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Effects Of Combination Atorvastatin And Soybean Isoflavones On Hypercholesterolemia And Lipoprotein Metabolism In Rats

Posted on:2007-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:X D HeFull Text:PDF
GTID:2144360182995956Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
HMG-CoA inhibitors were used to treat kinds of hyperlipidmia. Many great clinical testments all demenstreated that tatins can decrease the risk of blood vessel event. Many mauals also recommended the tatins as the answer of blood vessel event. Although, there is still almost 66.7% of patients that can not avoid the risk of blood vessel event. The circumstance makes researchers turn to the new minds of therapy methods. In this background, combination therapy are becoming the choice of doctors.Our study tryed the testment of the combination atorvastatin and soybean on the treatment of hyperlidmia. We found that the effects of combination on hyperlipidmia are superior than using atorvastatin alone as well as no more toxicity of liver and musle was found. On the basis of effects on hyperlipidmia ,we explore the relative mechanismPart â…  Selecting the optimum ratio of the combination by orthogonaldesign on hyperlipidmia rats model1.1 Selecting the optimum content of the combination atorvastatin, ginkgo flavonoids and pantethine.The results by orthogonal design method evince that atorvastatin 20mg/kg, ginkgo flavonoids 120mg/kg has the best effects on hyperlipidmia, pantethine is not the necessary factor. So the optimum ratio of the combination is atorvastatin: ginkgo flavonoids=1 :6.1.2 Selecting the optimum content of the combination atorvastatin, soybean isoflavones and pantethine.The results by orthogonal design method evince that atorvastatin 20mg/kg, ginkgo flavonoids 60mg/kg has the best effects on hyperlipidmia, pantethine is not the necessary factor. So the optimum ratio of the combination is atorvastatin: soybean isoflavones=1:3.1.3 Comparison of the two combination on the effects of treating hyperlipidmia1.3.1 Both ginkgo flavonoids and bean isoflavones can decrease TC, TG, LDL obviously;ginkgo flavonoids has no use on HDL on the controy of soybean isoflavones. 1.3.2 Comparison of the two combination toxicity on the liver and musleBoth ginkgo flavonoids and bean isoflavones have the similar effect on ALT -. AST, but ginkgo flavonoids affect CK greatly than bean isoflavones. 1.4 ConclusionsThe combination is atorvatatin and soybean isoflavones and the optimun ratio is 1:3.Part n Effects of the combination atorvastatin and soybean isoflavoneson hyperlipidmia of rats and rabbits2.1 The effects of combination on hyperlipid ratsThe combination were given to rats for twelve weeks and the results are: comparing to normal group, model TC> TG> LDL increased obviously (PO.05) , HDL decreased obviously (PO.05);comparing to model, high dose and middle dose group(the combination)can decrease TC> TG^ LDL obviously (PO.05), can increase HDL obviously(P<0.05);comparing to atorvastain, high dose and middle dose group can decrease TC, TG, LDL obviously (PO.05) , can increase HDL obviously (PO.05) . 2.1.2. The effects of combination on hyperlipid rabbitsThe combination were given to rats for twelve weeks and the results are: comparing to normal group, model TC, TG, LDL increased obviously (PO.05) , HDL decreased obviously (PO.05);comparing to model, high dose and middle dose group (the combination) can decrease TC, TG, LDL obviously (p<0.05), can increase HDL obviously (P<0.05);comparing to atorvastain, high dose and middle dose group can decrease TC, TG LDL obviously (p<0.05) , can increase HDL obviously(P<0.05 ) , low dose can ncrease HDL obviously.Part m Relative mechanism research of lipid regulation of combinationAT and SI on rats of hyperlipidmia3.1 Histom research on liver after using the combination AT+SIWe can see that normal liver were red and light;model were grey and oil-feeling;others were somehow lighter than model. Frozen sector staining said that normal hepatic cells were integrity and can not see any lipids in them;model cells exited lot of lipid;atorvastatin alone group lipid were less than model but more than high and middle group as well as similar with low dose group.3.2 Expression of mRNA of LDLR and apoA-1The results said that every group expression of LDLR and apoA-1 which was given medicine was higher than model;LDLR and apoA-1 expression of high and middle group were higher than atorvastatin alone (.P<0.05 );low dose group expression are similar with atorvastatin alone.3.3 Protein expression of LDLRWe can see by Western Blot experiment that normal and groups were given medicine protein expression were higher than model (p<0.05) , high and middle group expression were higher than atorvastatin alone (i>0.05 ) , low dose group expression was similar with atorvastatin.Part IV Conclusions4.1 The optimum content of the combination are atorvastatin and soybean isoflavones and the ratio of the combination is 1:3.4.2 The combination can decrease TQ TC, LDL comparing atorvastatin and increase HDL obviously.4.3 The mechanism of regulation on hyperlipidmia maybe increase the expression of LDLR mRNA and protein as well as the expression of apoA-1 mRNA.
Keywords/Search Tags:atorvastatin, soybean isoflavones, lipid, metabolism, low density lipid receptor
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