The Relationship Among Serum MMP-2, MMP-9, TIMP-1, VEGF And The Morphology Changes Of Cerebral Arteries In Cerebral Infarction Patients With Type 2 Diabetes Mellitus

OBJECTIVES:To utilize the magnetic resonance angiography(MRA) images, obtain the morphology of cerebral arteries in cerebral infarction patients with or without type 2 diabetes mellitus. To investigate the contrast differences of artery density and the interaction mechanisms of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9 (MMP-9),tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF) in blood vessel regeneration and collateral circulation formation.METHODS:(1) 120 patients were chosen in this experiment, including 60 cerebral infarction patients with type 2 diabetes mellitus (DMCI group), and 60 simple cerebral infarction patients (CI group). The two groups were assigned to 2 subgroups according to the diameter of cerebral infarction focus:the lacunar infarction patients group (d≦1.5cm) and the un-lacunar infarction patients group (1.5cm< d≦ 3cm).30 health check-up subjects act as control (C group).(2) To select standard foot-head posture pictures from MRA images. Each image was processed with Adobe Photoshop cs4 software, using relative density grid method to statistic the blood vessels density.(3) Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the levels of serum MMP-2, MMP-9, TIMP-land VEGF in DMCI group and CI group at 1 day and 7 days after the onset. (4) The SPSS 17.0 statistic software was used in analying the results by ANOVA,t tes,Pearson correlation analysis and multiple binary comparison between the sample mean differences.RESULTS:(1) The comparison results of the relative blood vessels density from standard foot-head position, anteroposterior position MRA pictures:The density in DMCI group was significantly lower than CI group (P<0.05), and the two groups were still lower than C group (P<0.05). To contrast all of the lacunar infarction patients:The density in DMCI group was significantly lower than CI group (P<0.05), and that two groups were still lower than C group (P<0.05) in foot-head position pictures. In anteroposterior position pictures, there were no differences among that three groups. To contrast all of the un-lacunar infarction patients:DMCI group had same density numerus as CI group (P>0.05), but DMCI and CI groups were significantly lower than C group (P<0.05). Both of the foot-head and anteroposterior position MRA pictures, in DMCI group, the squares of cerebral arteries correlated positively with diabetes mellitus pathogenesis (r=0.778, p=0.000; r=0.683, p=0.007)but negatively correlated with FBG and HbAlc (r=-0.802, p=0.000; r=-0.834, p=0.000. r= 0.731, p=0.010; r=-0.645, p=0.036). In the left lateral view, we can not find statistically significant differences.(2) The detection results of serum MMP-2 lecvel:At 1 day and 7 days after the onset of infarction, the level of serum MMP-2 was significantly higher in DMCI group compared with CI group and the normal control group (P<0.05). At 7 days they were significantly higher than that at 1 day in both DMCI group and CI group (P<0.05). To contrast all of the lacunar infarction patients:At 7 days the level of serum MMP-2 were significantly higher than that at 1 day in both DMCI group and CI group (P<0.05). Whaterer in all the un-lacunar infarction patients:there were no considerably differences between DMCI group and CI group at 1 day and 7 days (P> 0.05).(3) The detection results of serum MMP-9 and TIMP-1 lecvel:At 1 day and 7 days after the onset of infarction, the level of serum MMP-9 was significantly higher in DMCI group compared with C group (P<0.05). DMCI group had the same level as CI group at 1 day (P> 0.05). At 7 days they were significantly higher than that at 1 day in both DMCI group and CI group (P<0.05). To contrast all of the un-lacunar infarction patients:At 7 days the level of serum MMP-2 were significantly higher than that at 1 day in both DMCI group and CI group (P<0.05). While that were in all the lacunar infarction patients:there were no considerably differences between DMCI group and CI group at 1 day and 7 days (P>0.05).(4) The detection results of serum VEGF lecvel:DMCI group had a same serum VEGF lecvel as CI group (P>0.05) at the first day after onset, but a considerably higher one than C group (P<0.05). At the seventh day, that was significantly lower in DMCI group than CI group (P<0.05), but still higher than C group (P<0.05). The levels of serum VEGF at 7 days were significantly higher than that at 1 day in DMCI, CI groups and both of the lacunar, un-lacunar infarction patients groups(P<0.05).(5) The relationship results of MMP-2, MMP-9, TIMP-1, VEGF and some basal factors at 1 day:In DMCI group, the level of serum MMP-2, MMP-9 and TIMP-1 correlated positively with fasting blood-glucose (FBG) and HbAlc, but VEGF was negatively correlated with both of them. In CI group, the level of serum MMP-2, MMP-9, TIMP-1 and VEGF were not correlated with FBS, HbAlc, total cholesterol and triglyceride (P>0.05).CONCLUSIONS:There were significant disparation between the morphology of cerebral arteries in cerebral infarction patients with or without type 2 diabetes mellitus, and MMP-2, MMP-9, TIMP-1 and VEGF played important parts in the blood vessel regeneration, collateral circulation formation and the pathophysiologic processes of diabetic cerebral infarction.