首页> 外文期刊>Journal of neuroinflammation >Curcumin prophylaxis mitigates the incidence of hypobaric hypoxia-induced altered ion channels expression and impaired tight junction proteins integrity in rat brain
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Curcumin prophylaxis mitigates the incidence of hypobaric hypoxia-induced altered ion channels expression and impaired tight junction proteins integrity in rat brain

机译:姜黄素预防可减轻低压缺氧引起的大鼠脑离子通道表达改变和紧密连接蛋白完整性受损的发生

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Background The present study was proposed to elucidate the prophylactic role of curcumin in the prevention of hypoxia-induced cerebral edema (HACE). Methods Rats were exposed to simulated hypobaric hypoxia at 7620 m for 24 h at 25?±?1 °C. Transvascular leakage, expression of transcriptional factors (nuclear factor-kappa B (NF-κB) and hypoxia inducible factor 1 alpha (Hif-1α) and also the genes regulated by these transcriptional factors, sodium potassium-adenosine triphosphatase (Na+/K+-ATPase) and endothelial sodium channel (ENaC) levels and brain tight junction (TJ) proteins like ZO-1, junctional adhesion molecule C (JAMC), claudin 4 and claudin 5 levels were determined in the brain of rats under hypoxia by Western blotting, electro mobility shift assay, ELISA, immunohistochemistry, and histopathology along with haematological parameters. Simultaneously, to rule out the fact that inflammation causes impaired Na+/K+-ATPase and ENaC functions and disturbing the TJ integrity leading to cerebral edema, the rats were pre-treated with curcumin (100 mg/kg body weight) 1 h prior to 24-h hypoxia. Results Curcumin administration to rats, under hypoxia showed a significant decrease (p?
机译:背景技术本研究旨在阐明姜黄素在预防缺氧性脑水肿(HACE)中的预防作用。方法大鼠在25?±?1°C下于7620 m暴露于模拟的低压缺氧24小时。跨血管渗漏,转录因子(核因子-κB(NF-κB)和缺氧诱导因子1α(Hif-1α)的表达,以及受这些转录因子调控的基因,钾钠-腺苷三磷酸钠(Na + / K + -ATPase)缺氧条件下,通过Western印迹,电法测定了大鼠大脑中的内皮钠通道(ENaC)水平和ZO-1,连接粘附分子C(JAMC),claudin 4和claudin 5水平的脑紧密连接(TJ)蛋白同时,为了排除炎症导致Na + / K + -ATPase和ENaC功能受损并破坏TJ完整性导致脑水肿的事实,采用了迁移率变动分析,ELISA,免疫组化和组织病理学以及血液学参数。在缺氧24小时前1小时服用姜黄素(100 mg / kg体重)结果姜黄素在缺氧条件下对大鼠的给药显示脑含水量显着降低(p <0.001)(3.53±0.58)。与对照组(24小时缺氧)相比,大鼠脑部的干湿重(W / D)比和跨血管渗漏(136.2?±?13.24相对荧光单位/克(rfu / g)) λ±1.0W / D比和262.42±±24.67rfu / g。姜黄素的预防显着减弱了NF-κB的上调(p <0.001),从而导致促炎性细胞因子水平的下调(↓IL-1,IL-2,IL-18和TNF-α),细胞粘附分子(↓P-选择素和E-选择素)和增加的抗炎细胞因子(↑IL-10)。姜黄素稳定脑HIF-1α水平,然后在缺氧条件下维持VEGF水平以及Na + / K + -ATPase和ENaC水平上调(p <0.001)。姜黄素在缺氧下恢复了大脑的ZO-1,JAMC,claudin 4和claudin 5水平(p <0.001)(p <0.001)。组织病理学观察显示,补充姜黄素的大鼠脑内没有水肿和炎症。结论这些结果表明姜黄素是一种改善HACE的有效药物,因为它通过维持低氧状态下大鼠脑中紧密连接蛋白的完整性和增加离子通道的表达来有效减轻炎症和体液流入。

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