| Objectives:As constant improvement of people's living standard and ageing of population, coronary artery disease,especially attack rate of acute myocardial infarction(AMI) is on the rise. In surgery, the method for early treatment of AMI is acute coronary artery bypass graft(ACABG). It inevitably accompanied by ischemical reperfusion injury after ACABG. The role of matrix metalloproteinase-9(MMP-9) in the ischemical reperfusion injury process is one hot spot of medical research in recent years. Matrix metalloproteinases-9 with molecular weight also named gelatinase-B is max the enzyme in the matrix metalloproteinase family. It can degrade extracellular matrix(ECM). Interleukin-8 (IL-8) produced by many cells is an early inflammatory cytokine which had a role of chemotaxis, 6～10KD protein . IL-8 has a role of chemotaxis in neutrophilic granulocyte, and conduct neutrophilic granulocyte degenerating and particulate releasing.It is an important regulatory factor in the active and migratory process of neutrophilic granulocyte and an important transmitter in entering damage tissue. It is also the cell factor which has an important role in the process of damage pathology. IL-8 can induce infiltration and activation of neutrophilic granulocyte to cardiac muscle cell, and also promote the occurrence of ischemical reperfusion injury after ACABG. MMP-9 and IL-8 probably engage in much physiopathologic process after myocardial infarction. This empirical studied the change of MMP-9 and IL-8 in blood plasma level, researched their time process after reperfusion of big rabbits with AMI, analyzed the relationship between MMP-9 and IL-8 and AMI′s severity, analyzed its possible physiopathologic mechanism in ischemical reperfusion, and explored their clinical meaning and correlation.Methods: Fifty-seven New Zealand white rabbits, 3～4 months old, 2500g～3000g in weight,were randomly divided into sham operation group(n=7), myocardial infarction group(n=15)and ischemic reperfusion group(n=35). Ischemic reperfusion group were randomly divied into 2h group(n=10),4h group(n=12)and 6h group(n=13). All big white rabbits were anesthetized through intraperitoneal injection with 10% Chloral Hydrate with dose of 3ml/kg before operation. And we opened their chest from 2nd to 4th rib interval along left edge of sternal bone. Heparin sodium were injected with dose of 1mg/kg after opening chest to prevent from thrombosis after blocking coronary artery. Electrocardiogram was used to monitor during the period of making models. The electrocardiogram of sham operation group had no change . The S-T segment ofⅡ,Ⅲ,aVF lead rasied in myocardial infarction group and ischemic reperfusion group. In sham operation group suture line was put under posterior descending coronary artery, but wasn't deligated. In myocardial infarction group posterior descending coronary artery was permanently deligated. In ischemic reperfusion group posterior descending coronary artery was tied, and then was loosed after 2h, 4h and 6h, making the model of ischemic reperfusion. Antibiotics were injected to prevent from infection after operation. Mid point of the posterior descending coronary artery were equally deligated or blocked in every group. Five big white rabbits were preoperatively taken to draw blood in order to measure the level of MMP-9,IL-8 and CM-MB as normal level. The blood in all groups was drew off 2ml through jugular vein in 12h, 1d, 2d, 3d, 5d and 7d, and centrifuged 10 minutes by 3000 roll/minute after anticoagulating of heparin. Supernatant was extracted and preserved in refrigerator of below 80℃to save for pre-emergency. ELISA was used to measure content of MMP-9 and IL-8 in blood plasma. Full automaticity biochemistry instrument was used to measure content of CK-MB. Perfusate was made with ABS and acetone at the proportion of 1:20. Rabbits were injected perfusate to moulde from the hole of right coronary artery after they were sacrificed. And then put rabbits'hearts into hydrochloric acid of 37% to dissolve and observed condition of revascularization. One-factor analysis of variance and relative analysis were carried out with statistics software of SPSS 13.0. LSD-t test was used to compare between each group. Pearson test was taken to analyze their correlation. P<0.05 means statistical significance.Results:(1)Survival condition of big rabbits: 0 died in sham opration group. 5 rabbits died in myocardial infarction group. The mortality was 33.33%. 0, 2, 4 rabbits died respectively in ischemic reperfusion 2h group, 4h group and 6h group. The rate of death was respectively 0, 16.67% and 30.77%. The survivals were taken as research objects.(2)Change condition of MMP-9: MMP-9 gradually began to rise after 12h in myocardial infarction group and ischemic reperfusion group, reached peak in third day, and then gradually declined, but still higher than normal level in seventh day. The longer time of ischemia(ischemic reperfusion 2h group, 4h group and 6h group and myocardial infarction group), the higher level of MMP-9 was. MMP-9 in myocardial infarction group and ischemic reperfusion group were dramatically higher than sham group's. There was statistical significance(P<0.05); MMP-9 in myocardial infarction group was obviously higher than ischemic reperfusion group's, and there was statistical significance(P<0.05); MMP-9 in ischemic reperfusion 6h group were significantly higher than ischemic reperfusion 4h and 2h group's. There was a significant difference(P<0.05); MMP-9 in ischemic reperfusion 4h group was obviously higher than ischemic reperfusion 2h group(P<0.05). If MMP-9 in sham operation group compared with normal level, there was no statistical significance(P>0.05).(3)Change condition of IL-8: IL-8 gradually began to rise after 12h in myocardial infarction group and ischemic reperfusion group, reached peak in second day, and then gradually declined, but recovered normal level in fifth day. The longer time of ischemia(ischemic reperfusion 2h group, 4h group and 6h group and myocardial infarction group), the higher level of IL-8 was. IL-8 in myocardial infarction group and ischemic reperfusion group were dramatically higher than sham group's at 12h, 1d, 2d and 3d. There was statistical significance(P<0.05); IL-8 in myocardial infarction group was obviously higher than ischemic reperfusion group's, and there was statistical significance ( P<0.05 ) ; IL-8 in ischemic reperfusion 6h group were significantly higher than ischemic reperfusion 4h and 2h group's. There was a significant difference(P<0.05); IL-8 in ischemic reperfusion 4h group was obviously higher than ischemic reperfusion 2h group(P<0.05). If IL-8 in sham operation group compared with normal level, there was no statistical significance(P>0.05). (4) Correlation of MMP-9 and IL-8: Blood plasma MMP-9 level were closely correlated with blood plasma IL-8 level in ischemia reperfusion groups during 3 days, but not correlated in the fifth and seventh day.Conclusions:(1)Blood plasma MMP-9 and IL-8 were closely correlated with ischemia time of AMI. The longer ischemia time, the higher blood plasma level of MMP-9 and IL-8 was. Blood plasma level of MMP-9 and IL-8 can pretest severity of acute myocardial infarction. The higher blood plasma level, the more serious AMI was. (2) The earlier revascularization, the lower MMP-9 and IL-8 was; while the lower MMP-9 and IL-8, the lower mortality was. It can be inferred that the impossible benefit of revascularization after acute myocardial infarction was correlated with lowering blood plasma level of MMP-9 and IL-8.(3)Blood plasma MMP-9 level were closely correlated with blood plasma IL-8 level in ischemia reperfusion group during 3 days. Blood plasma IL-8 could raise blood plasma MMP-9 level in the process of ischemic reperfusion.(4)If compared to normal level, the MMP-9 and IL-8 level in sham operation group had no obvious difference. It explained that operation had no influence on level of MMP-9 and IL-8. |
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