| The perinatal ischemic brain injury is a significant problem related to Hypoxic–ischemic encephalopathy(HIE), associating with a variety of nervous system diseases, such as cognitive dysfunction, epilepsy, cerebral palsy even neonatal death. Propofol is an intravenous anesthetics widely used in clinic with rapid onset, short duration, quickly and smoothly waking up. Many studies show that propofol can play an important neuroprotective role by reducing glutamate release, increasing uptake of glutamate in hippocampus CA1 region, and reducing the number and affinity of glutamate receptor, lipid peroxidation and apoptosis of hippocampus neural cells in cerebral ischemia rats. Clinical research has also shown that propofol has neuroprotective effects on cerebral injury patients. We have not yet found any report about the neuroprotective effects of propofol on ischemic fetal rat brain in China and controversial reports about it from other counties are limited. The aim of this study was to observe the neuroprotective effect of propofol on intrauterine distress fetal rat brain.Objective: To observe the neuroprotective effect of different doses propofol on ischemic fetal rat brain and to explore the mechanisms of neuroprotective effect of propofol.Method: Healthy SD rats 18 of female and 6 of male, weighing 240-280 g, were used in this study. Got pregnant rats by bleeding them under laboratory condition. Experiment were performed at the 18 day of pregnancy. Group S: sham operation group, Group IR: ischemia reperfusion group, Group P1-P3: low, medium and high doses of propofol groups, Group B: bicuculline group. In group S and group IR, 1ml saline solution was administered via caudal vein when the rats were awake. In group P1-P3, 10, 30, 50mg/kg of propofol was administered via caudal vein respectively. In group B, when 50mg/kg propfol was administered via caudal vein, 5mg/kg bicuculline was injected intraperitoneally at the same time. After adequate anesthesia with 10% chloral hydrate, the pregnant rats were placed in the supine position and laparotomies were performed. Bilateral uterine ovarian arteries were clamped for 11 min to make intrauterine distress model of the fetal rats. The brains of fetal rats were removed after 3 days of reperfusion. Brain sections were cut, mounted and stained with HE staining. The profile of the hippocampus CA1 was evaluated under a light microscope and neuronal Lesion-index(LI%) was calculated. MDA content of fetal rat brain was detected by thiobarbituric acid reaction method to determine the lipid peroxidation degree of brain.Results: Compared with that in group S, most neurons in hippocampus CA1 area were injured, LI% was significantly increased(P<0.01), and the content of MDA was significantly increased(P<0.01) in group IR. Compared with that in group IR, LI% was significantly decreased(P<0.01), and the content of MDA was significantly reduced(P<0.01) in all propofol groups. There was no significant difference between group P2 and P3(P>0.05). LI% and the content of MDA in group B significantly decreased compared with that in group IR(P<0.01), but were higher than that in propofol groups.Conclusion: Propofol can protect the neurons in hippocampus CA1 region of fetal rat brain against intrauterine distress and reduce the concentration of MDA in the brain. The optimal dose for neuroprotection may be 30mg/kg for propofol at higher doses don’t show more neuroprotective effect. Bicuculline, a kind of GABA receptor antagonist, could partially reverse the neuroprotective effect of propofol. |
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