[The effect of protease-activated receptor2 on rat apoptotic cardiomyocytes underwent ischemia reperfusion injury].
OBJECTIVE
To investigate the effect of protease-activated receptor 2 (PAR-2) on rat apoptotic cardiomyocytes underwent ischemia reperfusion (I/R) injury.


METHODS
Healthy male Sprague-Dawley rats were randomly divided into five groups (n = 8 each): sham-operation group, I/R (ligating the left coronary artery for 30 minutes and followed by 120 minutes reperfusion) group and three SLIGRL-NH2 groups treated with intravenous PAR-2 agonist SLIGRL-NH2 at different doses (0.5, 1, 3 mg/kg) 5 minutes before reperfusion. Apoptic cardiomyocytes was detected by TUNEL staining and by DNA ladder on agarose gel electrophoresis. Bax and Bcl-2 expression in myocardium was analyzed by immunohistochemical technique. The mRNA expression of PAR-2 was determined by Real-time quantitative polymerase chain reaction (RT-PCR).


RESULTS
(1) The apoptosis index and the expression of Bcl-2 and Bax were significantly increased in IR group and SLIGRL-NH2 groups than those in sham group (P < 0.05-0.01). (2) Compared with I/R group, the apoptosis index and the expression of Bax were significantly reduced while the expression of Bcl-2 and PAR-2 mRNA were significantly upregulated by SLIGRL-NH2 in a dose-dependent manner. (3) DNA Agarose gel electrophoresis demonstrated that DNA ladder existed in I/R and 0.5 mg/kg SLIGRL-NH2 group, but not in 1, 3 mg/kg SLIGRL-NH2 groups.


CONCLUSIONS
PAR-2 agonist SLIGRL-NH2 could reduce myocardial apoptosis by upregulating the Bcl-2 and PAR-2 mRNA level and downregulating Bax expression in a dose-dependent manner in this rat I/R model.
Department of Cardiology, First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, China.
Xiao-Hong
XH
Tong
Jia-Wang
JW
Ding
Jun
J
Yang
Chao-Qi
CQ
Liu
Yan
Y
Zhang
Song
S
Li
Wen-Hui
WH
Li
Li
L
Li
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D044464:Receptor, PAR-2; D051028:bcl-2-Associated X Protein