Changes of cerebral matrix metalloproteinase-2 activity and oxidative glutathione level in newborn rats with persistent hypoglycemia

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LIU Jiang-qin(Department of Neonatology, shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Shanghai 200040, China)
CHEN Chao()
GUO Jia-lin(Department of Neonatology, shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Shanghai 200040, China)
YAO Ming-zhu(Department of Neonatology, shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Shanghai 200040, China)
LU Guo-qiang(Department of Neonatology, shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Shanghai 200040, China)
Journal Title:
Chinese Journal of Perinatal Medicine
Volume 15, Issue 01, 2012
Key Word:
Persistent hyperinsulinemia hypoglycemia of infancy;Matrix metalloproteinase-2;Glutathione;Glutathione disulfide;Rats

Abstract: Objective To investigate the effect of persistent hypoglycemia on the cerebral oxidative stress and matrix metalloproteinase-2 (MMP-2) activity of newborn rats and to explore the potential mechanism of hypoglycemia-induced brain injury of newborn. Methods Seven-day-old rats were injected insulin subcutaneously to induce persistent hypoglycemia.Cerebral cortex,hippocampus and thalamus were collected after 36 hours' observation and stored in -80 ℃.Glutathione (GSH)and glutathione disulfide (GSSG) were detected by commercial kit and GSSG/GSH was calculated.MMP-2 activity was detected by gelatin zymography. The data were analyzed by t test,one or two-wayanalysis of variance and Pearson correlation analysis.Six rats were set as the normal glucose group. Results Thirty-six hours after induction of hypoglycemia, the cerebral GSSG and GSSG/GSH of hypoglycemic pups elevated about 1.5 times higher than those of control group [GSSG:(15.89 ± 5.46) vs (6.15 ± 3.42) mg/g protein,t =3.704,P =0.004; GSSG/GSH:(5.58± 1.79) % vs (2.79±1.76) %,t =2.712,P=0.022].The GSSG and GSSG/GSH in thalamus of hypoglycemia were significantly higher than those of control [GSSG:(15.93 ± 5.75) mg/g protein vs (5.03±5.14)mg/g protein,P<0.05; GSSG/GSH:(6.50±3.25) % vs (2.41±3.12) %,P<0.05],whereas there were no significant differences in the cortex ard hippocampus.The total MMP-2 activity of hypoglycemic animals (2.22±0.59) was significantly higher than that of control (1.21± 0.17)(t=4.064,P=0.002),and significant differences were found between the two groups in cortex (2.14 ± 0.5 vs 1.17± 0.27),hippocampus (2.31± 0.72 vs 1.22 ± 0.37) and thalamus (2.22±0.68 vs 1.24±0.18) with all P<0.01].The activity of MMP-2 was positively related to GSSG (r=0.575,P=0.0002) and GSSG/GSH (r=0.484,P=0.0003). Conclusions Oxidative stress might play an important role in the persistent hypoglycemia induced brain injury of 7-day-old rat pups and thalamus might be most vulnerable to hypoglycemia.Hypoglycemia might also elevate MMP-2 activity which is positively related to GSSG level and GSSG/GSH of the brain.

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