Study On The Effect And Mechanism Of Regulating Blood Lipid Of Microcospaniculata Flavonoids Dispersion Tablets

ObjectTo investigate therapeutic effect of Microcos paniculata flavonoids dispersion tablet(hereafter referred to as MPF tablet)on experimental hyperlipidemia and to explore the molecular mechanism,provide experimental basis for its drug development.Method1.The effect of MPF tablet on hyperlipidemia induced with Triton WR-1339 in miceNIH mice were randomly divided into 9 group as follow:normal group,model group,fenofibrate group,Xuezhikang group,ultra-high,high,middle,low and ultra-low doses of MPF tablet groups.10 mice for each group.All the drug groups were intragastric administered continuously for 7 days.All groups except normal group were injected into tail vein with WR-1339 Triton(300 mg/kg).1 h After the last administration,the serum TC and TG level were determined.2.The effect of MPF tablet on hyperlipidemia induced with yolk in miceNIH mice were randomly divided into normal group,model group,fenofibrate group,Xuezhikang group,high,middle,low doses of MPF tablet groups.10 mice for each group.All the drug groups intragastric administered continuously for 7 days.6 days after administration,all groups expect normal group were ip injection 75%yolk with 0.5 mL each mouse.1 h After the last administration,the serum TC level were determined.3.The effect of MPF tablet on hyperlipidemia induced with high fat emulsion in mice70 NIH mice were randomly divided into normal group,model group,fenofibrate group,Xuezhikang group,high,middle,low doses of MPF tablet groups.all groups expect normal group were intragastric administered high fat emulsion at morning,all the drug groups were administered at afternoon.7 days later,the serum TC and TG level were determined.4.The effect of MPF tablet on hyperlipidemia induced with high fat diet in rats70 SD rats were randomly divided into normal group,model group,fenofibrate group,Xuezhikang group,high,middle,low doses of MPF tablet groups.all groups expect normal group were fed with high fat diet for 8 weeks.4 weeks later,all the drug groups were administered.8 weeks later,the serum level of TC,TG,HDL-C,LDL-C,ApoAl and ApoB,and the activity of LPL and HL were measured.5.The effect of MPF tablet on hyperlipidemia induced with high fat emulsion in rats70 SD rats were randomly divided into normal group,model group,fenofibrate group,Xuezhikang group,high,middle,low doses of MPF tablet groups.All groups expect normal group were intragastric administered high fat emulsion 10 mL/kg at morning,each drug group was administered at afternoon.8 weeks later,APTT,PT in plasma and TC,TG in serum were determined.6.The effect of MPF tablet on hyperlipidemia induced with high fat diet in rabbits6 New Zealand rabbits were randomly selected as the normal group and fed with normal diet and the other 36 other were fed with high fat diet.2 weeks later,36 hyperlipidemia rabbits divided into model group,fenofibrate group,Xuezhikang group,high,middle,low doses of MPF tablet groups by TC level.Then each drug group was administered for 8 weeks.During the administration,the model group and the drug administration groups continued to fed with high fat diet every day.The level TC and TG in serum and liver tissue were measured,the expression of lipid metabolism related gene and protein were measured by real-time fluorescence quantitative PCR(RT-qPCR)method and Western blot method(Western blot).ResultsMPF tablets can significantly reduce the serum TC,TG level Of hyperlipidemia mice induced with Triton WR-1339 or emulsion high fat and reduced the serum TC level of hyperlipidemia mice induced with egg yolk.MPF tablet can significantly reduce serum concentration of TC,TG,LDL-C and ApoB and increase content of HDL-C and ApoAl,and enhance the activity of LPL,HL and general esterase of hyperlipidemia rats induced with high fat diet.It can lower TC,TG level and prolonged The plasma APTT time of hyperlipidemia rats induced with high fat emulsion.For hyperlipidemia rabbits induced by high fat diet,it also can lower the content of liver lipids and increase the genes and protein expression of ApoAl,LPL,CYP7A1 and LXR-a in the liver and inhibit the gene and protein expression of NPC1L1 in the ileum.ConclusionMPF tablet have effective blood lipid regulating effects by regulating the balance of ApoAl and increasing the activity of LPL and HL,general esterase in serum to accelerate the clearance of serum lipids.It can also reduce the lipid concentration in the liver tissue,preventing the formation of fatty liver,and regulate the function of blood coagulation in HLP.The related molecular mechanism may be described by follow:firstly,through the up-regulation of LXR-a and CYP7A1 expression,it promote the conversion of cholesterol to bile acids;secondly,through the up-regulation of ApoAl expression,it enhance cholesterol counter transport;thirdly,through the up-regulation of LPL expression,it promote the hydrolysis of triglycerides;finally,by inhibiting the expression of NPC1L1 ileum,inhibit cholesterol absorption and reabsorption.