title: Reduced apoptosis after acute myocardial infarction by simvastatin.
abstract: To observe the effect of simvastatin in patients with acute myocardial infarction in rabbits against myocardial apoptosis, and to explore its possible mechanism. Male New Zealand white rabbits were randomized into three groups, including the myocardial infarction group (12 rabbits), the simvastatin treatment group (15 rabbits), and the sham group (12 rabbits). In the simvastatin treatment and myocardial infarction groups, the rabbits received myocardial infarction surgeries. While in the sham group, loose knots were tied in the left anterior descending coronary artery branches. The simvastatin treatment group was given simvastatin by oral gavage 24 h after surgery. Parameters, which included left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, and left ventricular mass index, were recorded in these three groups. Edge myocardial infarction and myocardial cell apoptosis were analyzed using TUNEL assay, and Bcl-2, Bax, and Caspase-3 protein levels were detected by Western blot. Acute myocardial infarction model was successfully established in rabbits by ligation of the left anterior descending coronary artery. Compared with the myocardial infarction group, left ventricular end-diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly reduced and left ventricular ejection fraction (LVEF) increased in the simvastatin treatment group. Compared with the sham group, LVEDD and LVESD were significantly increased and LVEF decreased in the simvastatin treatment group. All the differences were statistically significant (P < 0.05). Left ventricular mass index in the simvastatin treatment group was statistically lower than the myocardial infarction group. Compared with the sham group, left ventricular mass index in both the simvastatin treatment and myocardial infarction groups was significantly increased. The differences of the above comparisons were statistically significant (P < 0.05). Compared with the sham group, the apoptosis rate of the myocardial infarction group and the simvastatin treatment groups was significantly increased as shown by TUNEL assay, however, the apoptosis rate of the simvastatin treatment group was significantly lower than that of the myocardial infarction group. All the differences among above comparisons were statistically significant (P < 0.05). Bcl-2 levels significantly increased in the simvastatin treatment group compared with the myocardial infarction group, but Bcl-2 levels in both groups were significantly lower than the sham group. However, Bax protein levels showed inverse expression with Bcl-2. Meanwhile, Caspase-3 protein expression showed similar trend with Bcl-2. Simvastatin can improve cardiac function after myocardial infarction and reduce apoptosis of myocardial cells, possibly by decreasing Bax and Caspase-3 expression and increasing the expression level of Bcl-2.
authors.affiliation: Emergency Department, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen Univeristy, Guangzhou, 510210, Guangdong, China, drkeqinluo@163.com.
authors.forename: Ke-qin
authors.initials: KQ
authors.lastname: Luo
authors.forename: Hui-bao
authors.initials: HB
authors.lastname: Long
authors.forename: Bing-can
authors.initials: BC
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019821:Simvastatin; D053148:Caspase 3