RESUMEN
Objective To study the mechanism of interaction between neuronal nitric oxide syn-thase (nNOS) and inducible nitric oxide synthase (iNOS) following traumatic brain injury (TBI) in rats. Methods A total of 250 male Wistar rats were randomly divided into five groups, ie, sham oper-ation group, trauma group, 7-nitroindazole (7-NI) treatment group, aminoguanidine (AG) treatment group and combined AG and 7-NI treatment group. Severe closed TBI was made by using Marmarou meth-od. Protein expressions of nNOS and iNOS in hippocampus CAI were detected by means of immunohisto-chemical staining at 1,3, 6, 12 hours and at days 1,3, 7 and 14 after TBI. Results The expression of nNOS reached a peak at 6 hour after injury in all groups, with no statistical difference between groups (P > 0. 05), when there was no statistical difference between 7-NI treatment group and trauma group (P > 0. 05) but statistical difference in AG treatment group and combined AG and 7-NI treatment group compared with trauma group at 12 hours after TBI (P <0.05). The expression of iNOS reached maximal level at day 3 after TBI, with lower level in 7-NI group, AG treatment group and combined AG and 7-NI treatment group compared with trauma group (P < 0.05). Conclusions After TBI, nNOS interacts with iNOS by means of the feedback of nitric oxide. The enhanced expression of nNOS is initial factor for increase of iNOS expression, which can down regulate the expression of iNOS.
RESUMEN
Objective To explore the mechanism of neurotoxic effects of neuron nitric oxide synthase(nNOS)and inducible nitric oxide synthase(iNOS),and the therapeutic effects of 7-nitroindazole(7-NI)and aminoguanidine(AG),in traumatic brain injury(TBI)rats.Methods Two hundred and fifty adult male Wistar rats were randomly divided into 5 groups:sham operation group,traumatic group,AG group,7-NI group and AG+7-NI group.Animals in each group were divided into 8 subgroups according to the time after trauma(1,3,6,12 hours and 1,3,7,14 days).Severe diffused brain injury model was made with Marmarou method.Expressions of nNOS and iNOS in hippocampus CA1 region were determined by immunohistochemistry,nerve cells apoptosis in hippocampus CA1 region was observed by TUNEL methods,and the relationship between apoptosis and NOS was observed by double staining.Results In trauma group,the expression of nNOS in hippocampus CA1 region peaked at 6h post-trauma,the expression of iNOS and apoptosis of nerve cells in hippocampus CA1 region both peaked at 3d post-trauma,while the apoptosis was alleviated in AG group,7-NI group and AG+7-NI group.The number of both TUNEL staining and nNOS immunostaining positive cells increased at 6h post-trauma in trauma group,significantly higher than that in 7-NI group.The number of both TUNEL staining and iNOS immunostaining positive cells increased at 3d post-trauma in trauma group,significantly higher than that in AG group.Conclusions The over-expression of nNOS and iNOS has toxic effects to neural tissues of brain,serves as one of the factors inducing nerve cell apoptosis in hippocampus CA1 region.7-NI and AG can inhibit the expression of nNOS and iNOS,reduce the nerve cell apoptosis,and play an important role in neuroprotective effect.