Differential effects of 17β-estradiol upon stroke damage in stroke prone and normotensive rats
Differential effects of 17β-estradiol upon stroke damage in stroke prone and normotensive rats
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DOI：
10.1097/01.wcb.0000112322.75217.fd
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发表时间：
2004-03-01
影响因子：
6.3
通讯作者：
Macrae, IM
中科院分区：
文献类型：
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作者：
Carswell, HV;Bingham, D;Macrae, IM
我们先前报道，在动情前期(高内源性雌激素水平)，易卒中的自发性高血压大鼠(SHRSP)大脑中动脉闭塞(MCAO)后的脑损伤减轻，但正常血压的Wistar京都大鼠(WKY)没有。在本研究中，我们观察了外源性雌激素对SHRSP和WKY大鼠大脑中动脉阻塞后脑损伤的影响。将17β-雌二醇(0.025 mg或0.25 mg，21天释放)或与之匹配的安慰剂颗粒植入卵巢切除的WKY和SHRSP(3~4月龄)，2周后行远端透热诱导的MCAO。安慰剂组和17β-雌二醇组的血浆17β-雌二醇水平分别为：WKY 0.025 mg 16.4+/-8.5Pg/mL和25.85+/-12.6；WKY 0.25mg18.2+/-9.0和69.8+/-27.4；SHRSP0.25 mg20.7+/-8.8和81.0+/-16.9。在SHRSP中，安慰剂组和17β-雌二醇组的脑梗塞体积相似：SHRSP0.25 mg 126.7+/-22.3 mm(3)(n=8)和114.0 mg 113.5+/-22.3 mm(3)(n=8)(n=7)(n=7)(n=7)。在WKY组，0.025 mg剂量17β-雌二醇显著增加脑梗塞体积的65%[109.7+/-36.4 mm(3)(n=8)和59.7+/-19.3 mm(3)(n=8)(P=0.033，非配对t检验)]和0.025 mg剂量组[55.9+/-36.4 mm(3)(n=8)和0.025+/-6.7 mm(3)(n=4)]。因此，17β-雌二醇增加了正常血压大鼠的中风损害，而对中风倾向大鼠没有明显影响。尽管与我们的假设相反，但我们的发现增加了最近报道的17β-雌二醇在临床研究中的负面影响。
We previously reported that during pro-estrus (high endogenous estrogen levels), brain damage after middle cerebral artery occlusion (MCAO) was reduced in stroke-prone spontaneously hypertensive rats (SHRSP) but not in normotensive Wistar Kyoto rat (WKY). In the present study, we examined the effect of exogenous estrogen on brain damage after MCAO in SHRSP and WKY. A 17beta-estradiol (0.025mg or 0.25mg, 21 day release) or matching placebo pellet was implanted into ovariectomized WKY and SHRSP (3 to 4 months old) who then underwent distal diathermy-induced MCAO 2 weeks later. Plasma 17beta-estradiol levels for placebo and 17beta-estradiol groups were as follows: WKY 0.025 mg 16.4 +/- 8.5 (pg/mL, mean +/- SD) and 25.85 +/- 12.6; WKY 0.25 mg 18.2 +/- 9.0 and 69.8 +/- 27.4; SHRSP 0.25 mg 20.7 +/- 8.8 and 81.0 +/- 16.9. In SHRSP, infarct volumes at 24 hours after MCAO were similar in placebo and 17beta-estradiol groups: SHRSP 0.025 mg 126.7 +/- 15.3 mm(3) (n = 6) and 114.0 +/- 14.1 mm(3) (n = 8) (not significant); SHRSP 0.25 mg 113.5 +/- 22.3 mm(3) (n = 8) and 129.7 +/- 26.2 mm(3) (n = 7) (not significant), respectively. In WKY, 17beta-estradiol significantly increased infarct volume by 65% with 0.025mg dose [36.1 +/- 20.7 mm(3) (n = 8) and 59.7 +/- 19.3 mm(3) (n = 8) (P = 0.033, unpaired t-test)] and by 96% with 0.25 mg dose [55.9 +/- 36.4 mm(3) (n = 8) and 109.7 +/- 6.7 mm(3) (n = 4) (P = 0.017)]. Thus, 17beta-estradiol increased stroke damage in normotensive rats with no significant effect in stroke-prone rats. Despite being contrary to our hypothesis, our findings add substance to the recently reported negative effects of 17beta-estradiol in clinical studies.