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雌激素和孕激素单独和联合应用对创伤性脑损伤后细胞因子浓度的调节作用。

The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury.

机构信息

Neuroscience Research Center, Kerman University of Medical Sciences, Iran.

出版信息

Can J Physiol Pharmacol. 2011 Jan;89(1):31-40. doi: 10.1139/y10-103.

DOI:10.1139/y10-103
PMID:21186375
Abstract

Cytokines play an important role in the pathophysiology of traumatic brain injury (TBI). This study was designed to determine the effects of administering progesterone (P) and estrogen (E), alone and in combination, on brain water content, blood-brain barrier (BBB) disturbance, and brain level of cytokines following diffuse TBI. Ovariectomized rats were divided into 9 groups, treated with vehicle, E1, E2, P1, P2, E1+P1, E1+P2, E2+P1, and E2+P2. Levels of BBB disruption (5 h), cytokines, and water content (24 h) were evaluated after TBI induced by the Marmarou method. Physiological (E1 and P1) and pharmacological (E2 and P2) doses of estrogen and progesterone were administered 30 min after TBI. Water content in the E1+P2-treated group was higher than in the E1-treated group. The inhibitory effect of E2 on water content was reduced by adding progesterone. The inhibitory effect of E1 and E2 on Evans blue content was reduced by treatment with E1+P1 and E2+P2, respectively. The brain level of IL-1β was reduced in E1 and E2, after TBI. In the E2+P2-treated group, this level was higher than in the E2-treated group. The brain level of TGF-β was also elevated by the administration of progesterone and estrogen alone, and reduced when the hormones were administered in combination. In conclusion, a combined administration of progesterone and estrogen inhibited the decreasing effects of administration of progesterone and estrogen alone on water content and BBB disruption that mediated to change the proinflammatory cytokines.

摘要

细胞因子在创伤性脑损伤 (TBI) 的病理生理学中发挥着重要作用。本研究旨在确定单独和联合给予孕激素 (P) 和雌激素 (E) 对弥漫性 TBI 后脑水含量、血脑屏障 (BBB) 紊乱和脑内细胞因子水平的影响。将去卵巢大鼠分为 9 组,分别用载体、E1、E2、P1、P2、E1+P1、E1+P2、E2+P1 和 E2+P2 处理。Marmarou 法诱导 TBI 后 5 h 评估 BBB 破坏程度(5 h),24 h 评估细胞因子和水含量。TBI 后 30 min 给予生理 (E1 和 P1) 和药理 (E2 和 P2) 剂量的雌激素和孕激素。E1+P2 治疗组的水含量高于 E1 治疗组。添加孕激素可降低 E2 对水含量的抑制作用。用 E1+P1 和 E2+P2 处理分别降低了 E1 和 E2 对 Evans 蓝含量的抑制作用。TBI 后,E1 和 E2 可降低脑内 IL-1β 水平。在 E2+P2 治疗组中,该水平高于 E2 治疗组。单独给予孕激素和雌激素可升高脑内 TGF-β 水平,而联合给予时则降低。总之,孕激素和雌激素的联合给药抑制了孕激素和雌激素单独给药对水含量和 BBB 破坏的降低作用,从而改变了促炎细胞因子。

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