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The Effects Of Combination Therapy Of Probucol And Atorvastatin On Adjusting Lipids And Inflammatory Factors In SHR Rats With High Lipids Diet

Posted on:2008-12-04Degree:MasterType:Thesis
Country:ChinaCandidate:G Y YiFull Text:PDF
GTID:2144360212987631Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: To evaluate the effects and hepatic security of combination therapy of larger doses of probucol and atorvastatin on adjusting lipids and inflammatory factors.Methods: 92 SHR rats were randomized into 5 groups: Group C (control group) was fed with normal diet and NS. Group M, Group A, Group P and Group A+P were all fed with high lipids diet. At the same time, group M was administrated NS, group P probucol (150mg/kg/day), Group A atorvastatin (10mg/kg/day), and Group A+P probucol (150mg/kg/day) plus atorvastatin (10mg/kg/day).After 8 weeks, all rats were killed. TC, TG, LDL, HDL, ALT, AST, IL-6, TNF-α and hs-CRP were measured respectively before and after experiment. At last liver pathological sections were observed on fatty degeneration and inflammation degree. Above indexes were compared intra-groups and inter-groups.Results: Serum TC, LDL, HDL levels in every group with high lipids diet were obviously higher than baseline data(P<0.01),but Serum TG levels decreased. Serum TC and LDL-C levels in group P, group A and group P+A were dramatically lower than group M (P<0.01) , especially in group P+A. Serum HDL-C levels in group P+A were obviously lower than group M and group A (P <0.01) ,but no significant deviation between group P+A and group P. Serum TG levels in group P+A and A were more lower than group M (P<0.01) ,group P+A were lower than group P, but no significant deviation between group P+A and group A. There was no difference between group P and group M. Serum IL-6, TNF-α and hs-CRP levels in group M obviously increased than ever and group C (P<0.01) , and in group P, group A, especially group P+A were lower thangroup M. Serum ALT and AST levels in every group with high lipids diet were higher than ever (P<0.01) and in group M were the highest. Serum ALT levels in group P+ A were higher than group P, but lower than group A. Serum AST levels in group P+A were obviously higher than group P (F<0.01) , but there was no difference between group P+A and group A. Every group with high lipids diet had fatty degeneration, but the degrees of fatty degeneration in group P+A were the lightest, and in group M were the severe group. The scores of inflammation degree in group P+A were lower than group M and group A, but no difference between group P and group P+A.Conclusion: 1. Combination therapy of probucol and atorvastatin can strengthen the effects on adjusting lipids, furthermore the effects are stronger than that of monotherapy. 2. Combination therapy of probucol and atorvastatin can decrease the levels of inflammatory factors, and the effects are better than monotherapy. 3. The hepatic negative effects of combination therapy are related to the doses of probucol and atorvastatin. 4. Decreasing the doses of probucol and atorvastatin can reduce hepatic damage during combination therapy.
Keywords/Search Tags:probucol, atorvastatin, spontaneously hypertensive rat, hyperlipemia, inflammation, fatty liver
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