;abnormal signs did not appear,and no death.Model rats reduced food intake,individual rat fur stands chlorosis,dull;loose stool,excrement more heavy odor;the spirit of excitement,increased activity.During the modeling,the body weight of rats in the model group was significantly lower than the control group(P<0.01).Modeling sixth week,serum TC level model group was significantly higher than the control group(P<0.01),about 2 times the control group,suggesting that successful model.2.The compatibility of coptidis and Fructus Evodiae effect on body weight levels Body weight of rats in the model group than the control group reduced(P<0.05).Administration of the first 12 days,24 days,60 days,and other multiple-dose group,high dose group compatibility body weight increased significantly(P<0.01),higher than its weight alone berberine,Evodia base.Weight and low-dose groups,no significant increase in the trend.3.The compatibility of coptidis and Fructus Evodiae effect on blood lipid levels After 60 days of administration,compatibility and high dose group was significantly lower serum TC effect(P<0.01),serum TC level be low berberine and high dose group,high dose group evodiamine.Each treatment group serum TG no improvement.Serum HDL value in the model group lower than control group,but not statistically significant.And other multiple-dose group,evodiamine high and low dose group,serum HDL levels higher than wait for the next multiple dose berberine,compatibility group.Each administration group on serum LDL hyperlipidemia rats were downregulated,and the significant effect(P<0.01).Compatibility of high and low dose group and other multiple doses below the levels of LDL alone berberine,Evodia base.4.The compatibility of coptidis and Fructus Evodiae effect on the liver index,hepatic TC,TG and hepatic pathologyLiver index was significantly higher in model group than the control group(P<0.01),the control group was about 2-fold.Each dose group could improve the liver index(P<0.01).And other multiple-dose group,high compatibility,low-dose group were better than in the liver and other multiple-dose group was treated with berberine,Evodia base.Model group rat liver TC,TG was significantly higher than the control group(P<0.01).Evodiamine high and low dose group liver TC,TG levels lower than wait for the next multiple dose berberine and compatibility group.Control group of normal hepatocytes or very mild steatosis.Model of liver cells and severe steatosis.The number of lipid droplets in the cytoplasm and the number and size compared with the model group,liver tissue of rats ofeach administration group was mild or moderate liver cells steatosis,fatty degeneration of cells,but have different degrees of reduction.Wherein evodiamine high-dose group,high dose group berberine,compatibility high dose group more significant improvement(P<0.01)on the severity of hepatic steatosis.5.The compatibility of coptidis and Fructus Evodiae of lipid-lowering effect on protein expression of Leptin-AMPK signaling pathwaySerum Leptin model group than the control group significantly decreased nearly eight-fold(P<0.01);after 60 days of administration,the serum Leptin rats were increased.And other multiple-dose group,high dose group berberine Leptin levels above evodiamine high-dose group,high dose group compatibility;compatibility level higher than the low dose group Leptin berberine,evodiamine low dose group.Model group AMPK-P protein expression than the control group reduced(P<0.05);administered for 60 days,compatibility and low dose group AMPK-P protein expression was upre gulated most significant(P<0.01),other groups liver AMPK-P protein expression in model group were raised with respect to the role,but not statistically significant.And other multiple-dose group,high compatiility,low dose group AMPK-P protein expression was higher than that with berberine,Evodia base.ACC-P expression in the model group than the control group reduced(P<0.05);after 60 days of administration,compatibility and low dose group,high dose group of berberine ACC-P expression increased effect(P<0.05),the rest of the group ACC-P expression relative to the model group were downregulated,but not statistically significant.And other multiple-dose group,low dose group compatibility expression of ACC-P alone is higher than berberine,Evodia base.High-dose groups was not statistically significant.60 days after the administration,rats CPT1 protein expression group was lower than the control group(P<0.05).A significant increase in the low-dose group compatibility CPTI expression compared with model group(P<0.01),than wait for the next multiple dose alone berberine,Evodia base.High dose groups increased CPT1 not significant.6.The compatibility of coptidis and Fructus Evodiae of lipid-lowering effect on Gene expression of Leptin-AMPK signaling pathwayAMPK gene expression in model group compared with the control group reduced,blank control group AMPK gene expression model group 2 times;after 60 days of administration,compatibility and low dose group gene expression regulated AMPK most significant,approximately 2.5 times the model group.In addition to Evodia low dose group,and the remaining AMPK in liver gene expression in each group were raised with respect to the role of the model group.And other multiple-dose group,low dose group compatibility AMPK gene expression higher than that with berberine,Evodia base.ACC gene expression in model group than the control group decreased control groupACC gene expression model group 1.5 times;60 days a:fter the administration,in addition to the compatibility of the high dose group,the other groups of gene expression were increased role of ACC.And other multiple-dose group,low dose group ACC-compatibility gene expression higher than that with berberine,Evodia base.60 days after the administration,rats CPT1 protein expression group was lower than the control group,blank control group CPTI gene expression model group 1.4 times;a significant increase in the low-dose group compatibility CPT1 expression compared with model group,the model group was about 1.4 times,better wait for the next multiple dose alone berberine,Evodia base.High dose groups increased CPT1 gene expression was not significant.ConclusionThe compatibility of coptidis and Fructus Evodiae in improving hyper lip idemic rats body weight,lowered serum TC,LDL levels,reduce liver indices having asynergistic effect.The compatibility of coptidis and Fructus Evodiae regulat protein and gene expression of each target of Leptin-AMPK signaling pathway also having a synergistic effect.The compatibility of coptidis and Fructus Evodiae blongs to Simba open bitter drop,this project is to reveal its scientific connotation. |
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