Li Yangyang, Zhang Liying, Zhang Yiming, Miao Zhiming, Liu Zhiwei, Zhou Gucheng, He Jinpeng, Ding Nan, Zhou Heng, Zhou Ting, Niu Fan, Li Jing, Liu Yongqi
Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Lanzhou, China.
Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Lanzhou, China; Gansu Institute of Cardiovascular Diseases, Lanzhou, China.
Phytomedicine. 2022 Dec;107:154445. doi: 10.1016/j.phymed.2022.154445. Epub 2022 Sep 9.
Guiqi Baizhu Decoction (GQBZD) has a good protective effect on radiation-induced intestinal edema (RIIE). However, the underlying molecular mechanisms need further elucidation.
To reveal the potential mechanism of RIIE and GQBZD treatment.
SD rats were irradiated with 6Gy X-ray to establish RIIE model. The general condition of the rats was observed; the dry/wet weight ratio of colon tissue was detected; the morphological changes of colon tissue were observed by HE staining; the expressions of ROS, HIF-1α and AQP4 in colon tissue were detected by confocal laser scanning; the expression of edema-related proteins was detected by Western blot. In addition, human colon epithelial cells (NCM460) was irradiated with 2Gy X-ray, and HIF-1α expression in NCM460 was knocked down by small interfering RNA (siRNA) transfection, and the activity of Na/K-ATPase was detected by enzyme activity kit; the ROS expression was detected by flow cytometer; the AQP4 expression was detected by laser confocal microscopy; and the expression of edema-related proteins were detected by Western blot.
We found that after irradiation, the colon tissue of rats was significantly edema, mainly manifested as mucosal and submucosal edema, and the ultrastructure was reflected in the structural damage of nucleus and mitochondria. ROS, HIF-1α and AQP4 were significantly expressed, and Na/K-ATPase expression/activity was decreased. After the intervention of GQBZD, the edema of the colon tissue of the rats was improved, the expressions of ROS, HIF-1α and AQP4 were decreased, and the expression/activity of Na/K-ATPase was increased.
Ionizing radiation (IR) can cause significant intestinal edema. AQP4 and Na/K-ATPase are the key factors of RIIE, which are regulated by ROS and HIF-1α. GQBZD can improve hypoxia and oxidative stress, regulate the expression of AQP4 and Na/K-ATPase, and achieve a protective effect on RIIE. This study is the first to reveal the mechanism of RIIE.
归芪白术汤（GQBZD）对辐射诱导的肠道水肿（RIIE）具有良好的保护作用。然而，其潜在的分子机制尚需进一步阐明。
揭示RIIE及GQBZD治疗的潜在机制。
用6Gy X射线照射SD大鼠以建立RIIE模型。观察大鼠的一般情况；检测结肠组织的干/湿重比；通过苏木精-伊红（HE）染色观察结肠组织的形态变化；用共聚焦激光扫描检测结肠组织中活性氧（ROS）、缺氧诱导因子-1α（HIF-1α）和水通道蛋白4（AQP4）的表达；用蛋白质免疫印迹法检测水肿相关蛋白的表达。此外，用2Gy X射线照射人结肠上皮细胞（NCM460），通过小干扰RNA（siRNA）转染敲低NCM460中HIF-1α的表达，用酶活性试剂盒检测钠钾ATP酶（Na/K-ATPase）的活性；用流式细胞仪检测ROS的表达；用激光共聚焦显微镜检测AQP4的表达；用蛋白质免疫印迹法检测水肿相关蛋白的表达。
我们发现照射后大鼠结肠组织明显水肿，主要表现为黏膜和黏膜下水肿，超微结构表现为细胞核和线粒体的结构损伤。ROS、HIF-1α和AQP4表达显著增加，Na/K-ATPase表达/活性降低。GQBZD干预后，大鼠结肠组织水肿改善，ROS、HIF-1α和AQP4表达降低，Na/K-ATPase表达/活性增加。
电离辐射（IR）可导致明显的肠道水肿。AQP4和Na/K-ATPase是RIIE的关键因素，受ROS和HIF-1α调节。GQBZD可改善缺氧和氧化应激，调节AQP4和Na/K-ATPase的表达，对RIIE起到保护作用。本研究首次揭示了RIIE的机制。
