Wang Chi, Yan Muyang, Jiang Hui, Wang Qi, Guan Xu, Chen Jingwen, Wang Chengbin
Department of Clinical Laboratory, PLA General Hospital, 100853 Beijing, People's Republic of China.
Department of Hyperbaric Chamber, PLA General Hospital, 100853 Beijing, People's Republic of China.
Int Immunopharmacol. 2016 Nov;40:300-309. doi: 10.1016/j.intimp.2016.09.010. Epub 2016 Sep 16.
Hypobaric hypoxia, frequently encountered at high altitude, may lead to lung and cerebrum injury. Our study aimed to investigate whether puerarin could exert ameliorative effects on rats exposed to hypobaric hypoxia via regulation of aquaporin (AQP) and NF-κB signaling pathway in lung and cerebrum.
40 Sprague Dawley rats were divided into four groups (normal control group, hypobaric hypoxia group, puerarin group and dexamethasone group). Wet/dry ratio, blood gas, pathological changes of lung and cerebrum and spatial memory were observed in each group. Inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined with ELISA and expression of AQP1, AQP4, NF-κB signaling pathway in lung and cerebrum with western blot RESULTS: Puerarin showed significant preventative effects on tissue injury and behavioral changes, as evidenced by histopathological findings and Morris water maze. In addition, levels of inflammatory cytokines in BALF decreased in the two preventative groups compared with those of hypobaric hypoxia group. AQP in lung and cerebrum increased under the condition of hypobaric hypoxia while was down regulated in both two preventative groups. NF-κB and IκB was also inhibited by puerarin.
Our study suggested that lung and cerebrum injury, increased inflammatory cytokines in BALF and increased AQP1, AQP4 and NF-κB signaling pathway occurred under the condition of hypobaric hypoxia. Moreover, puerarin could prevent lung and cerebrum injury of rats exposed to hypobaric hypoxia via down-regulation of inflammatory cytokines, AQP1 and AQP4 expression and NF-κB signaling pathway.
高原地区常见的低压低氧环境可能导致肺和脑损伤。本研究旨在探讨葛根素是否能通过调节肺和脑中水通道蛋白(AQP)及核因子κB(NF-κB)信号通路,对低压低氧环境下的大鼠发挥改善作用。
将40只Sprague Dawley大鼠分为四组(正常对照组、低压低氧组、葛根素组和地塞米松组)。观察每组大鼠的肺和脑湿干比、血气、病理变化及空间记忆。采用酶联免疫吸附测定法(ELISA)检测支气管肺泡灌洗液(BALF)中的炎性细胞因子,并用蛋白质印迹法检测肺和脑中AQP1、AQP4及NF-κB信号通路的表达。
组织病理学检查结果和莫里斯水迷宫实验均表明,葛根素对组织损伤和行为变化具有显著的预防作用。此外,与低压低氧组相比,两个预防组BALF中炎性细胞因子水平降低。低压低氧条件下肺和脑中AQP增加,而两个预防组中AQP均下调。葛根素还可抑制NF-κB和IκB。
本研究表明,低压低氧环境下会出现肺和脑损伤、BALF中炎性细胞因子增加以及AQP1、AQP4和NF-κB信号通路增强。此外,葛根素可通过下调炎性细胞因子、AQP1和AQP4表达以及NF-κB信号通路,预防低压低氧环境下大鼠的肺和脑损伤。