摘要
目的探讨负载吲哚-3-甲醛的菊粉水凝胶对放射性肠损伤的防治作用和机制。方法使用流变仪检测负载吲哚-3-甲醛的菊粉水凝胶的成胶性能和可注射性。利用CCK-8实验检测负载吲哚-3-甲醛的菊粉水凝胶的生物相容性。将18只6~8周龄的雄性C57BL/6小鼠按照体重分层随机分为空白对照组、单纯照射组和照射+水凝胶防护组,每组6只。采用137Csγ射线照射腹部,照射剂量为17 Gy。照射前2 d和照射后的2~3 d分别给予200μl/d的负载吲哚-3-甲醛的菊粉水凝胶,同时给予单纯照射组等量的无菌水灌胃。照射后4 d处死小鼠并分离肠道组织,根据苏木精-伊红(HE)染色、Ki67免疫组织化学法和TUNEL免疫荧光染色,分析小鼠肠道组织的损伤情况、肠上皮细胞辐射后的增殖及凋亡情况。采用qRT-PCR检测炎性因子和抗氧化因子mRNA的表达水平。通过16S rRNA测序分析小鼠肠道菌群的变化。结果流变仪的测试结果显示菊粉水凝胶成功制备。CCK-8实验结果显示所制备的菊粉水凝胶有良好的生物相容性。与单纯照射组相比较,照射+水凝胶防护组的小鼠肠道组织在辐射后病理结构未见明显紊乱和破坏,肠道细胞增殖活性显著增强,较照射组提高约1.5倍(t=8.35,P<0.05)。同时,辐射引起的细胞凋亡水平明显降低(t=7.94,P<0.05)。与单纯照射组相比,照射+水凝胶防护组的抗炎因子白介素10(IL-10)和抗氧化因子核因子E2相关因子2(NRF-2)、血红素加氧酶-1(HO-1)的表达水平升高,差异有统计学意义(t=3.16、24.83、5.92,P<0.05)。照射+水凝胶防护组的白介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)等促炎因子的水平较单纯照射组降低,差异有统计学意义(t=5.15、3.82、3.83,P<0.05)。结论负载吲哚-3-甲醛的菊粉水凝胶能够有效促进肠道细胞的增殖,显著降低辐射引起的细胞凋亡,提升抗炎和抗氧化因子的表达水平,并调节肠道菌群的组成和丰度,从而有效防护放射性肠损伤。
Objective To explore the protective effects and mechanisms of an indole-3-acetaldehyde(I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury.Methods The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer,and its biocompatibility was assessed via a CCK-8 assay.Eighteen C57BL/6 mice(aged:6-8 weeks)were stratified by body weight and randomly assigned into three groups with 6 mice in each group:blank control,irradiation-only,and irradiation+hydrogel protection.Abdominal irradiation was administered using 137Csγ-rays at 17 Gy.The irradiation+hydrogel protection group received 200μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation.Meanwhile,the irradiation-only group was treated with an equivalent volume of sterile water via gavage.The mice were euthanized four days post-irradiation,and their intestinal tissues were harvested.Hematoxylin-eosin(HE)staining,Ki67 immunohistochemistry,and TUNEL immunofluorescence were performed to assess histopathological damage,epithelial cell proliferation,and apoptosis,respectively.Quantitative real-time PCR(qRT-PCR)was employed to measure mRNA levels of inflammatory and antioxidant factors.Gut microbiota composition was analyzed via 16S rRNA sequencing.Results The test results of the rheometer confirmed successful hydrogel formation.CCK-8 assays demonstrated excellent biocompatibility.Compared with the irradiation-only group,the irradiation+hydrogel protection group exhibited preserved intestinal histoarchitecture,a 1.5-fold increase in intestinal cell proliferation(t=8.35,P<0.05),and a 2-fold reduction in radiation-induced apoptosis(t=7.94,P<0.05).Moreover,the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1(t=3.16,24.83,5.92,P<0.05),alongside reduced levels of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α(t=5.15,3.82,3.83,P<0.05).Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group.Conclusions The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation,reduce radiation-induced apoptosis,and enhance both anti-inflammatory and antioxidant responses.In addition,it regulates gut microbiota composition and abundance,protecting against radiation-induced intestinal injury.
作者
李拓
马菲菲
管杰冰
谢思宇
王宁
何宁宁
宋会娟
李建国
刘强
Li Tuo;Ma Feifei;Guan Jiebing;Xie Siyu;Wang Ning;He Ningning;Song Huijuan;Li Jianguo;Liu Qiang(School of Basic Medical Sciences,Shandong Second Medical University,Weifang 261000,China;TianjinKey Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Sciences,Tianjin 300192,China)
出处
《中华放射医学与防护杂志》
北大核心
2025年第5期408-415,共8页
Chinese Journal of Radiological Medicine and Protection
基金
国家自然科学基金(82001954,32071241,32171239)
辐射防护实验室开放基金(CIRP-DTRI20220202)。
关键词
放射性肠损伤
菊粉水凝胶
吲哚-3-甲醛
肠道菌群
Radiation-induced intestinal injury
Inulin-based hydrogel
Indole-3-aldehyde
Intestinal microbiota
