Efficacy And Safety Of Combination Therapy With Atorvastation And Fenofibrate In Rats With Combined Hyperlipidemia

Objective:The aim of this study was to evaluate the efficacy and safty of combination therapy with Atorvastatin and Fenofibrate in rats with combined hyperlipidemia.On the base ofachiving the better results,the side effects did not occur,for example myopathy,rhabdomyolysis and so on.By doing the trial,we tried to provide some evidence for clinical physicans to treat patients with combined hyperlipidemia.Methods:84 Wistar rats were randomized into group N,group C,group A, group AJ,group AF,group CAF and group CAFH.The other groups were fed with fatty food for eight weeks except group N fed with common food.At the end of the fourth week,group A,group AJ,group AF,group CAF and group CAFH were administrated drugs,group A(Atorvastatin 1.8mg/kg),groupAJ(Atorvastatin 0.9mg/kg+Gemfibrozil 54mg/kg,respectively at night and in the morning),group AF(Atorvastatin 0.9mg/kg+Fenofibrate 18mg/kg,respectively at night and in the morning),group CAF(Atorvastatin 0.9mg/kg+ Fenofibrate 9mg/kg,together) and group CAFH(Atorvastatin 0.9mg/kg+ Fenofibrate 18mg/kg,together).After 8 weeks,the blood was taken out and all rats were killed.Take out of the liver and calculate the hepatic index.TC,TG,LDL-C,HDL-C,ALT, AST,Cre,BUN,Mb,CK and hs-CRP were measured at the end of the fourth,the sixth and the eighth week.The HE pathologic slices of livers were observed and calculate inflammatory scores.Results 1.At the end of the fourth week,the levels of TC,LDL-C,HDL-C,TG, LP(a)in group N were sigficantly lower than the other groups(P＜0.01).At the end of the eighth week,compared with group C,the levels of TC,LDL-C,TG,LP(a) decreased in the goups administrated drugs,however the effects in group CAF were inferior to group A,group AJ,group AF and group CAFH.The levels of HDL increased in all combination therapy groups,especially in group AJ,group AF and group CAFH.2.At the end of fouth week,the groups with fatty food achieved much more weight than group N.At the end of sixth and eighth week,the weight in group C was still bigger than the other groups.3.At the end of fouth week,the levels of hs-CRP in group N were lower than the others.At the end of sixth and eighth week,the levels of hs-CRP could be better controlled in the groups administrated drugs especially in group AJ,group AF and group CAFH. 4.At the end of sixth and eighth week,the levels of K~+ were higher than the other groups.5.At the end of fourth week,the levels of Cre,BUN were higher in all the groups with fatty food.At the end of eighth week,the levels of Cre,BUN were lower in the groups administrated drugs.However,there were no difference among all the groups administrated drugs.6.At the end of fourth week,the levels of ALT,AST were higher in the groups with fatty food.At the end of eighth week, the levels of ALT,AST in group C were higher than the other groups.The levels of ALT,AST were relatively higer in the group CAF and group CAFH than group A, group AJ and group AF.7.At the end of sixth and eighth week,the levels of Mb in group CAFH were the highest among all the groups.8.At the end of the fourth week,there were no difference among the levels of CK in every group. At the end of sixth and eighth week,the levels of CK in group AJ,group CAF,groupCAFH were higher than other groups,especially group CAFH.9.The liver index in groups administrated drugs decreased dramatically,especially in group A,group AJ,group AF and group CAFH.10.The liver fatty degeneration occurred in all the groups with fatty food.But the group C was the most serious, the group AJ,group AF and group CAFH were better,11.The inflammatory scores were the most high in group C.Those in the group AF,group AJ and group CAFH were the lowest. Conclusion:1.Combination therapy of atorvastatin plus fenofibrate or gemfibrozil can strengthen the effects on adjusting lipids and controlling the level of hs-CRP.So combination therapy can keep TC,LDL-C,HDL-C and TG in the appropriate range and restrain the inflammatory reaction.The effects of combination therapy are stronger than double doses of atorvastatin.2.The effects of atorvastatin 0.9mg/kg plus fenofibrate 18mg/kg are equal to atorvastatin 0.9mg/kg plus gemfibrozil 54mg/kg.3.Hyperlipodimia can induce the damage of liver function.However administrating drugs separately can ruduce the hepatic damage and protect the liver function.Fenofibrate plus atorvastatin are better than atorvastatin plus gemfibrozil.The hepatic negative effects of combination therapy are also related to the doses of drugs.4.Hyperlipodimia can induce the damage of renal function.Atorvastatin plus fenofibrate or gemfibrozil can protect the renal function in combined hyperlipedimia.So combiantion therapy is relatively safe to the renal function.5.Administrating atorvastatin plus fenofibrate separately have relatively less effect on the level of CK and the negative effects were related to the doses of drugs.The level of CK is more sensitve than Mb with the response to myopathy.6.Atorvastatin plus fenofibrate or gemfibrozil can decrease the effects of hepatic fatty degeneration,inflammation and necrosis.