Metabolic changes of arachidonic acid after cerebral ischemia-reperfusion in diabetic rats.
The purpose of this study is to discuss an important component-arachidonic acid (AA) cascade of inflammatory reaction in diabetic rats with cerebral ischemia. Using the model of middle cerebral artery occlusion (MCAO), we have compared the expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and measured the levels of their products prostaglandin E2 (PGE(2)) and cysteine-containing leukotrienes (cys-LTs) after different reperfusion periods in diabetic and normal rats. Cerebral ischemia-reperfusion was accompanied by increased expression of COX-2 and release of PGE(2), peaking at 12 h after reperfusion. The expression of COX-2 was maintained at a high level until 24 h after reperfusion, while the levels of PGE(2) were declined rapidly to baseline. The expression of 5-LOX and levels of cys-LTs reached a peak at 6 and 12 h after reperfusion, respectively, and was returned to baseline at 24 h after reperfusion. Compared with normal rats, the expression of COX-2 and 5-LOX as well as release of PGE(2) and cys-LTs was elevated in the brains of diabetic rats, revealing a possible mechanism for hyperglycemia-mediated aggravation of cerebral ischemic injury. A reduction of arachidonic acid metabolites mediated by inhibitors of its metabolites could be helpful in preventing ischemic brain injury in diabetic rats.
Zhang
Ren-Liang
RL
Institute of Neurology, Fudan University, Shanghai, China.
Lu
Chuan-Zhen
CZ
Ren
Hui-Min
HM
Xiao
Bao-Guo
BG
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D051546:Cyclooxygenase 2; D003545:Cysteine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D015232:Dinoprostone / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007527:Isoenzymes / Q000096:biosynthesis; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D003545:Cysteine