[Atorvastatin inhibits cardiomyocyte apoptosis via down-cegulation the expression mitofusin 2 after myocardial ischemia/reperfusion injury in rats].
OBJECTIVE
To investigate the effects of atorvastatin (statin for short) on cell apoptosis and the expression of mitofusin 2 (Mfn2) after myocardial ischemia/reperfusion (I/R) injury in rats.


METHODS
A total of 32 male Sprague-Dawley rats were randomly divided into sham group, I/R group, statin group 1 and group 2, with 8 rats in each group. The rats in the two statin groups were given atorvastatin 10 and 40 mg/(kg.d) daily since the 7th day before I/R injury, respectively. The rats in the I/R group were given distilled water instead. The I/R injury models were induced by the ligation of left anterior descending (LAD) artery for 30 minutes followed by recovering the blood stream. Three hours after reperfusion, the I/R injured areas of rat hearts were harvested, and cardiomyocyte apoptosis was assessed by in situ terminal deoxynucleotidyl transferase (TdT)-dUTP nick-end labeling (TUNEL). Immunohistochemistry and Western blotting were respectively performed to determine the expressions of Mfn2 and phosphorylated Akt (p-Akt).


RESULTS
Three hours after reperfusion, the cardiomyocyte apoptosis and Mfn2 protein expression of the I/R and statin treatment groups remarkably increased, and p-Akt expression significantly decreased (P<0.01) as compared with those of the sham group. Compared with those of the I/R group, cardiomyocyte apoptosis and Mfn2 protein expression of statin groups were significantly reduced in a slightly dose-dependent manner (P<0.05), and p-Akt expression was obviously raised (P<0.05).


CONCLUSIONS
Atorvastatin can suppress cardiomyocyte apoptosis after I/R injury in rats, which may be related to the down-regulated expression of Mfn2.
Department of Cardiology, Wuhan Central Hospital, Wuhan 430014, China.
Wei
W
Zhou
Ling
L
Chen
Manhua
M
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D015536:Down-Regulation / Q000187:drug effects*; D020558:GTP Phosphohydrolases; D006538:Heptanoic Acids / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006538:Heptanoic Acids; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010750:Phosphoproteins; D011758:Pyrroles; D000069059:Atorvastatin; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat