鹿角胶对激素性股骨头坏死模型大鼠的治疗作用:粪便代谢组学分析  

Therapeutic effect of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rat models:fecal metabolomics analysis

作　　者：柴金莲 孙铁锋[2] 李威 张博淳 李广政 周忠起 梁学振 王平[2] Chai Jinlian;Sun Tiefeng;Li Wei;Zhang Bochun;Li Guangzheng;Zhou Zhongqi;Liang Xuezhen;Wang Ping(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;Shandong Provincial Research Institute of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;First College of Clinical Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong Province,China;College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;Department of Orthopedic Microsurgery,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China)

机构地区：[1]山东中医药大学药学院,山东省济南市250014 [2]山东省中医药研究院,山东省济南市250014 [3]山东中医药大学第一临床医学院,山东省济南市250355 [4]山东中医药大学中医学院,山东省济南市250014 [5]山东中医药大学附属医院显微骨科,山东省济南市250014

出　　处：《中国组织工程研究》2025年第29期6187-6197,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(82205154),项目负责人:梁学振;山东省自然科学基金青年项目(ZR2021QH004、ZR2024MH156),项目负责人:梁学振;山东省自然科学基金项目(ZR2020MH386),项目负责人:王平。

摘　　要：背景:课题组前期研究表明,鹿角胶中的核心蛋白聚糖可进入骨,促进骨髓间充质干细胞的增殖与成骨分化,对股骨头坏死具有较好的修复作用。目的:通过粪便非靶向代谢组学方法探讨鹿角胶对大鼠激素性股骨头坏死的治疗作用及潜在机制。方法:采用随机数字表法将30只SD大鼠随机分为3组:对照组(n=10)右侧臀肌注射生理盐水(每周前3 d注射,连续注射3周),同时给予纯净水灌胃(1次/d,连续灌胃6周);模型组(n=10)右侧臀肌注射甲泼尼龙琥珀酸钠(每周前3 d注射,连续注射3周)建立激素性股骨头坏死模型,同时给予纯净水灌胃(1次/d,连续灌胃6周);鹿角胶组(n=10)同样建立激素性股骨头坏死模型,同时给予鹿角胶灌胃(1次/d,连续灌胃6周)。灌胃结束后收集盲肠粪便与股骨头,分别进行粪便代谢组学分析与骨组织Micro-CT、苏木精-伊红染色。结果与结论:①代谢组学分析结果显示,鹿角胶组与模型组相比共233种差异代谢物,具有显著差异和明确注释的代谢物共65个,其中脂质和氨基酸类代谢物含量显著升高,胆酸、硫酸固醇脂、麻黄碱、次黄嘌呤、甜菜碱、左旋肉碱、B-鼠胆酸、胞啶、4-嘧啶酸、牛磺酸、N-乙酰-d-葡萄糖胺、丁酸是影响度最高的几种代谢物(变量权重值VIP>5),牛磺酸和次牛磺酸的代谢途径在代谢调控网络中的重要性最高(通路影响因子=0.42857)。②骨组织Micro-CT扫描结果显示模型组与鹿角胶组大鼠股骨头均出现不同程度的损伤,股骨头轮廓欠规整,股骨头软骨下骨中的骨小梁缺失和紊乱,部分可见囊性变结构;与模型组相比,鹿角胶组大鼠骨小梁损伤程度较轻。苏木精-伊红染色结果显示,模型组和鹿角胶组大鼠股骨头软骨下骨的骨小梁稀疏或中断,空骨陷窝率和脂肪细胞侵袭增加;与模型组相比,鹿角胶组大鼠股骨头软骨下骨的空骨陷窝率和脂肪细胞侵袭有所减少。③结果�BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Colla can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Colla group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Colla gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Colla and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP>5).The metabolic pathways of taurine and hypotaurine were crucial

关 键 词：鹿角胶 激素性股骨头坏死 代谢组学 胆汁酸代谢 牛磺酸 工程化组织构建 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R285.5