负载姜黄素-维生素E复合物的温敏水凝胶对放射性口腔黏膜炎小鼠的治疗效果分析  

Therapeutic effect of thermosensitive hydrogel containing curcumin-vitamin E complex on radiation-induced oral mucositis in mice

作　　者：段娟 李可 何睿 胡雯[1,2] DUAN Juan;LI Ke;HE Rui;HU Wen(West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China;Department of Clinical Nutrition,West China,Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China)

机构地区：[1]四川大学华西公共卫生学院/四川大学华西第四医院,成都610041 [2]四川大学华西医院临床营养科,成都610041

出　　处：《华西医学》2025年第1期60-67,共8页West China Medical Journal

基　　金：四川省自然科学基金(2023NSFSC1208)。

摘　　要：目的研究载有姜黄素-维生素E(vitamin E,VE)复合物的温敏水凝胶(以下简称“姜黄素-VE凝胶”)对放射所致小鼠口腔黏膜炎的治疗效果。方法以合成的姜黄素-VE复合物为载物,泊洛沙姆为基质,制备姜黄素-VE凝胶。采用傅里叶红外光谱仪表征姜黄素-VE复合物结构,通过扫描电镜测定姜黄素-VE凝胶微观结构,流变仪测定凝胶化温度,测定凝胶溶胀降解性并使用万能试验机测定凝胶黏附性。将30只无特定病原体级健康雄性BALB/C小鼠随机分为空白组、辐射组、辐射+凝胶组,每组各10只。辐射组、辐射+凝胶组通过单次大剂量辐射造模(25 Gy),空白组只麻醉不辐射。空白组及辐射组在辐射后1~7 d给予常规饲料及饮水,辐射+凝胶组在此基础上每日给予姜黄素-VE凝胶干预2次,辐射后第8天处死小鼠。记录辐射后各组小鼠体重变化情况;甲苯胺蓝染色测定舌组织表面溃疡面积;对小鼠舌组织进行病理观察;测定舌组织超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性及丙二醛水平;酶联免疫吸附试验测定舌组织肿瘤坏死因子α、白细胞介素(interleukin,IL)-1β、IL-6的水平;免疫组织化学法测定磷酸化组蛋白H2AX、核转录因子红系2相关因子2的分布及阳性表达量。结果姜黄素-VE凝胶内部为多孔网状结构,凝胶化温度为30℃,溶胀率接近300%,48 h后凝胶降解率超过95%,黏附强度为12.748 kPa。体内实验结果表明,与辐射组比较,辐射+凝胶组小鼠体重上升(P<0.05),溃疡面积显著减少(P<0.05),过氧化氢酶活性增加(P<0.05),肿瘤坏死因子α、IL-1β及IL-6水平下降(P<0.05),磷酸化组蛋白H2AX表达下调(P<0.05)。结论姜黄素-VE凝胶可通过减少辐射引起的DNA损伤、抑制活性氧产生以及有效降低小鼠舌组织炎症水平来延缓或减弱放射性口腔黏膜炎的进程。Objective To observe the therapeutic effect of thermosensitive hydrogel containing curcumin vitamin E(VE)complex(hereinafter referred to as“curcumin-VE hydrogel”)on radiation-induced oral mucositis in mice.Methods Curcumin-VE hydrogel was prepared using the synthesized curcumin-VE complex as the carrier and poloxam as the substrate.The structure of curcumin-VE complex was characterized by Fourier transform infrared spectrometer,the microstructure of curcumin-VE hydrogel was determined by scanning electron microscope,and the gelation temperature was determined by rheometer,gel swelling and degradation were tested and gel adhesion was determined using a universal testing machine.Thirty healthy male BALB/C mice with specific pathogen free grade were randomly divided into three groups,with ten mice in each group.The radiation group and radiation+hydrogel group were modeled by a single high dose of radiation(25 Gy),while the control group had anesthesia but no radiation.The control group and radiation group were given daily feed and water 7 days after radiation.In addition to daily feed and water,the radiation+hydrogel group was given curcumin-VE hydrogel twice a day.The mice were sacreficed on the 8th day after radiation.The weight changes of each group were recorded after radiation.The ulceration area of tongue was measured by toluidine blue.The tongue of mouse were pathologically observed.The activities of superoxide dismutase,catalase(CAT),and glutathione peroxidase and the level of malondialdehyde in tongue tissue were determined.The levels of tumor necrosis factorα(TNF-α),interleukin(IL)-1βand IL-6 in tongue tissue were determined by enzyme linked immunosorbent assay.The distribution and positive expression of phosphorylated histone H2AX(γ-H2AX)and nuclear factor-erythroid 2-related factor 2 were determined by immunohistochemistry.Results Curcumin-VE hydrogel had a porous network structure and the gelation temperature was 30℃,the swelling rate was close to 300%,the gel degradation rate was up to 95%aft

关 键 词：姜黄素 维生素E 温敏水凝胶 放射性口腔黏膜炎 抗氧化 抗炎 小鼠 

分 类 号：R318.08[医药卫生—生物医学工程] R781.5[医药卫生—基础医学]