Methylprednisolone exacerbates acute critical illness-related corticosteroid insufficiency associated with traumatic brain injury in rats
Methylprednisolone exacerbates acute critical illness-related corticosteroid insufficiency associated with traumatic brain injury in rats
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甲基泼尼松龙加剧大鼠创伤性脑损伤相关的急性危重疾病相关皮质类固醇不足
DOI：
10.1016/j.brainres.2011.01.045
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发表时间：
2011-03-25
期刊：
影响因子：
2.9
通讯作者：
Zhang, Jianning
中科院分区：
文献类型：
--
作者：
Chen, Xin;Zhang, Bin;Zhang, Jianning
越来越多的证据表明，严重疾病可能导致危重病相关的皮质类固醇不足（CIRCI），并导致预后不良。本研究的目的是测试的假设，甲基强的松龙（MP），合成糖皮质激素，促进创伤后下丘脑和垂体细胞凋亡，导致急性CIRCI和创伤性脑损伤（TBI）的急性期死亡率增加。我们通过测量遭受液压冲击损伤（FPI）并用MP（5-30 mg/kg）治疗的大鼠的急性CIRCI来验证这一假设。使用皮质酮增加指数（CII）评估皮质类固醇对TBI的反应，其中小于2.5的值被认为是急性CIRCI的指示。MP治疗组大鼠的CII与损伤前生理盐水治疗组大鼠的CII相当，但在损伤后第7天接受高剂量MP的损伤大鼠中CII显著降低。同样，伤后第7天，高剂量MP组的急性CIRCI发生率显着更高。此外，与存活大鼠相比，损伤后未存活大鼠的CH显著降低，表明急性CIRCI。我们还研究了细胞凋亡的室旁核（PVN）的下丘脑和腺垂体的垂体，用TUNEL法和透射电镜（TEM）。TUNEL阳性细胞的数量显着较高的损伤大鼠与高剂量MP治疗。在TBI后7或14天，在各实验组的腺垂体中均未检测到TUNEL阳性细胞。然而，对损伤后未能存活的大鼠进行的尸检显示腺垂体中有明显的凋亡细胞。此外，透射电镜观察显示，高剂量MP处理的大鼠的PVN和腺垂体的凋亡特征的形态学变化。这些数据表明，MP治疗TBI可增加下丘脑和垂体中的神经元凋亡，从而加重TBI诱导的急性CIRCI和死亡率。(C)2011 Elsevier B. V.保留所有权利。
Emerging evidence demonstrates that severe illness could induce critical illness-related corticosteroid insufficiency (CIRCI) and cause poor prognosis. The purpose of this study was to test the hypothesis that methylprednisolone (MP), a synthetic glucocorticoid, promotes post-traumatic apoptosis in both the hypothalamus and pituitary, resulting in acute CIRCI and increased mortality in the acute phase of traumatic brain injury (TBI). We tested this hypothesis by measuring acute CIRCI in rats subjected to fluid percussion injury (FPI) and treated with MP (5-30 mg/kg). The corticosteroid response to TBI was evaluated using the corticosterone increase index (CII), where values less than 2.5 were considered indicative of acute CIRCI. The CII of MP treated rats was comparable to that of saline treated control rats before injury but was significantly decreased in injured rats receiving high-dose MP on post-injury day 7. Similarly, the incidence of acute CIRCI was significantly higher in the high-dose MP group on post-injury day 7. Furthermore, the CH of rats that did not survive post-injury was significantly lower compared to that of survival and was indicative of acute CIRCI. We also examined apoptosis in the paraventricular nucleus (PVN) of the hypothalamus and the adenohypophysis of the pituitary, using a TUNEL assay and transmission electron microscopy (TEM). The number of TUNEL-positive cells was significantly higher in injured rats treated with high-dose MP. No TUNEL-positive cells were detected in the adenohypophysis across experimental groups at either 7 or 14 days after TBI. However, autopsies performed on rats that did not survive post-injury revealed obvious apoptotic cells in the adenohypophysis. Moreover, TEM revealed morphological changes characteristic of apoptosis in both the PVN and adenohypophysis of high-dose MP treated rats. These data suggest that MP therapy for TBI could increase neuronal apoptosis in both the hypothalamus and pituitary and consequently exacerbate acute CIRCI and mortality induced by TBI. (C) 2011 Elsevier B.V. All rights reserved.