【摘要】：目的：通過(guò)建立大鼠急性有機(jī)磷中毒（AOPP）模型，研究缺氧誘導(dǎo)因子-1(HIF-1)在腦組織中的表達(dá)和血清中丙二醛（MDA）含量的變化，，以及高壓氧對(duì)它們的干預(yù)作用，探討高壓氧防治急性有機(jī)磷中毒性腦損傷的作用及其機(jī)制，為拓展高壓氧治療的范圍提供理論依據(jù)。 方法：健康雄性SD大鼠60只，隨機(jī)分為正常對(duì)照組、中毒組、常規(guī)治療組和高壓氧治療組，正常對(duì)照組6只，其余3組各18只。中毒組、常規(guī)治療組和高壓氧治療組分3個(gè)時(shí)間點(diǎn)（建模后1，3，7h）進(jìn)行標(biāo)本采集，每個(gè)時(shí)間點(diǎn)各6只。采用頸背部皮下累計(jì)注射法造模，每次敵敵畏用量4mg/kg，共注射5次，保證大鼠不間斷抽搐3小時(shí)。常規(guī)治療組在造模后立即予長(zhǎng)托寧0.12mg/kg、氯解磷定30mg/kg大腿外側(cè)肌肉注射，高壓氧治療組在常規(guī)治療之后即行高壓氧治療，正常對(duì)照組注射等容量的生理鹽水。各組在造模完成后1、3、7h處死大鼠，下腔靜脈取血，離心分離血清，采用硫代巴比妥酸比色法試劑盒檢測(cè)MDA的含量；斷頭取腦，大腦皮層放入4％的多聚甲醛中固定，石蠟包埋、切片，HE染色、尼氏染色觀察腦組織病理改變及IHC檢測(cè)HIF-1蛋白表達(dá)；海馬組織用于熒光定量PCR檢測(cè)HIF-1mRNA的表達(dá)。所得數(shù)據(jù)用SPSS19.0軟件統(tǒng)計(jì)分析。 結(jié)果：與中毒組相比，高壓氧治療組的腦組織病理?yè)p傷有所減輕。中毒組各時(shí)間點(diǎn)，腦組織HIF-1的表達(dá)和血清MDA含量都依次增高，顯著高于正常對(duì)照組（P0.05）；經(jīng)高壓氧治療后，腦組織HIF-1的表達(dá)和血清MDA含量逐漸下降（P0.05），也低于常規(guī)治療組1h、3h（P0.05）。相關(guān)分析發(fā)現(xiàn)，HIF-1mRNA相對(duì)表達(dá)量與血清MDA含量（r=0.909，P=0.000）具有顯著的正相關(guān)性。 結(jié)論：高壓氧對(duì)急性有機(jī)磷中毒性腦損傷的保護(hù)作用優(yōu)于常規(guī)治療組，其作用機(jī)制與抗氧化損傷和抑制HIF-1的表達(dá)有關(guān)；且高壓氧干預(yù)越早越好。
[Abstract]:Objective: to establish (AOPP) model of acute organophosphorus poisoning in rats, to study the expression of hypoxia inducible factor 1 (HIF-1) in brain tissue and the change of malondialdehyde (MDA) content in serum, and the effect of hyperbaric oxygen on it. To investigate the effect of hyperbaric oxygen on acute organophosphorus poisoning brain injury and its mechanism, and to provide theoretical basis for expanding the range of hyperbaric oxygen therapy. Methods: sixty male Sprague-Dawley rats were randomly divided into normal control group, poisoning group, routine treatment group and hyperbaric oxygen treatment group, normal control group (n = 6), and other 3 groups (n = 18 each). Poisoning group, routine treatment group and hyperbaric oxygen treatment group were collected at three time points (1: 3 hours after modeling), 6 rats in each time point. The model was made by subcutaneous injection of dichlorvos at a dose of 4 mg / kg for 5 times in order to ensure continuous convulsion in rats for 3 hours. The routine treatment group was treated with Changtonin 0.12 mg / kg immediately after the model was established, and 30mg/kg was injected intramuscularly on the lateral side of thigh. The hyperbaric oxygen group was treated with hyperbaric oxygen immediately after routine treatment, and the normal control group was injected with normal saline of the same volume. The rats in each group were killed at 1: 3h after modeling, blood was collected from inferior vena cava, serum was isolated by centrifugation, the content of MDA was detected by thiobarbituric acid colorimetric kit, the brain was taken off the head, the cerebral cortex was fixed in 4% polyformaldehyde, and embedded in paraffin. The pathological changes of brain tissue and the expression of HIF-1 protein were detected by IHC, and the expression of HIF-1mRNA was detected by fluorescence quantitative PCR in hippocampal tissue. The data were analyzed by SPSS19.0 software. Results: compared with the poisoning group, hyperbaric oxygen treatment group reduced the pathological injury of brain tissue. At each time point, the expression of HIF-1 and the content of serum MDA in the poisoning group increased in turn, which were significantly higher than those in the normal control group (P0.05); after hyperbaric oxygen treatment, the expression of HIF-1 and the content of serum MDA decreased gradually (P0.05), and were also lower than those in the routine treatment group for 1 hour and 3 hours (P0.05). Correlation analysis showed that there was a significant positive correlation between the relative expression of HIF-1 mRNA and the level of serum MDA (r 0.909 Pu 0.000). Conclusion: the protective effect of hyperbaric oxygen on acute organophosphorus poisoning brain injury is better than that of routine treatment group, and its mechanism is related to antioxidant damage and inhibition of HIF-1 expression, and hyperbaric oxygen intervention is better as early as possible.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R595.4

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