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Mechanism Of Simvastatin On Reversing Ventricular Remodeling In Rats After Myocardial Infarction

Posted on:2005-04-14Degree:MasterType:Thesis
Country:ChinaCandidate:D Y ZhangFull Text:PDF
GTID:2144360122990124Subject:Internal Medicine
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Background and Objective : Recent studies in vitro have demonstrated that hydroxymethylglutaryl coenzyme A reductase inhibitors (Statins) could attenuate the signals transduction induced by angiotensin II (Ang II) and other neuroendocrine factors independent of cholesterol availability. Because angiotensin II is involved in left ventricular (LV) remodeling after myocardial infarction (MI), it has been hypothesized that statins may exert beneficial effects on the ventricular remodeling after MI. So the aims of this study were to assess the in vivo effects of Simvastatin (Sim) on cardiac remodeling in rats with an experimental MI and explore its mechanism.Methods: MI was maded in Wistar rats by 1'gation of the left anterior descending coronary artery. Rats with extensive MI were randomized to treat with placebo or Sim (20mg/kg per day or 40mg/kg per day) as via gavage for 8 weeks starting on the 3th postoperative day. There were four groups: Sham group( n=8 ), MI group( n=8 ), 20mg Sim group( n=9 ) and 40mg Sim group( n=8 ). Infarct size, cholesterol levels,hemodynamics, total and regional ventricular weights, hydroproline content (HC) and collagen volume fraction (CVF) of type I and III of four groups were recorded after 8 weeks. The gene expressions of a -myosin heavy chain ( a -MHC), 0 - myosin heavy chain ( 0 -MHC), collagen type I and III were detected by RT-PCR. The expression of skeletal a -actin (Sk a -Actin) was detected by immunohistochemistry.Results: (1)Infarct size and cholesterol levels were similar among all groups. (2) Placebo-treated infarcted rats (MI group) developed significant increase in left /right ventricular weight index, compared with Sham group (P<0.01), while in Sim-treated rats, a significant reduction of left /right ventricular weight index was founded (P<0.01 versus MI group). (3) LV end-diastolic pressure (LVEDP) was increased in MI rats on placebo (P<0.01 versus Sham group), and it was significantly reduced by Sim treatment (P<0.05 versus MI group). LV systolic pressure (LVSP) was decreased in MI group (P<0.01 versus Sham group), while it was significantly increased by Sim treatment (P<0.05 versus MI group). (4)In non-infarcted zone CVF of type I and type III and their ratio in MI group were higher than Sham group (P<0.01), CVF of type I and type III and their ratio in both Sim groups decreased significantly.(5)The mRNA expression of a -MHC was down-regulated in MI group (P<0.01 versus Sham group), and it was significantly up-regulated in both Sim groups (P<0.01 versus MI group). The mRNAexpressions of 0-MRC, collagen type I and III were up-regulated in MI group compared with Sham group (P<0.01), while Sim-treatment significantly down-regulated their expression (P<0.01 versus MI group). ㏕he level of Sk a -Actin in MI group increased and in Sim groups attenuated.Conclusion: That Statins induced the regression of hypertrophy gene expression and fibrosis may be responsible for the amelioration of ventricular remodeling and cardiac function by Simvastatin.
Keywords/Search Tags:Simvastatin, cardiac remodeling, cardiac hypertrophy, fibrosis
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