目的 探讨冬虫夏草治疗急性放射性直肠炎的疗效及可能的作用机制。方法 将25只小鼠随机分为5组：对照组、模型组和冬虫夏草低、中、高剂量（0.25、0.50、1.00 g·kg-1）组，每组5只，除对照组外的4组小鼠予直线加速器6-MV的X射线行下腹部照射，总剂量12 Gy，建立急性放射性直肠炎模型。照射后次日开始ig给药，观察并记录各组小鼠状态、体质量变化情况；HE染色观察各组小鼠肠道组织病理学改变；ELISA法检测各组小鼠血清丙二醛（MDA）、超氧化物歧化酶（SOD）、Fe2+以及炎症因子白细胞介素-6 （IL-6）、白细胞介素-1β （IL-1β）、肿瘤坏死因子-α （TNF-α）水平； Western blotting检测各组小鼠直肠组织中中铁死亡相关蛋白：长链酯酰辅酶A合成酶（ACSL4）、溶质载体家族7成员11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）表达水平；透射电镜观察各组小鼠直肠细胞中线粒体数量及形态结构的变化情况。结果 与对照组相比，模型组小鼠精神萎靡，体质量下降，部分小鼠有肛门出血的症状；与模型组比较，冬虫夏草组小鼠症状普遍缓解。HE染色结果显示模型组肠道上皮细胞坏死脱落，黏膜层出现不同程度地出血水肿；用药后，肠道黏膜有所恢复，病变程度明显好转。ELISA结果显示，与对照组相比，模型组炎症因子TNF-α、IL-6、IL-1β、MDA、Fe2+水平显著升高（P<0.001），SOD水平显著下降（P<0.001）；治疗后，与模型组相比，冬虫夏草中、高剂量组TNF-α、IL-6、IL-1β、MDA、Fe2+含量显著下降，SOD含量显著增高（P<0.001）。Western blotting实验结果显示，与对照组比较，模型组ACSL4蛋白表达水平显著升高（P<0.05），SLC7A11及GPX4蛋白表达水平显著降低（P<0.05）；与模型组比较，冬虫夏草中、高剂量组ACSL4蛋白的表达水平显著降低（P<0.05），同时SLC7A11、GPX4蛋白表达水平显著升高。透射电镜结果发现，模型组线粒体数量下降，体积变小，膜密度增加，嵴减少；冬虫夏草治疗后各组线粒体结构损伤程度较模型组有所缓解。结论 冬虫夏草能缓解放射性直肠炎，作用机制可能与调控SLC7A11、GPX4、ACSL4蛋白的表达，同时抑制炎症因子，增加机体的抗铁死亡能力相关。
Objective To investigate the efficacy and possible mechanism of Cordyceps sinensis in the treatment of radiation proctitis. Method Twenty-five mice were randomly divided into five groups: control group and model group with low, middle and high dose of Cordyceps sinensis (0.25, 0.50, and 1.00 g·kg-1), with five mice in each group. Four groups of mice except the control group were irradiated by linear accelerator 6-MV X-ray on the lower abdomen with a total dose of 12 Gy to establish the model of acute radiation proctitis. The changes of morphology and body weight of mice in each group were observed and recorded. The intestinal histopathological changes of mice in each group were observed by HE staining. The contents of serum malondialdehyde (MDA), superoxide dismutase (SOD), Fe2+ and inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Western blotting was used to detect the expression of iron death-related proteins: longchain ester acyl-CoA synthetase (ACSL4), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), and the changes of mitochondrial number and morphology were observed by transmission electron microscope. Results Compared with control group, the mice in the model group were dispirited, their body weight decreased, and some mice had symptoms of anal bleeding, compared with model group, the symptoms in the treatment group were generally relieved, and the results of HE staining showed that the intestinal epithelial cells were necrotic and exfoliated, and the mucosal layer showed bleeding and edema in varying degrees. After treatment, the intestinal mucosa recovered and the degree of lesion improved significantly. The results of ELISA detection showed that compared with control group, the contents of MDA, Fe2+ and inflammatory factors in the model group increased significantly (P< 0.001), while the content of SOD decreased significantly (P< 0.001). Compared with model group, the contents of MDA, Fe2+ and inflammatory factors in the middle and high treatment groups of Cordyceps sinensis decreased significantly (P< 0.05, 0.01), and the content of SOD increased significantly (P< 0.05, 0.01). The results of Western blotting experiment showed that compared with model group, the expression level of ACSL4 protein in the middle and high treatment groups of Cordyceps sinensis decreased significantly, while the expression levels of SLC7A11 and GPX4 protein in the Cordyceps sinensis group were significantly higher than those in the model group. The results of transmission electron microscope showed that in the model group, the number of mitochondria decreased, the volume became smaller, the membrane density increased and the crest decreased. After treatment, the structural damage of mitochondria in each group was alleviated compared with that in the model group. Conclusion Cordyceps sinensis can alleviate the intestinal injury and inflammation caused by radiotherapy, which may be through regulating the expression of SLC7A11, GPX4, ACSL4 proteins, inhibiting inflammatory factors, increasing the antiferroptosis ability of the body, and protecting the intestinal tract.