Sheng Lei, Hu Fan, Yu Hanqing, Tao Xueyou, Jia Rumeng, Gu Yufeng, Chen Lu, Kong Hong, Miao Chen, Fei Wenjing, Yang Yang, Jia Jinhui, Zhu Xia, He Xueming, Hu Liang, Ma Jianxin, Liu Wen-Tao, Yang Mi
The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Front Pharmacol. 2022 Mar 14;13:743708. doi: 10.3389/fphar.2022.743708. eCollection 2022.
Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous "inflammation brake." We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor and . Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.
放射性肠炎是放射治疗的主要不良反应之一，其病因尚不明确，治疗选择有限。肠道炎症和缺血是放射性肠炎的核心机制。细胞因子信号转导抑制因子3（SOCS3）是一种内源性的“炎症刹车”。我们假设芍药苷（一种蒎烷单萜苦味糖苷）可以增加SOCS3的表达，以减轻炎症和缺血，并改善小鼠的肠炎。采用激光多普勒血流仪检测肠道血流变化。利用RAW264.7细胞和人脐静脉内皮细胞研究芍药苷的作用机制。结果发现，辐射导致小鼠死亡率高、肠道炎症反应和低血流量。芍药苷有效减轻肠道萎缩，预防血栓形成，改善放射性肠炎，并降低接受放疗小鼠的死亡率。此外，芍药苷增加生长停滞特异性基因6（Gas6）的释放和Axl受体的磷酸化，随后诱导SOCS3的表达，并抑制凋亡信号调节激酶1和组织因子的表达。基于我们的研究结果，我们认为芍药苷可能通过激活Gas6/Axl/SOCS3轴，进而减轻肠道炎症和缺血，对缓解放射性肠炎有效。
