| Hypoxic-ischemic encephalppathy (HIE) is the sevious complication of neonatal asphsyxia, which is a major cause of high mortality and chronic neurological in survivors, such as mental retardation, epilepsy, cerebral palsy, spasm and incoordination.The possible mechanism may be closely related to effects of cellular energy failure, acidosis, excitatory amino acid neurotoxity and reperfusion injury. How to prevent and cure hypoxic-ischemic brain injury of perinatal stage effectively, decrease death or mayhem rate is badly in need in clinic.In 1991, Barks found pretreatment with DEX could relieve hypoxic-ischemic brain injury of neonatal animals,and the neuroprotective effects are dose- and time-dependent. But the mechanism is not clear. Recently, it was proved that there are two patterns of cell death in HIBD, apoptosis and necrosis,in which apoptosis is more important, its peaking time occurrenc at 24 h~72 h after cerebral hypoxia-ischemia. According to this, the experiment isVItrying to investigate the effect of DEX on neural apoptosis so as to elucidate the possible mechanism of its neuroprotective effect.Section one: The protective effect of pretreatment with DEX on HIBD in ratsObjective To study the protective effect of pretreatment with DEX against HIED in rats. Methods 7-day-old Sprague-Dawley(SD) rats were used as research subject and randomly divided into 5 groups (l)control group(n=ll), (2)sham group(n=ll), (3)HIBD group(n=12), (4)Pretreatment with DEX group(n=12), (5)Treatment with DEX group(n=12). Making HIBD model in 7-day-old,measuing body weight,left/right brain weight ratio , brain neuropathology and neural apoptosis 7 days after HI. Results 1.Weight increasing. The weight increased obviously slowly in HIBD group. At 7 days after HI, the body weight only increased (9.58?.38)g, the increasing rate was (71.94 + 22.56)%, compared with control, sham and pretreatment with DEX group respectively ,there were statistical significance between them (P < 0.01). But there were no stastitical significance between HIBD group and treatment with DEX groupCP > 0.05).2. Left/right brain weight ratio. At 7 days after HI,the left/right brain weight ratio decreased to (0.8434 ?.0880), compared with control, sham and pretreatment with DEX group respectively, there were statistical significance between them (P < 0.01). 3. Neuropathology and apoptosis. HE staining showed no obviousVIIabnormity in control and sham group. There was selective neuronal cell death and neuron damage of ipsilateral hemisphere in HIBD group, cell derangment, neuronal degeneration and amounts of neural apoptosis could be seen . The degree of neuron damage were alleviated obviously in pretreatment with DEX group, neural apoptosis decreased significantly. Conclusion There is a protective effect against HIBD in rats with pretreatment of DEX.Section two: The mechanism of protective effect with DEX against HIBD in ratsObjective To investigate the activity of NF-KB in brain after HI in neonatal rats and the effects of DEX on neuronal apoptosis so as to elucidate the possible mechanism of DEX against HIBD in rats. Methods 7-day-old Sprague-Dawley(SD) rats were used as research subject and randomly divided into 5 groups (l)control group(n=8), (2)sham group(n=8), (3)fflBD group(n=8), (4)Pretreatment with DEX group(n=9), (5)Treatment with DEX group(n=9). Making HIBD model in 7-day-old, Measuring WBa with Western blot method measuring P65, cell apoptosis with immunochemistry methods and TUNEL respectively at 72h after HI. Results 1. TUNEL positive cell. TUNEL positive cells were only seen occasionally in control and sham groups. There are amounts of apoptosis cells in HIBD group(384.38?2.03),compared with pretreatment with DEX group, there was a statiscal significance between them(? < 0.01). But no stastical significance between HIBD and treatment with DEX group(P > 0.05). 2. P65 positive cells (nuclearVIIItransition cells). P65 positive cells were only seen occasionally in control and sham groups.
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