Uridine 5'-triphosphate (UTP) protects against cerebral ischemia reperfusion injury in rats.
OBJECTIVE
To test the hypothesis that uridine 5'-triphosphate (UTP) had a protective effect on cerebral ischemia reperfusion (IR) injury in rats.


METHODS
Ischemia was induced by intraluminal suture of middle cerebral artery occlusion (MCAO). UTP solution was delivered through an indwelling tail venous catheter via microinfusion pump 30 min after the occlusion of MCA at a rate of 0.5 ml/100 g/min. Neurological deficit score (NDS) and brain water content were determined 24 h after reperfusion. Infarct volume was determined by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI), and nerve cell death was studied under an electron microscope.


RESULTS
There was a dose-dependent relationship among 10, 30 and 90 microg/kg UTP. The 90 microg/kg UTP had the best protective effect among the 3 groups. We compared 90 microg/kg UTP group with normal saline group and found that UTP had a protective effect on cerebral IR by the results of TTC staining (15.9% vs 30.5%, P<0.01). MRI at 6, 30 and 54 h after reperfusion showed smaller infarct volume in 90 microg/kg group compared with 0 microg/kg group (283.5, 352.1, 367.45 mm(3) vs 401.36, 576.75 and 677.11 mm(3), respectively), and electron microscope showed less nerve cell death in 90 microg/kg group compared with 0 microg/kg group.


CONCLUSIONS
UTP has a dose-dependent protective effect on cerebral IR.
Tian
Mou-Li
ML
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Zou
Zui
Z
Yuan
Hong-Bing
HB
Wang
Cheng-Cai
CC
Zhu
Qiu-Feng
QF
Xu
Hai-Tao
HT
Gao
Xin
X
Shi
Xue-Yin
XY
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013778:Tetrazolium Salts; D014544:Uridine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D014867:Water; C009591:triphenyltetrazolium; D014544:Uridine Triphosphate