[Effects of the alkaloid sinomenine on COX-2 activity and acute rejection in heart allografts: an experiment with rats].
OBJECTIVE
To evaluate the effects of the alkaloid sinomenine (SIN), a COX-2 inhibitor, on the acute rejection in heart allografts.


METHODS
Forty Wistar rats received the allograft of the hearts of 40 SD rats into the peritoneum. Then the recipients were randomly divided into 2 groups: SIN group, injected with SIN within 24 hours after the operation; and control group, injected with normal saline. The survival time was observed. The heartbeat was examined every day. The Wistar rats were killed 3 and 5 days after the operation respectively and the left ventricular tissues were taken to undergo pathological examination to detect the acute rejection and cell apoptosis. Immunochemistry and Western blotting were used to detect the COX-2 protein, and RT-RCR was used to detect the COX-2 mRNA. The mean numbers of apoptotic cardiomyocytes were determined with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) technique.


RESULTS
The survival time of the SIN group was 12.5 +/- 2.6 days, significantly longer than that of the control group (6.8 +/- 0.5 days, P = 0.001). Examination 3 and 5 days after the treatment of SIN, the extents of inflammatory reaction, endovasculites, myocardial edema, and cardiomyocyte damage in the allografts of the SIN group were all significantly less, the mean numbers of apoptotic cardiomyocyte was significantly smaller compared with the control group (all P < 0.05). At day 5, the levels of COX-2 protein and mRNA of the SIN group were both significantly lower than those of the control group.


CONCLUSIONS
Inhibition of COX-2 prolongs the allograft survival and reduces the myocardial damage and inflammation during acute cardiac allograft rejection.
Xu
Guang-quan
GQ
Department of Thoracic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Wang
Bin
B
Jin
Xiang-yuan
XY
Xia
Qiu-ming
QM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006084:Graft Rejection / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous
D009019:Morphinans; D012333:RNA, Messenger; C009271:sinomenine; D051546:Cyclooxygenase 2