[Protective effects of 11,12-epoxyeicosatrienoic acid preconditioning and postconditioning on myocardial ischemia/reperfusion injury in rats].
To explore the effects of 11,12-epoxyeicosatrienoic acid (11,12-EET) preconditioning and postconditioning on myocardial ischemia/reperfusion (IR) injury in rats, the IR injury model was built by stopping perfusion for 40 min followed by reperfusion for 30 min, and the changes of mitochondrial functions, myocardial metabolism and function were measured. Langendorff-perfused isolated rat hearts were divided into 4 groups: control group, persistently perfused with Krebs-Henseleit (K-H) fluid for 100 min; IR group, stopped perfusion for 40 min followed by reperfusion for 30 min; Pre-EET group, preconditioned with 6.24×10(-9) mol/L 11,12-EET for 5 min twice before subjected to ischemia; Post-EET group, postconditioned with 6.24×10(-9) mol/L 11,12-EET for 30 s twice before reperfusion. The computer-based electrophysiological recording system was used to measure the changes of maximal rate of the pressure increase in contract phase (+dp/dt(max)), maximal rate of the pressure decrease in diastole phase of heart (-dp/dt(max)), left ventricular end-diastolic pressure (LVEDP) and difference of left ventricular pressure (DLVP). The activities of lactate dehydrogenase (LDH) in effluent, Ca(2+)-ATPase, Na(+)-K(+)-ATPase and succinate dehydrogenase (SDH) in mitochondria were measured with colorimetry method; superoxide dismutase (SOD) activity was measured with hydroxylamine method and malondialdehyde (MDA) content in myocardial tissues was measured with TBA method. The results showed that: (1) Compared with that in the control group, the myocardial functions, the values of SOD, SDH and Na(+)-K(+)-ATPase were decreased in IR group (P<0.05); the values of LDH, MDA and Ca(2+)-ATPase were increased (P<0.05) in IR group. (2) Compared with that in IR group, the values of SDH and Na(+)-K(+)-ATPase were increased (P<0.05) and the value of Ca(2+)-ATPase was decreased (P<0.05) in both Pre-EET and Post-EET groups. But no significant differences were detected between Pre-EET and Post-EET groups. (3) Compared with IR treatment, both 11,12-EET preconditioning and postconditioning caused significant decreases in MDA content and leakage of LDH, amendment of heart functions and increases in SOD activity (P<0.05). But there were no significant differences between 11,12-EET preconditioning and postconditioning. These results indicate that 11,12-EET preconditioning and postconditioning can protect myocardium from IR injury by improving mitochondrial functions, up-regulating the activities of Na(+)-K(+)-ATPase and SDH, and down-regulating the activity of Ca(2+)-ATPase in mitochondria. Moreover, 11,12-EET preconditioning and postconditioning also elevate the activity of SOD and reduce the content of MDA, suggesting that 11,12-EET can depress the oxidative stress in IR rat heart.
Wang
Yan-Xia
YX
Department of Pathophysiology, Capital University of Medical Sciences, Beijing 100069, China.
Lu
Ling-Qiao
LQ
Wang
Xiao-Yan
XY
Mu
Jing
J
Zeng
Xiang-Jun
XJ
Zhang
Li-Ke
LK
Tang
Chao-Shu
CS
Hao
Gang
G
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D057775:Ischemic Postconditioning; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D018384:Oxidative Stress; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D015126:8,11,14-Eicosatrienoic Acid