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Neuro-protective Effects Of ω-3 Fish Oil Emulsion And Hypothermia On Hypoxic-ischemic Brain Damage In Neonatal Rats

Posted on:2016-02-24Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y LiFull Text:PDF
GTID:2284330464958594Subject:Academy of Pediatrics
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Background Hypoxic-ischemic encephalopathy (HIE) caused by neonatal asphyxia is one of the most important causes of delayed neurological development. Tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) play an important role in neonates with hypoxic-ischemic brain damage, the high levels of IL-6 and TNF-a may have evoked an inflammatory response cascade and caused further damage in the brain. At present treatment for patients with HIE are limited, Hypothermia is an effective method for reducing the neuronal damage induced by HIE. With an improved understanding of the numerous pathways that are activated by HIE, it seems highly unlikely that any single treatment (that affects one or more branch points of any one pathway) could alter outcomes. It is much more logical to combine multiple potent treatments (modulating numerous key pathways) in an effort to achieve synergistic effects.Fish oil fat emulsion consist mainly of eicosapentaenoic acid (EPA) and docosahenaenoic acid (DHA), they are omega-3 fatty acids. Fish oil fat emulsion can provide energy, at the same time it can regulate the expression of inflammatory mediators, improve immunity, it is attractive candidates for post-HI therapy in combination with hypothermia. It was reported abroad that the effectiveness of DHA in neonatal rats with moderate -to-severe hypoxic-ischemic brain damage. However, little research has been done in the Fish oil fat emulsion.Objective To determine if ω-3 fish oil emulsion and/or mild hypothermia have the protective effects on hypoxic-ischemic brain damage in neonatal rats and its mechanisms.Methods 210 neonate rats were randomly allocated to five groups:sham operation group(A), control group (B), fish oil group (C), hypothermia group (D), fish oil and hypothcrmia group(E). each group has 42 rats. After 24 h,3d,7d were measured respectively the levels of IL-6、TNF-α、NSE, histological changes in brain tissue were observed with electron microscope;four separate reflexes were evaluated at 24h, the weight changes at 7d and the percentage of dead neurons at 3d.Results1. Behavioral changes:The rats appeared cyanosis, poor response, incontinence, etc, part of the rats can appear recognizant obstacle and deaths during the process of hypoxic ischemia(HI). The B group rats showed poor response, uncoordinated movement, and the rats’s head was rotated to the left in fixed position, the C group and D group rats showed spiritual good response, but walking unstable. The E group rats’s performances were close to the A group.2. Brain tissue pathological:HE staining showed the neurons damage in B group were more serious than those in C group and D group. There was no obvious abnormity found in the A and E group.3. The weight and the evaluation on four reflections were improved in group C、D and E (P<0.05), the most obvious changes were observed in group E (P<0.05)4. inflammatory factors changes:The content of TNF-a and IL-6 were increased after hypoxic ischemia at 24h and 3d, they were back to normal at 7d. The content of TNF-a and IL-6 were significantly down-regulated in C group, D group and E group compared with those in B group(P<0.05), the most obvious changes were observed in group E(P<0.05).5. brain damage changes:The content of NSE was down-regulated in C group, D group and E group compared with those in B group (P<0.05), the most obvious changes were observed in group E (P<0.05), The content of NSE in group E was neared it in group A at 3d (P>0.05). The percentage of dead neurons were significantly increased in group B compared with group A (P<0.05), they were improved in group C, D and E (P<0.05), The most obvious changes were observed in group E(p<0.05).Conclusion1. ω-3 fish oil emulsion and/or mild hypothermia have protective effects on hypoxic-ischemic brain damage, especially when ω-3 fish oil emulsion and mild hypoth-ermia are used simultaneously.2. ω-3 fish oil emulsion and/or mild hypothermia have protective effects on hypoxic-ischemic brain damage through change the content of TNF-α and IL-6.
Keywords/Search Tags:ω-3 fish oil emulsion, hypothermia, hypoxic-ischemia brain damage, tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)
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