Nephrology Department of The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China, No. 4, North Section 4, Second Ring Road, Chengdu 610057, China.
Physical Examination Center of General Hospital of Western Warzone, China, No. 270 Tianhui Road, Rongdu Avenue, Chengdu, Sichuan Province 610083, China.
J Radiat Res. 2023 Sep 22;64(5):769-782. doi: 10.1093/jrr/rrad050.
Radiation nephropathy refers to kidney damage caused by radiation therapy for malignant tumours. Currently, the pathogenesis is unclear and there is a lack of effective treatment methods. With the development of traditional Chinese medicine, the role of traditional Chinese medicine in the protection of radiation nephropathy is receiving increasing attention. Therefore, in this study, we used X-ray intraperitoneal irradiation to construct a mouse model of radiation nephropathy and studied the protective effect of traditional Chinese medicine Keluoxin on radiation nephropathy. We first analysed the potential targets and pathways of Keluoxin in the treatment of radiation nephropathy using network pharmacology methods, combined with in vitro and in vivo experimental verification, to study its potential mechanism. By searching the database, 136 components of Keluoxin were identified. A total of 333 intersectional targets related to radiation nephropathy were obtained. Among them, key targets include IL-6, TNF-α, HIF-1α, STAT1, STAT3, JAK1, JAK2, etc. In in vivo and in vitro experiments, we found that as the irradiation dose increased and time prolonged, kidney damage in mice gradually worsened in a time-dependent and dose-dependent manner. As the irradiation dose increases, the expression of pro-inflammatory factors Il-6, TNF-α, TGF-β increased. Compared with the irradiation group, the intervention of Keluoxin can reduce kidney damage caused by X-ray irradiation and reduce the expression of IL-6, TNF-α, TGF-β, STAT1, STAT3, JAK1, JAK2, etc. These results indicated that Keluoxin can alleviate kidney damage caused by X-ray irradiation, possibly by regulating the JAK/STAT signalling pathway, reducing inflammation levels and oxidative stress damage.
放射性肾病是指恶性肿瘤放射治疗引起的肾脏损害。目前，其发病机制尚不清楚，缺乏有效的治疗方法。随着中医药的发展，中医药在放射性肾病防治中的作用越来越受到重视。因此，本研究采用 X 射线腹腔内照射构建小鼠放射性肾病模型，研究中药克瘤心对放射性肾病的保护作用。我们首先采用网络药理学方法分析克瘤心治疗放射性肾病的潜在靶点和通路，结合体外和体内实验验证，研究其潜在机制。通过数据库检索，鉴定出克瘤心的 136 个成分。共获得与放射性肾病相关的 333 个交集靶点。其中关键靶点包括 IL-6、TNF-α、HIF-1α、STAT1、STAT3、JAK1、JAK2 等。在体内和体外实验中，我们发现随着照射剂量的增加和时间的延长，小鼠的肾脏损伤逐渐加重，呈时间依赖性和剂量依赖性。随着照射剂量的增加，促炎因子 Il-6、TNF-α、TGF-β 的表达增加。与照射组相比，克瘤心的干预可以减轻 X 射线照射引起的肾脏损伤，降低 IL-6、TNF-α、TGF-β、STAT1、STAT3、JAK1、JAK2 等的表达。这些结果表明，克瘤心可以减轻 X 射线照射引起的肾脏损伤，可能通过调节 JAK/STAT 信号通路，降低炎症水平和氧化应激损伤。
