NADH protect against radiation enteritis by enhancing autophagy and inhibiting inflammation through PI3K/AKT pathway.
NADH protect against radiation enteritis by enhancing autophagy and inhibiting inflammation through PI3K/AKT pathway.
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DOI：
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发表时间：
2018
影响因子：
2.2
通讯作者：
Jinting Wang;Wenxi Xie;Faquan Liu;Y. Bi;Xiongjie Zhu;Qi-En Wang;Yan-Fang Zheng
中科院分区：
文献类型：
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作者：
Jinting Wang;Wenxi Xie;Faquan Liu;Y. Bi;Xiongjie Zhu;Qi-En Wang;Yan-Fang Zheng
放射治疗是治疗癌症的重要手段，但大剂量放射治疗有严重的副作用。放射治疗中最大的挑战之一是辐射既影响健康组织，也影响癌症组织。对于腹部或盆腔损伤，肠道最容易受到辐射损伤。辐射可引起放射性肠炎、肠炎性渗出或肠穿孔。辅酶NADH参与核酸、蛋白质和碳水化合物的能量代谢和运输。在我们的研究中，NADH被用来保护IEC-6正常肠上皮细胞的肠壁免受辐射损伤。通过流式细胞仪检测发现，NADH能抑制细胞死亡和ROS的产生。免疫荧光检测显示NADH组细胞自噬增加。免疫印迹结果显示，NADH促进微管相关蛋白1A/1B-轻链3(Lc3)-I向Lc3-II转化，IL-1β和肿瘤坏死因子α的表达呈剂量依赖性下降。有趣的是，一种特异性的PI3K/AKT抑制剂(3MA)减少了炎症因子的表达。在动物实验中，12Gy射线照射后，RT+NADH组的肿瘤坏死因子α低于RT组，而LC_(33)II高于RT组。与模型组相比，NADH组无明显损伤。因此，我们的研究提供了证据，NADH可能通过PI3K/AKT途径抑制正常肠道细胞的炎症和促进自噬，从而对放射性肠炎具有保护作用。
Radiotherapy is an important method for cancer treatment but it has serious side-effects at high doses. One of the greatest challenges in radiotherapy is that radiation affects both healthy tissue and cancer tissues. For abdominal or pelvic lesions, the bowel is the most easily injured by irradiation. Radiation may cause radiation enteritis, intestinal inflammatory infiltration, or intestinal perforation. Coenzyme NADH involves in energy metabolism and transportation of nucleic acid, proteins and carbohydrates. In our study, NADH was used to protect the intestinal wall from irradiation injury in IEC-6 normal intestinal epithelial cells. By flow cytometry, we found that NADH can inhibit the cell death and the producing of reactive oxygen species (ROS). The immunofluorescence assay showed that cell autophagy was increased in the NADH group. Western blot data indicated that NADH promoted the microtubule associated protein 1A/1B-light chain 3(LC3)-I to LC3II and the expression of IL-1β and TNFα decreased in a dose dependent manner. Interestingly, a specific PI3K/AKT inhibitor (3MA) decreased the expression of inflammatory factors. In the animal experiment, after 12 Gy radiation, there were less TNFα and more LC3II in the RT+NADH group than that of RT group. Compared with the mock, there was no significant damage in the NADH group. Thus, our study provides the evidence that NADH may protect against radiation enteritis by suppressing inflammation and enhancing autophagy through PI3K/AKT pathway in normal intestinal cells.