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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro
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Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro

机译:糖尿病相关性差异在体内缺血和体外人脑内皮细胞中的脑内内皮素系统

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摘要

The endothelin (ET) system has been implicated to contribute to the pathophysiology of cognitive impairment and stroke in experimental diabetes. Our goals were to test the hypotheses that (1) circulating and (or) periinfarct ET-1 levels are elevated after stroke in both sexes and this increase is greater in diabetes, (2) ET receptors are differentially regulated in the diabetic brain, (3) brain microvascular endothelial cells (BMVEC) of female and male origin express the ETA receptor subtype, and (4) diabetes- and stroke-mimicking conditions increase ET-1 levels in BMVECs of both sexes. Control and diabetic rats were randomized to sham or stroke surgery. BMVECs of male (hBEC5i) and female (hCMEC/D3) origin, cultured under normal and diabetes-mimicking conditions, were exposed to normoxia or hypoxia. Circulating ET-1 levels were higher in diabetic animals and this was more pronounced in the male cohort. Stroke did not further increase plasma ET-1. Tissue ET-1 levels were increased after stroke only in males, whereas periinfarct ET-1 increased in both control and diabetic females. Male BMVECs secreted more ET-1 than female cells and hypoxia increased ET-1 levels in both cell types. There was sexually dimorphic regulation of ET receptors in both tissue and cell culture samples. There are sex differences in the stroke- and diabetes-mediated changes in the brain ET system at the endothelial and tissue levels.
机译:内皮素(ET)系统参与了实验性糖尿病认知障碍和中风的病理生理学。我们的目标是检验以下假设:(1)男女中风后循环和(或)梗死周围ET-1水平升高,糖尿病患者的增加更大,(2)ET受体在糖尿病患者大脑中受到差异调节,(3)女性和男性来源的脑微血管内皮细胞(BMVEC)表达ETA受体亚型,(4)糖尿病和类似中风的情况会增加男女BMVEC中的ET-1水平。对照组和糖尿病大鼠被随机分为假手术组和中风手术组。在正常和模拟糖尿病条件下培养的雄性(hBEC5i)和雌性(hCMEC/D3)来源的BMVEC暴露于常氧或缺氧。糖尿病动物的循环ET-1水平较高,而男性队列中的情况更为明显。中风并没有进一步增加血浆ET-1。只有男性中风后组织ET-1水平升高,而对照组和糖尿病女性梗死周围ET-1水平均升高。雄性BMVEC比雌性细胞分泌更多的ET-1,缺氧增加了这两种细胞的ET-1水平。在组织和细胞培养样本中,ET受体都存在性二型调节。在脑血管内皮和组织水平上,中风和糖尿病介导的脑ET系统变化存在性别差异。

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