大鼠TBI后急性期下丘脑-垂体-肾上腺轴损害和功能改变的意义研究
Significance of changes in hypothalamic-pituitary-adrenal axis damage and function after TBI in rats
摘要目的探讨重型颅脑创伤(TBI)大鼠急性期下丘脑?垂体?肾上腺轴损害和功能改变对神经功能、学习记忆功能的影响作用。方法选取成年健康雄性SD大鼠60只,随机分为假手术组、模型组和地塞米松组各20只,模型组和地塞米松组大鼠采用Feeney法制备大鼠TBI模型,地塞米松组大鼠与伤后10 min、24、48、72 h腹腔注射地塞米松0.6 mg/kg,其余2组给予等量生理盐水处理,分别检测并比较3组大鼠伤后3、12、24、72 h的外周血皮质酮、促肾上腺皮质激素(ACTH)水平及神经细胞凋亡情况的变化,并观察3组大鼠伤后1、7d的神经功能评分、伤后第7天的水迷宫实验结果差异。结果模型组和地塞米松组大鼠伤后不同时间外周血皮质酮、促肾上腺皮质激素水平、水迷宫潜伏期和神经细胞凋亡程度较假手术组均有明显升高(P<0.05),但地塞米松组伤后外周血皮质酮、促肾上腺皮质激素水平明显高于模型组(P<0.05),水迷宫潜伏期和神经细胞凋亡程度明显低于模型组(P<0.05);模型组和地塞米松组大鼠伤后不同时间水迷宫实验象限百分率较假手术组均有明显降低(P<0.05),但地塞米松组伤后水迷宫实验象限百分率明显高于模型组(P<0.05)。结论 TBI大鼠急性期下丘脑?垂体?肾上腺功能发生改变,皮质酮与ACTH水平升高,这可能与神经功能、学习记忆功能损害具有一定的关系。
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abstractsObjective To investigate the effect of acute?phase hypothalamic?pituitary?adrenal axis damage and function on neurological function,and learning and memory at the acute phase in rats with severe traumatic brain injury(TBI). Methods Sixty healthy male adult SD rats were randomly divided into sham operation group, model group and Dexamethasone group (n=20 each). The model group and Dexamethasone group were treated with Feeney method,and the rat TBI models were established. The Dexamethasone group was injected with 0.6 mg/kg Dexamethasone intraperitoneally at 10 min,24,48 and 72 hours after injury. The other two groups were treated with equal volume of normal saline. The changes on the levels of peripheral blood corticosterone,adrenocorticotropic hormone(ACTH)and neuronal apoptosis at 3,12,24 and 72 hours after the injury were measured and compared among the three groups. The differences in the neurological scores at 1 and 7 d after the injury,and the findings of the water maze test at 7 days after the injury were determined. Results The levels of peripheral blood corticosterone,ACTH,water maze latency,and neuronal apoptosis at the different time points after the injury in the model group and Dexamethasone group were significantly increased (P<0.05). The levels of peripheral blood corticosterone and ACTH after the injury in the Dexamethasone group were significantly higher than those in the model group(P<0.05),whereas the water maze latency and neuronal apoptosis were significantly lower than those in the model group(P<0.05). The percentage of water maze quadrant at different time points after the injury in the model group and Dexamethasone group was significantly lower than that in the sham operation group (P<0.05),whereas the percentage of water maze quadrant after the injury in the Dexamethasone group was significantly higher than that in the model group (P<0.05). Conclusion Changes in the hypothalamic?pituitary?adrenal axis function at the acute phase in rats with TBI are found that the levels of corticosterone and ACTH are increased. It may be related to the damage of neurological function,and learning and memory.
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