Effects of 17beta-estradiol on blood-brain barrier disruption in focal ischemia during GABA(A) receptor inhibition.
Effects of 17beta-estradiol on blood-brain barrier disruption in focal ischemia during GABA(A) receptor inhibition.
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17β-雌二醇对 GABA(A) 受体抑制期间局灶性缺血血脑屏障破坏的影响。
DOI：
10.1055/s-2005-861379
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Weiss,HR
中科院分区：
文献类型：
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作者：
Chi,OZ;Hunter,C;Liu,X;Weiss,HR
本研究旨在探讨γ-氨基丁酸(GABAA)受体抑制能否逆转17-β-雌二醇局灶性脑缺血血脑屏障的破坏作用。在实验前21天，将幼龄去卵巢大鼠植入5 0 0µg 17β雌二醇21d缓释微丸或赋形剂微丸。大脑中动脉(MCA)阻断45min后，每组一半大鼠静脉注射荷包牡丹碱(GABA受体拮抗剂)1 mg/kg/min，2min后再注入0.1 mg/kg/min直至实验结束。另一半则注入等量的生理盐水。测定14C-α-氨基异丁酸的传递系数(KI)和~3H-葡聚糖分布体积(70,000道尔顿)，以衡量大脑中动脉闭塞后1h血脑屏障的破坏程度。空白对照组动物缺血侧大脑皮质Ki(7.2±2.6)µg/g/min高于对侧(2.5±1.4)µg/g/min。荷包牡丹碱注射后，缺血区皮质Ki升高(10.6±5.4)µL/g/min，但差异无统计学意义。在17只β-雌二醇组动物中，缺血区皮质的Ki(3.8±1.6)µg/g/m in低于空白对照组。荷包牡丹碱可显著增加缺血区大脑皮质Ki(14.5±6.8)µL/g/min。在非缺血区皮质，各实验组间KI无显著差异。在缺血区和非缺血区，各实验组右旋糖苷分布体积无明显差异。我们的数据提示，17β-雌二醇治疗后局灶性缺血区血脑屏障破坏减少的部分原因可能是GABAA受体和17β-雌二醇之间的相互作用。
We performed this study to determine whether γ-aminobutyric acid (GABA A) receptor inhibition could reverse the effect of 17β-estradiol on blood-brain barrier (BBB) disruption in focal cerebral ischemia. Young ovariectomized rats were implanted with a 500 µg 17β-estradiol 21-day release pellet or with a vehicle pellet 21 days before the experiments. Forty-five minutes after middle cerebral artery (MCA) occlusion, half of each group was infused with bicuculline (a GABA A receptor antagonist) 1 mg/kg/min for 2 min followed by 0.1 mg/kg/min up to the end of experiments. The other half was infused with the same volume of normal saline. The transfer coefficient (Ki) of 14 C-α-aminoisobutyric acid and the volume of 3 H-dextran distribution (70,000 Daltons) were determined to measure the degree of BBB disruption one hour after MCA occlusion. In the control vehicle-treated animals, the Ki in the ischemic cortex (7.2±2.6 µl/g/min) was higher than in the contralateral cortex (2.5±1.4 µl/g/min). After bicuculline infusion, the Ki in the ischemic cortex increased (10.6±5.4 µl/g/min) although the increase was not statistically significant. In the 17β-estradiol treated animals, the Ki in the ischemic cortex (3.8±1.6 µl/g/min) was lower than control vehicle-treated rats. With bicuculline infusion, the Ki in the ischemic cortex (14.5±6.8 µl/g/min) was markedly increased. In the non-ischemic cortex, there was no significant difference in Ki among the experimental groups. The volume of dextran distribution was not significantly different between the experimental groups in the ischemic or non-ischemic cortex. Our data suggests that part of the reason for the decreased BBB disruption in the focal ischemic area after 17β-estradiol treatment could be due to the interaction between GABA A receptors and 17β-estradiol.