金天格胶囊治疗维甲酸诱导骨质疏松大鼠的蛋白质组学分析  

Proteomic study of Jintiange capsule in the treatment of retinoic acid-induced osteoporosis rats

作　　者：张驰 章晓云[1] 柴源 陈锋[1] Zhang Chi;Zhang Xiaoyun;Chai Yuan;Chen Feng(Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学附属瑞康医院,广西壮族自治区南宁市530011

出　　处：《中国组织工程研究》2023年第35期5634-5641,共8页Chinese Journal of Tissue Engineering Research

基　　金：金天格中青年科研培养基金(项目61),项目负责人:章晓云;广西自然科学基金(2021GXNSFAA220089),项目负责人:陈锋;广西自然科学基金(2020GXNSFBA159053),项目负责人:章晓云;广西中医药适宜技术开发与推广项目(GZSY22-36),项目负责人:章晓云;广西中医药大学2021年校级青年创新研究团队项目(2021TD001),项目负责人:章晓云;广西研究生教育创新计划资助项目(YCBZ2021075),项目负责人:张驰;黄有荣桂派中医大师培养项目(桂中医药科教发[2022]6号),项目参与人:章晓云。

摘　　要：背景:金天格胶囊抗原发性骨质疏松症的疗效已得到临床研究证据证实和临床应用指南推荐,但其抗继发性骨质疏松症的作用及靶点仍未明确。目的:探讨金天格胶囊治疗继发性骨质疏松症的药效靶点与作用机制。方法:将24只雌性SD大鼠随机分为4组,每组6只:空白组不做任何处理;模型组通过灌胃给予维甲酸建立骨质疏松模型,造模14 d后灌胃给予生理盐水;金天格组和阳性对照组通过灌胃给予维甲酸建立骨质疏松模型,造模14 d后分别灌胃给予金天格、阿仑膦酸钠,各组连续给药14 d。给药结束后,取股骨做micro-CT扫描和串联质谱标签定量蛋白质组学,采用生物信息学分析差异蛋白涉及的功能、信号通路及蛋白互作关系,并筛选核心蛋白。结果与结论:①与空白组相比,模型组大鼠股骨骨体积分数、骨小梁厚度和骨小梁数量显著降低(P<0.05),骨小梁分离度增高(P<0.05);与模型组相比,阳性对照组与金天格组大鼠股骨骨体积分数、骨小梁厚度和骨小梁数量增高(P<0.05),骨小梁分离度降低(P<0.05);②共筛选出模型组与空白组间差异蛋白2749个,涉及ATP代谢过程、缺氧反应、细胞铁离子稳态等生物学进程,铁死亡、低氧诱导因子1信号通路、脂肪酸代谢等信号通路;金天格组与模型组间差异蛋白773个,涉及骨化、过氧化氢生物合成、缺氧反应等生物学进程,低氧诱导因子1信号通路、脂肪酸代谢、氧化磷酸化等信号通路;③共得到金天格胶囊治疗骨质疏松症的靶点453个,包含转铁蛋白、核糖体蛋白S14、核糖体蛋白S21等49个一级核心蛋白,核糖体蛋白S6、核糖体蛋白S20、核糖体蛋白S28等15个二级核心蛋白;④结果显示,金天格胶囊可能通过下调长链脂酰辅酶A合成酶1、花生四烯酸-15-脂加氧酶、转铁蛋白、CREB结合蛋白抑制脂质过氧化和铁蓄积而负调控铁死亡,改善骨质疏松症大鼠的骨量减少�BACKGROUND:The therapeutic effect of Jintiange capsule on primary osteoporosis has been confirmed by clinical research evidence and recommended by clinical application guidelines,but its effects and targets against secondary osteoporosis remain unclear.OBJECTIVE:To explore the therapeutic target and mechanism of Jintiange capsule in the treatment of secondary osteoporosis.METHODS:Twenty-four female Sprague-Dawley rats were randomly divided into four groups(n=6 per group):blank group(with no treatment),model group,Jintiange capsule group,and positive control group.Animal models of osteoporosis were prepared in the latter three groups by intragastric administration of retinoic acid.Fourteen days after modeling,the model group was intragastrically given normal saline,while the Jintiange capsule and positive control groups were given Jintiange capsule and alendronate sodium,respectively,for 14 days.After treatment,the femurs were taken for micro-CT scanning and tandem mass tags quantitative proteomics.Bioinformatics was used to analyze the function,signal pathway and protein interaction of the differential proteins and to screen the core proteins.RESULTS AND CONCLUSION:Compared with the blank group,bone volume fraction,trabecular thickness and trabecular number of the femur were significantly decreased(P<0.05)and trabecular separation was significantly increased(P<0.05)in the model group.Compared with the model group,bone volume fraction,trabecular thickness and trabecular number of the femur were increased(P<0.05)and trabecular separation was decreased(P<0.05)in the positive control and Jintiange capsule groups.A total of 2749 differential proteins were screened between the model group and the blank group,involved in multiple biological processes such as ATP metabolism,hypoxia response,and cellular iron homeostasis as well as signal pathways such as ferroptosis,hypoxiainducible factor 1 signal pathway,and fatty acid metabolism.A total of 773 differential proteins were screened between Jintiange capsule group and mod

关 键 词：金天格胶囊 骨质疏松症 蛋白质组学 维甲酸 铁死亡 

分 类 号：R459.9[医药卫生—治疗学] R313[医药卫生—临床医学] R285