亚低温联合异氟醚后处理减少大鼠脑缺血再灌注损伤及对STAT3表达的影响

发布时间：2018-09-11 20:20

【摘要】：目的:观察大鼠局灶性脑缺血再灌注损伤及p-STAT3的表达情况以及实施亚低温和异氟醚处理后的变化,探讨亚低温和异氟醚联合治疗的脑保护作用及其可能的作用机制。方法:健康雄性成年SD大鼠(Sprague-Dawley rats,SDrats)50只,体重250-300g,随机分为5组(n=10),假手术组(Sham组)仅切开皮肤,不留置线栓;模型组(ischemia-reperfusion,I/R组)线栓法造大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型;亚低温组(mild hypothermia,MH组)、异氟醚后处理组(isoflurane,Iso组)分别术中持续头部亚低温至再灌注结束、缺血再灌注后异氟醚治疗1小时。亚低温异氟醚联合治疗组(MH+Iso组)联合两种治疗方法。于再灌注24 h后进行神经功能缺陷评分(neurological deficit scores,NFC),各组取5只大鼠处死,取脑组织,2,3,5-三苯基氯化四氮唑(2,3,5-Triphenyltetrazolium chloride,TTC)染色法测定脑梗死体积;另外每组处死5只大鼠,取脑组织缺血皮层,免疫印迹(Western blotting,WB)检测细胞蛋白表达情况,并测定p-STAT3和t-STAT3的蛋白表达水平。结果:1)与I/R组比较,MH组、Iso组、MH+Iso组神经功能缺损评分明显降低(P0.01),脑梗死体积显著缩小(P0.01),p-STAT3/t-STAT3明显减少(P0.01)。2)与MH组、Iso组相比,MH+Iso组神经功能缺损评分降低(P0.05),脑梗死体积缩小(P0.05),p-STAT3/t-STAT3明显减少(P0.05)结论:亚低温联合异氟醚后处理能显著减少大鼠脑缺血再灌注损伤程度,效果优于单独亚低温或异氟醚后处理治疗,其机制可能是亚低温联合异氟醚后处理抑制星型胶质细胞和小胶质细胞酪氨酸激酶2(Janus kinase,JAK2)/转录因子3(signal transducer and activator of transcription3,STAT3)信号转导通路的表达,随后抑制星型胶质细胞或小胶质细胞激活和增殖,起到脑缺血再灌注保护作用。
[Abstract]:Aim: to observe the expression of p-STAT3 and the changes of focal cerebral ischemia-reperfusion injury in rats after mild hypothermia and isoflurane treatment, and to explore the protective effect of mild hypothermia and isoflurane on brain and its possible mechanism. Methods: 50 healthy male adult SD rats (Sprague-Dawley rats,SDrats), weighing 250-300g, were randomly divided into 5 groups: sham operation group (Sham group), sham-operated group (Sham group), model group (ischemia-reperfusion,I/R group), middle cerebral artery occlusion (middle cerebral artery occlusion,MCAO) model. Mild hypothermia group (mild hypothermia,MH group) and isoflurane post-treatment group (isoflurane,Iso group) continued mild hypothermia until the end of reperfusion during operation. Isoflurane was treated with isoflurane for 1 hour after ischemia-reperfusion. Mild hypothermia isoflurane combined treatment group (MH Iso group) combined with two treatment methods. After 24 hours of reperfusion, the neurological deficit score (neurological deficit scores,NFC) was used. Five rats in each group were killed, and the cerebral infarct volume was determined by the method of 2-titration 3-triphenyltetrazolium chloride,TTC staining, and 5 rats were killed in each group, and the ischemic cortex of the brain tissue was taken. Western blot (Western blotting,WB) was used to detect the expression of p-STAT3 and t-STAT3. Results compared with the I / R group, the neurological impairment score and the infarct volume of the MH / Iso Iso group were significantly decreased (P0.01), and the volume of cerebral infarction was significantly reduced (P0.01). Compared with the MH group (P0.01), the neurological function defect score of the MH-Iso group decreased (P0.05), the cerebral infarction volume decreased (P0.01), and the cerebral infarct volume shrank significantly (P0.01) in comparison with that in the MH group (P0.01). Conclusion: mild hypothermia combined with isoflurane can significantly reduce the degree of cerebral ischemia-reperfusion injury in rats. The effect is better than that of mild hypothermia or isoflurane treatment alone. The mechanism may be that mild hypothermia combined with isoflurane post treatment inhibits the expression of tyrosine kinase 2 (Janus kinase,JAK2) / transcription factor 3 (signal transducer and activator of transcription3,STAT3 signal transduction pathway in astrocytes and microglia. Subsequently, it inhibited the activation and proliferation of astrocytes or microglia, and played a protective role in cerebral ischemia reperfusion.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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