EFFECTS OF SELECTIVE NITRIC OXIDE SYNTHASE SUBTYPE INHIBITORS ON THE HYPOXIC-ISCHEMIC CEREBRAL INJURIES IN NEWBORN RATS

Yang M1, Zhao L2

1 Beijing Children’s Hospital Affiliated to Capital University of Medical Sciences. Beijing, China

2 The 1st affiliated Hospital of Jiangxi Medical University, Nanchang, Jiangxi, China

 

Objective: To observe the effects of different NOS inhibitors administered in the HIE model rats on the hypoxic-ischemic cerebral injury and study the probable mechanism, providing experimental basis for the clinical application of NO and its relative agents

Methods: The models of HIE were established in newborn rats. Taking SOD, MDA as the indices of the severity of cerebral injuries, we observed the changes of NO, SOD, MDA in brain tissue after administering selective or nonselective NOS inhibitors, and analyzed the different correlativity between NO and SOD, MDA when the derivation and concentration of NO were different. Pathologic changes of brain tissue were documented.

Results: The NO concentration rose after the rats underwent HI, which had certain fluctuating patterns, accompanied with the decrease of SOD and the increase of MDA. Both L-NAME and AG can reduce the NO concentration, but the extent and time phase were different. L-NAME did not have significant protective effect on HI in early stage (<8hr), but in later stage (24hr) it did. However AG showed a good protective effect during the whole stage. There were certain correlativity between NO and SOD,MDA in AG group.

Conclusions: To some extent and during certain time phase, the derivation of NO may have a closer relationship with SOD ,MDA than the concentration. The expression of cNOS in the early stage of HI can protect the cerebra against injuries, but the excessive expression of iNOS may result in cerebral injuries in later stage. Selective inhibitors of iNOS can alleviate the oxygen-derived free radical injuries of cerebra after HI.

Key words: Nitric oxide, Enzyme inhibitor, Cerebral anoxia, Cerebral ischemia SOD, MDA

 
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