The effect of PSD-95 inhibitor ZL006 on hypoxic-ischemic brain damage in neonatal rats / 中国小儿急救医学

ABSTRACT

Objective:To explore the effect of PSD-95 inhibitor ZL006 in neonatal rats with hypoxic-ischemic brain damage(HIBD) and its potential mechanism.Methods:The seven-day-old healthy Wistar rats( n=80) were randomly divided into control group( n=20), sham operation group( n=20) and operation group (HIBD model group, n=40). The operation group was randomly divided into ZL006, treatment group (intraperitoneal injection of ZL006, 10 mg/kg, n=20) and non-treatment group ( n=20). The neonatal rats of each group were randomly selected on the 1st and 7th day after operation, and the degree of cerebral infarction was observed by triphenyl tetrazolium chloride staining.The protein expression level of brain tissue in the injured area was examed by Western blot, and the effects of ZL006 on oxidative stress and antioxidant enzymes in rats with HIBD were evaluated by ELISA. Results:(1) On the first day after operation, the brain injury was the most serious in the non-treatment group, and the cerebral infarction decreased in the ZL006 treatment group.On the 7th day after operation, a little infarction could be seen in the operation group, but there was no significant difference among other three groups.(2)On the first day after operation, the expression of PSD-95 protein in the operation group was significantly higher than that in the control group and sham operation group( P<0.01). There was significant difference in the expression of PSD-95 protein between the ZL006 treatment group and the non-treatment group ( P<0.05). On the 7th day after operation, there was no significant difference in the expression of PSD-95 protein among three groups.(3)On the first day after operation, the expression of 4-hydroxynonenal in the operation group was significantly higher than that in the control group and sham operation group( P<0.01), and that in the non-treatment group was higher than that in the ZL006 treatment group ( P<0.05). On the 7th day after operation, there was no significant difference in the expression of 4-hydroxynonenal among three groups.(4) On the first day after operation, the expression of superoxide dismutase in the operation group was significantly lower than that in the control group and sham operation group( P<0.01), and that in the non-treatment group was lower than that in the ZL006 treatment group ( P<0.05). There was no significant difference in the expression level of superoxide dismutase among three groups on the 7th day after operation. Conclusion:It is suggested that PSD-95 may be involved in the early pathogenesis of HIBD, and ZL006 may have neuroprotective effect on HIBD in newborn rats.