The Study Of The Impact Of Simvastatin And With Ezetimibe Schemes On The Liver And Kidney Function On Rats Sclerosis Model

Objective: The purpose of this research is to further validate the impactsto the level of the lipid and the arguments of their changes. At the sametime, it aims to observe the influence to the livers (including ALT, ASTand their macroscopic observation and the HE staining of them), thekidneys(including Scr, BUN, UA, U-pro, Ucr, Ccr and their macroscopicobservation and the HE staining of them) when using small doses ofsimvastatin combined with ezetimibe, large dose of simvastatin only andsmall dose of simvastatin only to treat the hyperlipidemia rats.Method: We divided42health6weeks male Wistar rats into five groupsrandomly: normal control group(A), high lipid model group(B),Simvastatin (10mg·kg-1·d-1) treatment group(C), Simvastatin (20mg·kg-1·d-1) treatment group(D) and Simvastatin (10mg·kg-1·d-1) withEzetimibe(5mg·kg-1·d-1) treatment group(E). Group A was given commondiet, groups B to E were given high fat diet. Then8weeks later, two ofthem were executed to get aorta to observe whether we had make themodel successfully. The rest40rats were aparted into different metaboliccages to collect their urine in24h (They were given enough water and no food). Then we collected their blood through vena ophthalmica, whatwere preserved in the fridge of minus80degree Centigrade. From thenon, the rats of NO.3to NO.5were given corresponding doses ofsimvastatin and ezetimibe by intragastric administration. Totally4weeks.Then, we collected the blood of femoral artery. After that, wedeterminated the level of TG, TC, LDL-C, HDL-C, ALT, AST, Scr, BUN,UA, U-pro, Ucr, CCr, CRP, IL-4, IFN-γ. Then we executed all of them toget the aortic, hepatic tissues and renal tissues. We fixed them and stainedthem with HE staining and computed renal index.Result: Eight weeks later,compared with the control group, there wereseveral changes in the high lipid groups below.(1)Lipid: In the aspect of TG, it increased statistically in every high lipidgroups compared to the control group and the same to TC and LDL-C.Tothe level of HDL-C, it decreased statistically.(2)Hepatic functions: The levels of ALT and AST increased statistically inthe high lipid groups compared with the control group, which was ademonstration that high lipid food are harmful to the liver.(3)Renal functions and CRP: In the aspect of Ccr, it decreasedstatistically in every high lipid groups compared to the control group.While in the aspect of BUN,it increased statistically and the same to UA, U-pro, CRP. That was a demonstration that high lipid food are harmful tothe kidney.After using drugs four weeks later,there were several changescompared with each other.(1)Lipid: The TG, TC, LDL-C levels of the drug treatment groupsdecreased statistically compared to the high lipid model group, and itwas more and more obvious from group C to E.While to the level ofHDL-C, compared with group C and D, it increased statistically in groupE,which showd that the three drug treatments can significantly decreasethe serum lipid level. Among all these treatments, the combined treatmentgroup was the most obvious.(2)Hepatic functions: The levels of ALT and AST decreased significantlyin the combined treatment group. The single simvastatin groups weren’tbe increased or deseased significantly. It showd that the combinedtreatment group has a good impact on the liver. While wheather or notsimvastatin can do harm to the liver were not be confirmed.(3) Renal functions and CRP: In the aspect of Ccr, it increasedstatistically in drug treatment groups compared to the high lipid controlgroup, of which the large dose of simvastatin group was the most obvious.While in the aspects of BUN, UA, U-pro and the kidney index, it decreased statistically in group C to E compared to group B, of which thelevel of U-pro changed the most.(4)The aortic, liver and kidney pathology: The aortic tunica intima in Agroup was smooth, and the tunica intima of artery intima endothelial cellsarranged in neat rows. There were obvious plaque and lipid core in theaortic tunica intima in group B. The aortic intimal plaque Group C to Edecreased and the lipid core was significantly reduced,the most obviousgroup was E. The liver structure was normal in group A, and the liver cellvolume were not increasing or decreasing, mutually aligned. The livercells in group B were observed obviously fatty degeneration,in which theliver cells arranged in disorder and the liver cell volume increased. Itimproved a lot in Group C to E,especially in group E.The glomerularstructure in group A was clear, normal, with renal corpuscle in order.Glomerular volume increased in group B with mesangial cellproliferation. It improved a lot in Group C to E, especially in group D.Conclusions:1.Small doses of simvastatin with ezetimibe can better reduce the level ofTC, TG, LDL-C compared to single large dose or small dose ofsimvastatin. Also the level of HDL-C can be improved better. It can notonly decrease the level of lipid but also protect the liver function. 2. Each treatment group can protect the kidney function. We can find thatthe level of BUN, UA, U-pro, CRP and kidney index are decreased andCcr is improved. Large doses of simvastatin can better protect the Ccrlevel and decreased the level of U-pro compared to another two treatmentgroups. At the same time, it can better promote the morphous of renalglomerulus.