【作者】 郑海蓉； 闫正； 宋世婧； 步瑜婷； 张伟； 谢琪； 王勇； 路江浩； 贾晓萌； 杨雅茗； 刘志英； 雷敏；

【Author】 Zheng Hairong;Yan Zheng;Song Shijing;Bu Yuting;Zhang Wei;Xie Qi;Wang Yong;Lu Jianghao;Jia Xiaomeng;Yang Yaming;Liu Zhiying;Lei Min;School of Public Health, Hebei Medical University;Hebei Medical University;Department of Radiology, Hebei Medical University Third Hospital;Department of Nutrition, The Fourth Hospital of Hebei Medical University;Department of Research, Hebei Medical University Third Hospital;R & D Center,Hebei Inatural Biotech Co., Ltd;Comprehensive Supervision and Service Center of Hebei Provincial Health Commission;Department of Nutrition, Southwest Hospital, Third Military Medical University (Army Medical University), The First Affiliated Hospital of PLA Army Medical University;InteIntegrating Traditional Chinese and Western Medicine to Treat Disease Prevention Center, Hebei Medical University Third Hospital;Hebei Provincial Center for Innovation in Evaluation and Intervention of Preventive Diseases;

【机构】 河北医科大学公共卫生学院； 河北医科大学； 河北医科大学第三医院放射科； 河北医科大学第四医院营养科； 河北医科大学第三医院研究部； 河北一然生物技术有限公司研发中心； 河北省卫生健康委员会综合监督服务中心； 陆军军医大学西南医院营养科； 河北医科大学第三医院中西医结合治未病中心； 河北省未病测评与干预技术创新中心；

【摘要】 目的研究两歧双歧杆菌TMC3115是否可以通过抑制氧化应激-JAK2/STAT3通路来改善糖皮质激素诱导的骨质疏松症。方法将SD大鼠随机分为空白对照组、模型组和TMC3115治疗组。模型组和TMC3115治疗组均进行骨质疏松造模:肌注地塞米松,每周2次,连续8周;空白对照组肌注同等剂量的生理盐水,每周2次,连续8周。干预结束后,TMC3115治疗组大鼠灌胃益生菌活菌悬液,持续8周;空白对照组和模型组灌胃同等剂量的生理盐水。检测各组大鼠右侧股骨的骨密度、骨组织病理学、骨组织p22、gp91、p-Syk、p-Src、p-JAK2、p-STAT3蛋白表达水平。将小鼠骨髓源性巨噬细胞(BMDMs)分为空白对照组、地塞米松组、TMC3115组、H2O2组、TMC3115+H2O2组,观察p22、gp91、p-Src、p-JAK2、p-STAT3在BMDMs中的表达水平,免疫荧光法观察BMDMs中STAT3蛋白的表达。使用不同浓度TMC3115进行成骨诱导培养,观察不同浓度的TMC3115作用下BMDMs组织中gp91、p-Syk、p-Src、p-JAK2、p-STAT3、NFATc1、MMP9的蛋白表达水平以及p-STAT3、NFATc1蛋白表达水平。结果在动物实验中,与模型组比较,TMC3115干预组骨密度和骨小梁结构明显改善,p22、gp91、p-Syk、p-Src、p-JAK2、p-STAT3蛋白表达水平显著降低(P<0.05)。细胞实验中,与地塞米松组相比,TMC3115组BMDMs中p22、gp91、p-Syk、p-Src、p-JAK2、p-STAT3、NFATc1、OSCAR和MMP9蛋白表达水平显著降低(P<0.05);免疫荧光实验中,TMC3115组BMDMs中STAT3蛋白表达水平较地塞米松组显著降低(P<0.05)。随着两歧双歧杆菌TMC3115浓度的增加,p-STAT3和NFATc1蛋白表达水平逐渐降低(P<0.05)。结论两歧双歧杆菌TMC3115可通过抑制氧化应激-JAK2/STAT3通路改善糖皮质激素诱导的骨质疏松症。更多还原

【Abstract】 To investigate whether Bifidobacterium bifidum TMC3115 can improve glucocorticoid-induced osteoporosis by inhibiting the oxidative stress-JAK2/STAT3 pathway. SD rats were randomly divided into a blank control group, a model group, and a TMC3115 treatment group. The model group and the TMC3115 treatment group were both modeled for osteoporosis: intramuscular injection of dexamethasone twice a week for 8consecutive weeks; the blank control group was intramuscularly injected with the same dose of normal saline twice a week for 8 consecutive weeks. After the intervention, the TMC3115 treatment group was given oral administration of live probiotic suspension for 8 weeks; the blank control group and the model group were given oral administration of the same dose of normal saline. The bone mineral density, bone histopathology, and protein expression levels of p22, gp91, p-Syk, p-Src, p-JAK2, and p-STAT3 in the right femur of each group of rats were detected. Mouse bone marrow-derived macrophages(BMDMs) were divided into a blank control group, a dexamethasone group, a TMC3115 group, an H2O2 group, and a TMC3115 + H2O2 group. The expression levels of p22, gp91, p-Src, p-JAK2, p-STAT3 in BMDMs were observed, and the expression of STAT3 protein in BMDMs was observed by immunofluorescence. Different concentrations of TMC3115 were used for osteogenic induction culture, and the protein expression levels of gp91, p-Syk, p-Src, p-JAK2, p-STAT3, NFATc1, and MMP9in BMDMs tissues and the protein expression levels of p-STAT3 and NFATc1 were observed. In the animal experiments, compared with the model group, the bone density and trabecular structure in the TMC3115intervention group were significantly improved, and the protein expression levels of p22, gp91, p-Syk, p-Src,p-JAK2, and p-STAT3 were significantly decreased(P<0.05). In the cell experiments, compared with the dexamethasone group, the protein expression levels of p22, gp91, p-Syk, p-Src, p-JAK2, p-STAT3, NFATc1,OSCAR, and MMP9 in BMDMs in the TMC3115 group were significantly decreased(P<0.05); in the immunofluorescence experiments, the expression level of STAT3 protein in BMDMs in the TMC3115 group was significantly lower than that in the dexamethasone group(P<0.05). With the increase of the concentration of Bifidobacterium bifidum TMC3115, the protein expression levels of p-STAT3 and NFATc1 gradually decreased(P<0.05). Bifidobacterium bifidum TMC3115 can improve glucocorticoid-induced osteoporosis by inhibiting the oxidative stress-JAK2/STAT3 pathway.更多还原