绝经后女性急性缺血性脑卒中后 P450 芳香化酶水平升高。
Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke.
机构信息
Department of Neurology and Neuroscience, University of Texas, Houston, TX, USA.
University of Connecticut Health Center, Farmington, CT, USA.
出版信息
Biol Sex Differ. 2021 Jan 7;12(1):8. doi: 10.1186/s13293-020-00357-w.
BACKGROUND
Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes.
METHODS
Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 h of symptom onset. 17β-estradiol, testosterone, and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as the difference of premorbid and discharge mRS) using multivariate regression.
RESULTS
We found no significant difference in estradiol levels 24 h after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs. 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27 ± 0.22 vs. 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with change in mRS in both women (r = 0.38, p = 0.02) and men (r = 0.3, p = 0.04).
CONCLUSIONS
Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 h) of stroke. However, no significant difference in estradiol levels is seen 24 h post-stroke in men or women. Testosterone levels decrease at 24 h after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.
背景
性别差异在中风中的作用归因于雌激素的神经保护作用，但大多数雌激素补充预防中风的临床试验都失败了。 性激素对中风结果的影响仍然存在争议。 睾丸酮在神经组织中转化为雌二醇导致性别分化。 新出现的数据表明，芳香化酶活性在脑损伤时增加，并且在动物模型的缺血半影区中可见增加的芳香化酶表达。 本研究的目的是检查急性缺血性中风后内源性性激素的水平，并确定性激素水平是否与急性中风结果相关。
方法
在症状发作后 24 小时内，根据批准的 IRB 从缺血性中风患者和对照者的外周血中采集血液。 用 ELISA 法测量男性和女性血清中的 17β-雌二醇、睾丸酮和芳香化酶水平。 在中风和对照组中比较男性与女性的激素水平，并使用多元回归分析将激素水平与结局（NIHSS 和改良 Rankin 量表的变化（mRS），定义为发病前和出院时 mRS 的差异）进行相关性分析。
结果
我们发现男性中风后 24 小时雌二醇水平无显著差异（p = 0.86）或女性（p = 0.10）。 与对照组相比，男性中风后睾酮明显下降（1.83 ± 0.12 对 2.86 ± 0.65，p = 0.01）。 与对照组相比，女性中风后芳香化酶水平明显升高（2.27 ± 0.22 对 0.97 ± 0.22，p = 0.002），但男性无显著差异（p = 0.84）。 女性（r = 0.38，p = 0.02）和男性（r = 0.3，p = 0.04）中风后雌二醇水平与 mRS 的变化呈正相关。
结论
雌二醇水平与两性的功能结局（mRS 的变化）相关，至少在中风的急性阶段（24 小时）如此。 然而，男性或女性中风后 24 小时内雌二醇水平没有明显差异。 男性中风后 24 小时睾酮水平下降。 与动物模型一样，芳香化酶水平在急性缺血性中风后增加，但这仅适用于女性。 这些表明绝经后妇女在急性缺血性中风后存在活跃的芳香化酶过程。
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