The expression changes of MMP-9 and TIMP-1 in the brain of neonatal rats with hypoxic-ischemic brain damage(HIBD)

Objective To explore the mechanism of hypoxic-ischemic brain damage(HIBD) and provide new ideas for clinical treatment of hypoxic-iscbemic encephalopathy.Methods Neonatal 7-day-old Wistar rats were randomly divided into sham-operation control group,HIBD 6 h,12 h,24 h,48 h and 72 h groups(n =6 per group).The model of HIBD was induced by unilateral carotid ligation followed by timed exposure to 8% oxygen.The expression of MMP-9 mRNA and TIMP-1 mRNA in brain tissue of neonatal rats was measured by Real-time Q-PCR method.Results (1) The ligatod brainhemisphere of HIBD groups showed obvious edema from 12 h to 48 h after hypoxia -ischemia in the neonatal rats.(2) The expression of MMP-9 mRNA was very low in the sham-operation control group,but in HIBD groups,it began to increase at 6 h,and reached a peak at 24 h,then gradually decreased,but still maintained at high level at 72 h(P＜0.01).(3) The expression of TIMP-1 mRNA was aslo very low in the sham-operation control group.But in HIBD group,it increased slightly at 6 h,12 h and 24 h,compared to the sham-operation control group,each group was statistically significant(P＜0.05),with no significant difference among the three groups(P＞0.05),then decreased at 48 h and 72 h,but with no significant difference from sham-operation control group (P＞ 0.05).(4) The ratio of MMP-9 mRNA/TIMP-1 mRNA was normal in the sham-operation control group and HIBD 6 h group,it began to increase at 12 h,and reached a peak at 48 h,then gradually decreased,but still maintained at high level at 72 h(P ＜0.01).Conclusion Hypoxia-ischemia increases the expression of MMP-9 mRNA in brain tissue of nenatal rats,and the imbalance in the expression of MMP-9 mRNA and TIMP-1 mRNA possibly is one cause of brain edema induced by HIBD. Key words: Cerebral hypoxia; Cerebral ischemia; Neonatal rats; MMP-9; TIMP-1