THE EFFECTS OF NITRIC
OXIDE SYNTHASE INHIBITORS ON APOPTOSIS OF NEURONS AFTER HYPOXIC-ISCHEMIC
BRAIN DAMAGE IN NEONATAL RATS
Yu HM1, Yao Y2, Du
LZh1, Yu ZhSh1, Sun MY1
1 Affiliated Children¡¯s
Hospital, 2Affiliated Second Hospital, Zhejiang University
School of Medicine, Hangzhou, China
Objective: To study the effects of
three different kinds of nitric oxide synthase inhibitors
(N-omega-nitro-L-arginine methylester, L-NAME; Aminoguanidine, AG;
7-nitroindazole, 7-NI) on apoptosis of neurons after hypoxic-ischemic brain
damage (HIBD) in neonatal rats.
Methods: The HIBD model was
produced in the 7-day postnatal SD rats which were subjected to permanent
unilateral carotid artery ligation followed by an hypoxic insult of 2
hours. L-NAME, AG, 7-NI and PBS were administered after HIBD respectively.
Neuronal apoptosis was examined using Hematoxylin and Eosin (HE) staining,
TUNEL staining and transmission electron microscopy 24 hours later.
Results: Morphological
characteristic changes of apoptosis in different stages were revealed. The
number of apoptosis in hippocampus and cortex in the 7-NI group 24h after
HIBD was significantly lower than that in the PBS group (p<0.005). The
number of apoptosis between the AG and the PBS groups in cortex. The number
in hippocampus and cortex in the L-NAME group was not significantly
different from that in the PBS group (p>0.05).
Conclusion: This study demonstrates
that apoptosis plays important role in the delayed neuronal death after
HIBD, and first proved it is selective NOS inhibitors (7-NI and AG) not
nonselective NOS inhibitor (L-NAME) that show their anti-apoptosis effects
on HIBD.