[The effect of pioglitazone on apoptotic cardiomyocytes for ischemia reperfusion].
OBJECTIVE
This study was to investigate the effect of pioglitazone on apoptotic cardiomyocytes with the model of ischemia-reperfusion at rat heart in vivo.


METHODS
Sprague-Dawley rats were randomly divided into two groups. One was 30 min reperfusion group, which was subdivided into sham (n = 5), model (vehicle, n = 6) and pioglitazone 3 mg/kg (n = 7) with 30 min ischemia followed by 30 min reperfusion to detect the area of myocardial infarction (MI). Another was 2 h reperfusion group, which was further subdivided into sham (n = 5), model (vehicle, n = 6), and pioglitazone 0.3 mg/kg (n = 6), 1 mg/kg (n = 7) and 3 mg/kg (n = 6). Apart from the sham, pioglitazone and vehicle were administered intravenously 30 min before occlusion. Then hearts were excised, paraffined and cut into 4 microm thick. Immunohistochemistry, in situ hybridization, TUNEL and DNA agarose gel electrophoresis were performed to detect the expression of Bax, Bcl-2, Caspase-3 and PPARgamma protein and PPARgamma mRNA.


RESULTS
(1) Compared with model, nec/aar of pioglitazone decreased by 28% (P < 0.01). The nec/lv ratio reduced by 32% (P < 0.01). (2) In a dose-dependent manner, the expressions of Bax and Caspase-3 were depressed, while the expression of Bcl-2, PPARgamma protein and PPARgamma mRNA were enhanced by pioglitazone. (3) The apoptotic index of subgroups injected pioglitazone reduced significantly by TUNEL compared with model (P < 0.05). Agarose gel electrophoresis demonstrated that DNA ladder existed in model, pioglitazone 0.3 mg/kg and pioglitazone 1 mg/kg, but not pioglitazone 3 mg/kg.


CONCLUSIONS
Pioglitazone could protect the heart from I/R injury evidenced by the improvement in the expression of PPARgamma at the levels of protein and mRNA after pioglitazone administrated, and by the decrease in the apoptotic cardiomyocytes.
Cao
Ze-ling
ZL
Department of Geriatric Cardiology, General Hospital of PLA, Beijing 100853, China.
Ye
Ping
P
Long
Chao-liang
CL
Chen
Kai
K
Li
Xiao-wei
XW
Wang
Hai
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology*
D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone