Abstract：Objective In the brain, three isoforms of nitric oxide synthase (NOS), namely neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS), have been implicated in biological roles, each isoform exhibiting different roles. This study aims to investigate the effects of lipopolysaccharide (LPS) and dexamethasone on the three isoforms expressions in neonatal rats by using a model of endotoxemia induced by LPS. Methods LPS (5 mg/kg) or LPS (5 mg/kg) plus dexamethasone (10 mg/kg) or sterile saline (controls) was injected intraperitoneally into 68 7-day-old Wistar rats. The rats were sacrificed 2, 4, 6 or 24 hrs after injection respectively. The expressions of NOS isoforms were examined by the immunohistochemical technique. Results nNOS was detected, but in contrast iNOS was not detectable, and eNOS was only faintly expressed in the brain of the controls. The nNOS expression was increased 4 hrs after LPS injection and the iNOS and eNOS expressions were increased 6 hrs after LPS injection. The expressions of the three isoforms reached a peak 24 hrs after LPS injection. Positive immunoreactivity was detected in the cerebral cortex, hippocampus, hypothalamus, paraventricular nucleus and striatum. In addition, nNOS was also detected in the limbic cortex. eNOS or iNOS was faintly expressed in the endothelial cells of cerebral blood vessels. The expressions of three NOS isoforms were remarkably inhibited between 2 and 6 hrs after dexamethasone administration and the inhibition effect continued until 24 hrs after administration. Conclusions nNOS and eNOS may be identified and iNOS is not detectable in the brain of normal neonatal rats. LPS can induce the expressions of three NOS isoforms, and the distribution and intensity of the expressions of three NOS isoforms varies, suggesting that NOS may play roles in the central nervous system development and brain damage in LPS-induced endotoxemia. Dexamethasone has a neuroprotective effect against brain damage induced by endotoxemia.
WANG Hua,DU Xiu-Hua,WU Yu-Bin. Effect of endotoxemia on the expression of nitric oxide synthase in the brain of neonatal rats[J]. CJCP, 2004, 6(3): 203-206.
