[Protective effects of hypoxia-inducible factor-1 alpha on myocardial ischemia/reperfusion injury in rat and the role of protein kinase C in signal pathway].
OBJECTIVE
To study the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in a rat model of myocardial ischemia/reperfusion injury (IRI) and the role of protein kinase C (PKC) in signal pathway.


METHODS
A rat model of myocardial IRI was reproduced by 30 minutes of left anterior descending coronary artery (LCA) occlusion followed by 180 minutes of reperfusion. Thirty-two healthy male Wistar rats were randomly divided into four groups. The first group was ischemic preconditioning (IPC) group; the second group was simple IRI group; the third group was IPC plus PKC inhibitor group (IPC+I group); the fourth group was the sham-operation group without ligation of LCA. Eight rats were used in each group. The heart was harvested 180 minutes post-reperfusion, the mRNA and protein expression of HIF-1 alpha and heme oxygenase-1 (HO-1) were assessed. Meanwhile, the protein expression of caspase-3 was assayed. Blood samples were obtained from heart to determine the levels of interleukin-8 (IL-8) and myeloperoxidase (MPO).


RESULTS
The mRNA and protein expression of HIF-1 alpha and HO-1 increased significantly in the IRI group compared with the sham-operation group, while the protein expression of caspase-3 increased significantly in the IRI group (HIF-1 alpha mRNA: 0.849+/-0.032 vs. 0.356+/-0.022, HIF-1 alpha protein: 0.762+/-0.042 vs. 0.324+/-0.016, HO-1 mRNA: 0.862+/-0.045 vs. 0.332+/-0.012, HO-1 protein: 0.792+/-0.044 vs. 0.335+/-0.031, caspase-3 protein: 0.371+/-0.015 vs. 0.061+/-0.012, respectively, all P<0.01). The levels of IL-8 and MPO increased significantly in the IRI group [IL-8: (812+/-26) ng/L vs. (72+/-13) ng/L, MPO: (78.7+/-2.9) kU/L vs. (13.3+/-1.5) kU/L, both P<0.01]. The protein and mRNA expression of HIF-1 alpha and HO-1 increased significantly in the IPC group compared with IRI group (HIF-1 alpha mRNA: 1.412+/-0.039, HIF-1 alpha protein: 1.362+/-0.045, HO-1 mRNA: 1.523+/-0.038, HO-1 protein: 1.420+/-0.041, respectively), meanwhile the protein expression of caspase-3 (0.129+/-0.019) decreased significantly in the IPC group (all P<0.01). The levels of IL-8 [(432+/-59) ng/L] and MPO [(43.2+/-5.9) kU/L] decreased significantly in the IPC group compared with IRI group (both P<0.01). All above parameters showed no significant change between IPC+I group and IRI group.


CONCLUSIONS
HIF-1 alpha plays a protective role in myocardial IRI, PKC is an important signal pathway of HIF-1 alpha gene expression in IRI.
Niu
Tie-sheng
TS
Department of Cardiology, the Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China. syniuts@yahoo.com.cn
Qi
Guo-xian
GX
Fu
Peng
P
Sun
Ying-xian
YX
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009195:Peroxidase / Q000097:blood; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D009195:Peroxidase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D011493:Protein Kinase C; C505410:Casp3 protein, rat; D053148:Caspase 3