目的 探討冬蟲夏草治療急性放射性直腸炎的療效及可能的作用機制。方法 將25只小鼠隨機分為5組：對照組、模型組和冬蟲夏草低、中、高劑量（0.25、0.50、1.00 g·kg^-1）組，每組5只，除對照組外的4組小鼠予直線加速器6-MV的X射線行下腹部照射，總劑量12 Gy，建立急性放射性直腸炎模型。照射后次日開始ig給藥，觀察并記錄各組小鼠狀態(tài)、體質(zhì)量變化情況；HE染色觀察各組小鼠腸道組織病理學(xué)改變；ELISA法檢測各組小鼠血清丙二醛（MDA）、超氧化物歧化酶（SOD）、Fe²⁺以及炎癥因子白細胞介素-6 （IL-6）、白細胞介素-1β （IL-1β）、腫瘤壞死因子-α （TNF-α）水平； Western blotting檢測各組小鼠直腸組織中中鐵死亡相關(guān)蛋白：長鏈酯酰輔酶A合成酶（ACSL4）、溶質(zhì)載體家族7成員11（SLC7A11）、谷胱甘肽過氧化物酶4（GPX4）表達水平；透射電鏡觀察各組小鼠直腸細胞中線粒體數(shù)量及形態(tài)結(jié)構(gòu)的變化情況。結(jié)果 與對照組相比，模型組小鼠精神萎靡，體質(zhì)量下降，部分小鼠有肛門出血的癥狀；與模型組比較，冬蟲夏草組小鼠癥狀普遍緩解。HE染色結(jié)果顯示模型組腸道上皮細胞壞死脫落，黏膜層出現(xiàn)不同程度地出血水腫；用藥后，腸道黏膜有所恢復(fù)，病變程度明顯好轉(zhuǎn)。ELISA結(jié)果顯示，與對照組相比，模型組炎癥因子TNF-α、IL-6、IL-1β、MDA、Fe²⁺水平顯著升高（P<0.001），SOD水平顯著下降（P<0.001）；治療后，與模型組相比，冬蟲夏草中、高劑量組TNF-α、IL-6、IL-1β、MDA、Fe²⁺含量顯著下降，SOD含量顯著增高（P<0.001）。Western blotting實驗結(jié)果顯示，與對照組比較，模型組ACSL4蛋白表達水平顯著升高（P<0.05），SLC7A11及GPX4蛋白表達水平顯著降低（P<0.05）；與模型組比較，冬蟲夏草中、高劑量組ACSL4蛋白的表達水平顯著降低（P<0.05），同時SLC7A11、GPX4蛋白表達水平顯著升高。透射電鏡結(jié)果發(fā)現(xiàn)，模型組線粒體數(shù)量下降，體積變小，膜密度增加，嵴減少；冬蟲夏草治療后各組線粒體結(jié)構(gòu)損傷程度較模型組有所緩解。結(jié)論 冬蟲夏草能緩解放射性直腸炎，作用機制可能與調(diào)控SLC7A11、GPX4、ACSL4蛋白的表達，同時抑制炎癥因子，增加機體的抗鐵死亡能力相關(guān)。

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.

R285.5

國家自然科學(xué)基金資助項目（81860534）；內(nèi)蒙古自治區(qū)科技計劃項目（2019GG039/086，2021GG0167）；內(nèi)蒙古自然科學(xué)基金資助項目（2021MS08152/8154）；內(nèi)蒙古自治區(qū)高等學(xué)校青年科技英才支持計劃項目（NJYT22004）；內(nèi)蒙古自治區(qū)衛(wèi)生健康科技計劃項目（202201356）；內(nèi)蒙古醫(yī)科大學(xué)青年創(chuàng)新基金項目（YKD2020QNCX057）