基于代谢组学探究电针干预去势大鼠骨质疏松的起效机制研究  

Mechanism of EA Intervention on Osteoporosis in Ovariectomized Rats Based on Metabolomics

作　　者：屈媛媛 杨添淞[3,4] 冯楚文 孙忠人 林楚华[1] 王庆勇 马帅 秦鸿宇[2] 鲍圣涌 QU Yuanyuan;YANG Tiansong;FENG Chuwen;SUN Zhongren;LIN Chuhua;WANG Qingyong;MA Shuai;QIN Hongyu;BAO Shengyong(Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen 518020,China;The Second Clinical Medical College,Heilongjiang University of Chinese Medicine,Harbin 150001,China;The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China;Heilongjiang Provincial Key Laboratory of Clinical(Encephalopathy)Neurobiology of Acupuncture and Moxibustion,Harbin 150040,China)

机构地区：[1]深圳市人民医院,暨南大学第二临床医学院,南方科技大学第一附属医院,广东深圳518020 [2]黑龙江中医药大学第二临床医学院,黑龙江哈尔滨150001 [3]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [4]黑龙江省针灸临床(脑病)神经生物学重点实验室,黑龙江哈尔滨150040

出　　处：《针灸临床杂志》2024年第4期73-81,共9页Journal of Clinical Acupuncture and Moxibustion

基　　金：深圳市基础研究专项(自然科学基金)-基础研究面上项目,编号:JCYJ20190806154407158。

摘　　要：目的:利用LC-MS技术探究电针对去势骨质疏松大鼠粪便代谢物的影响,解析其起效机制。方法:SD大鼠随机分为假手术组(Con)、模型组(Mod)、电针A组(MA)与电针B组(MB)。切除双侧卵巢建立去势大鼠骨质疏松模型。MA、MB接受电针治疗,1次/d,连续治疗6 d后休息1 d。MA治疗4周,MB治疗8周。治疗结束后,检测胫骨和椎骨骨密度(BMD),靶向代谢组学定量血浆E2和HIF-1α,非靶向代谢组学呈现粪便代谢物轮廓及特征。结果:与Con相比,Mod大鼠BMD、E2水平下降,HIF-1α水平升高(P<0.01)。与Mod相比,MA、MB的BMD和E2均升高(P<0.01),MA和MBHIF-1α水平下降(P<0.05或P<0.01);且MB在BMD、E2和HIF-1α水平改善方面均优于MA,差异均具有统计学意义(p<0.05或P<0.01)。PCA和OPLS-DA结果显示各组间代谢物差异有统计学意义;治疗组排名前10的差异代谢物中,MA中6个回调,MB全部回调;KEGG分析发现,Con和Mod差异代谢物的显著富集通路主要为Vitamin digestion and absorption,电针干预后为Bile secretion通路。结论:电针可显著改变去势骨质疏松大鼠粪便代谢物,而且可能通过升高E2水平来抑制HIF-1α活性进而减轻体内氧化炎症反应,从而改善骨质,粪便代谢物主动或被动参与其中。Objective:To analyze the effect of electro-acupuncture(EA) on fecal metabolites of ovariectomized osteoporosis rats,and to explore its action mechanism based on LC-MS technology.Methods:SD rats were randomly divided into the sham operation group,the model group,the EA group A and the EA group B.Osteoporosis model was established by bilateral ovariectomy.The EA group A and the EA group B received EA treatment,once a day,and rested for 1 day after 6 consecutive days of treatment.The EA group A was treated for 4 weeks and the EA group B was treated for 8 weeks.Bone mineral density of tibia and vertebra was measured,and targeted metabolomics was used to quantify plasma E2 and HIF-1α,and non-targeted metabolomics was used to present profile and characteristics of fecal metabolites.Results:Compared with those in the sham operation group,the levels of BMD and E2 were decreased,and the level of HIF-1α was increased in the model group(P<0.01).Compared with those in the model group,the levels of BMD and E2 were increased(P<0.01),the level of HIF-1α was decreased in the EA group A and the EA group B(P<0.05,P<0.01);the improvements in BMD,E2 and HIF-1α were more significant in the EA group B than those in the EA group A(P<0.05,P<0.01).The results of PCA and OPLS-DA showed that there were significant differences in metabolites among groups;among the top 10 differential metabolites in the treatment groups,there were 6 callbacks in the EA group A and 10 callbacks in the EA group B.KEGG analysis found that the significant enrichment pathway of differential metabolites in the sham operation group and the model group was mainly about vitamin digestion and absorption,and the significant enrichment pathway of differential metabolites after EA intervention was mainly bile secretion pathway.Conclusion:EA significantly changes the fecal metabolites of ovariectomized osteoporosis rats,and may inhibit HIF-1α activity by increasing E2 level,thereby reducing oxidative inflammatory reaction to improve bone,and fecal metabolites activel

关 键 词：骨质疏松 去势大鼠 电针 代谢组学 粪便 

分 类 号：R245.97[医药卫生—针灸推拿学]