Ingberg Edvin, Theodorsson Elvar, Theodorsson Annette, Ström Jakob O
Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Division of Neuroscience, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland.
Sci Rep. 2016 Feb 3;6:20228. doi: 10.1038/srep20228.
The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.
众多关于雌激素对脑缺血影响的动物研究中，大多数报告了神经保护作用的结果，但也有少数研究显示损伤增加。激素给药方法的差异导致17β-雌二醇水平差异很大，这可能解释了先前报道的效应差异。本研究的目的是检验这样一个假设：决定效应的是给药剂量本身，而非给药途径和方法，高剂量具有损害作用，而低剂量具有保护作用。120只去卵巢雌性Wistar大鼠（每组n = 40只）被随机分为三组，皮下注射不同剂量的17β-雌二醇，然后进行短暂性大脑中动脉闭塞。24小时后进行改良胶带试验，随后处死大鼠以测量梗死面积。与我们的假设相反，发现17β-雌二醇剂量与梗死面积之间存在显著负相关（p = 0.018）。因此，没有证据支持17β-雌二醇仅取决于剂量就既能具有神经保护作用又具有神经毒性的假设。事实上，相反的是，研究结果表明17β-雌二醇剂量越高，梗死面积越小。
