The Effect Of FK506 On The Expression Of P-ERK And GAP-43 Protein In Neonatal Rats Hippocampus With Hypoxic-ischemic Brain Damage

Objectives: To investigate whether FK506 has neuroprotective effects againsthypoxic-ischemic brain damage in neonatal rats hippocampus and themechanism of it.Methods: 153 postnatal 7-day-old Sprague-Dawley rats were randomlydivided into three groups: sham-operation group (49), HIBD group(53) andintervention group (51). After the establishment of HIBD models, interventiongroup was injected FK506 at the dosage of 1mg/kg per day intraperitoneallyat 0h, 24h and 48h. The HIBD group was injected normal sodium at equalvolume at the same time. 1 pup in sham-operation group, 5 pups in HIBDgroup and 3 pups in intervention group died. The pups were perfused at 6h, 12h, 24h, 72h, 7d and 14d of recovery from hypoxia-ischemia(HI).Immunohistochemical technical was applied to investigate the expression ofp-ERK and GAP-43 in hippocampus of the brain, and physique developmentwas estimated at 72h, 7d and 14d. SPSS11.0 software was used to analyze thedata, a=0.05 was considered the level of significance. Results: 1. The pathological changes of right side of the brain was significantat 6-24h of HIBD and infarction of brain tissue had been observed by 72hgroup of HIBD. The changes were attenuated at 6-24h in intervention groupcompared with HIBD group. Infarction of brain tissue had not been observedin the intervention group.2.Weight of the rats was equal when entering the experiment(F=2.216,P=0.123). After HI, there were significant differences among the three groupsat 72h, 7d and 14d, which shown the highest in sham-operation group, and thelowest in HIBD group.3. p-ERK immunoreactive staining was weak in sham-operation group.The expression of p-ERK in HIBD group and intervention group increased at6h after hypoxia-ischemia, peaked at 24h, demonstrating significantdifferences at 6h, 12h, 24h and 72h (P＜0.05), but the degree of augmentationwas higher in intervention group than in control group, demonstratingsignificant differences at 6h, 12h, 24h and 72h (P＜0.05). From 6h to 7d, thelevel of GAP-43 in sham-operation group increased gradually and peakexpression was shown at 7d. Compared with sham-operation group, theexpression of GAP-43 in HIBD group and intervention group increased at 72hafter HI, and the peak time was shown at 7d, demonstrating significantdifference at 72h, 7d and 14d (P＜0.05). The degree of augmentation inintervention group was much higher that in control group, demonstratingsignificant differences at and 72h and 7d (P＜0.05). At 14d, the expression ofGAP-43 in intervention group decreased, demonstrating no significantdifference compared with HIBD group, but still differed statistically fromsham-operation group. Conclusions: 1. In hippocampus of neonatal rat with HIBD, the expression ofp-ERK and GAP-43 increased significantly compared with sham-operationgroup, and p-ERK increased and peaked earlier than GAP-43, which mightsuggest the activation of ERK could raise the expression of GAP-43.2. FKS06 ameliorated the pathological changes afterhypoxia-ischemia, promoted the physique development of rats with HIBD andincreased the expression of p-ERK and GAP-43, which suggest theneuroprotective effect of it.