HO1 and Wnt expression is independently regulated in female mice brains following permanent ischemic brain injury.
HO1 and Wnt expression is independently regulated in female mice brains following permanent ischemic brain injury.
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DOI：
10.1016/j.brainres.2017.02.006
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发表时间：
2017-05-01
期刊：
影响因子：
2.9
通讯作者：
Shah ZA
中科院分区：
文献类型：
--
作者：
Tulsulkar J;Ward A;Shah ZA
在整个流行病学研究、病理生理学、治疗和结果中观察到卒中的性别差异。在永久性脑缺血后，我们研究了血红素加氧酶(HO)的神经保护作用，该酶能将游离的血红素分解成胆红素、一氧化碳和胆绿素。我们已经在雄性小鼠中报道了HO1基因缺失会加剧永久性脑缺血后的脑损伤，其神经保护机制依赖于HO1/Wnt通路；然而，HO1/Wnt介导的神经保护在雌性小鼠脑中的作用仍有待研究。将卵巢完整的雌性小鼠、HO1−/−完整的雌性小鼠、HO1抑制剂锡中卟啉处理的雌性小鼠和/或去卵巢的雌性小鼠造成永久性缺血，7天后处死。与赋形剂处理组相比，SNMP处理7d后HO1酶活性显著降低。脑梗塞体积分析显示，与去卵巢组相比，完整组、HO1SNMP组和−/−治疗组的梗死灶明显减少，提示雌激素在神经保护中的作用。然而，在完整组、HO1SNMP组和−/−处理组之间观察到的脑梗塞体积没有差异，提示HO1神经保护的性别二型性作用。Western印迹分析表明，完整组和SNMP处理组在pMCAO后Wnt的表达没有显著差异。综上所述，这些结果表明，HO1神经保护是性二态的，Wnt的表达在永久性脑缺血后的女性大脑中受到独立调节。
A gender difference in stroke is observed throughout epidemiologic studies, pathophysiology, treatment and outcomes. We investigated the neuroprotective role of hemeoxygenase (HO) enzyme, which catabolizes free heme to bilirubin, carbon monoxide and biliverdin in the female brain after permanent ischemia. We have previously reported in male mice that genetic deletion of HO1 exacerbates the brain damage after permanent ischemia, and the mechanism of neuroprotection is dependent on the HO1/Wnt pathway; however, the role of HO1/Wnt mediated neuroprotection in the female brain is yet to be investigated. We subjected ovary intact female mice, HO1−/− intact, HO1 inhibitor tin mesoporphyrin (SnMP) treated intact and/or ovariectomized female mice to permanent ischemia (pMCAO), and the animals were sacrificed after 7 days. The SnMP treatment for 7 days significantly reduced the HO1 enzyme activity as compared to that of vehicle treated group. Infarct volume analysis showed significantly lower infarct in intact, HO1−/− intact, and SnMP treated group as compared to the OVX group, suggesting the role of estrogen in neuroprotection. However, there were no differences in infarct volume observed between the intact, HO1−/− and SnMP treated group, suggesting a sexually dimorphic role of HO1 neuroprotection. Western blot analysis on intact and SnMP-treated groups subjected to pMCAO suggested no significant differences in Wnt expression. Together, these results suggest that HO1 neuroprotection is sexually dimorphic and Wnt expression is independently regulated in the female brain following permanent ischemia.