参骨颗粒通过肠道菌群改善骨质疏松的研究  

A study on the treatment of osteoporosis with Shengu granules mediated by intestinal microflora

作　　者：李伟举 陈晓聪[1] 曾家莹 薛慧芝 刘军 吕朝晖[2] LI Weju;CHEN Xiaocong;ZENG Jiaying;XUE Huezhi;LIU Jun;LV Zhaohui(University of Guangzhou Traditional Chinese Medicine,Guangzhou 510405;The Second Traditional Chinese Medicine Hospital of Guangdong Province,Guangzhou 510095,China)

机构地区：[1]广州中医药大学,广东广州510405 [2]广东省第二中医院,广东广州510095

出　　处：《中国骨质疏松杂志》2024年第9期1341-1347,1352,共8页Chinese Journal of Osteoporosis

基　　金：广州市科技计划项目(202102080119);广东省中医药局科研项目(20221023);广东省名中医传承工作室建设项目(粤中医办函[2023]108号)。

摘　　要：目的从肠道菌群的变化上观察参骨颗粒对骨质疏松大鼠的治疗作用,明确其作用机制。方法36只SD大鼠,以随机法均等划分为3个组别,每组均为12只。假手术组,切除卵巢附近同等重量的脂肪,存留卵巢位置。模型组、参骨颗粒组,均开展双侧卵巢切除。参骨颗粒组,选择运用参骨颗粒溶液(12 g/kg)进行灌胃处理,其他两个组别均使用同等剂量的水,总计持续12周。ELISA法检测NTX-Ⅰ、BGP、BALP水平;Micro-CT检测骨密度及骨微结构;HE染色测定结肠位置的病理变化;16SrRNA测定肠道的菌群状态;UPLC-ESI-MS/MS测定粪便中短链脂肪酸(SCFAs);Western blot检测股骨组织中Wnt10b、β-catenin。结果与假手术组进行对比,模型组骨密度出现显著降低、骨微结构稀疏;血清NTX-Ⅰ提升,BALP以及BGP下调;结肠炎症明显,多处可见溃疡面,肠道菌群多样性及组成有所下降,短链脂肪酸浓度降低,Wnt10b、β-catenin蛋白表达降低。参骨颗粒组与模型组进行对比,骨密度有显著的提升,而且骨微结构获得显著的优化;血清中的NTX-Ⅰ水平降低,血清中BALP、BGP水平升高;结肠表面病理损伤减少,炎症得到缓解;肠道菌群多样性提高,SCFAs浓度增加,股骨组织中Wnt10b及β-catenin蛋白表达升高。结论参骨颗粒可能通过修复肠道菌群失衡,以短链脂肪酸为中介,激活Wnt/β-catenin成骨通路蛋白,改善骨质疏松。Objective To observe the therapeutic effect of Shengu granules on osteoporosis rats from the changes in intestinal flora,and to clarify its mechanism of action.Methods Thirty-six SD rats were randomly divided into three groups,each consisting of 12 animals.In the sham operation group,an equivalent amount of fat was removed while preserving the ovarian location.In both the model group and the Shengu granule group,bilateral ovariectomy was performed.The Rats in Shengu granule group received Shengu granule solution(12g/kg)by gavage.Rats in the other two groups received an equal dose of water.All the treatment lasted for a total duration of 12 weeks.Specific NTX-I,BGP,and BALP levels were measured with ELISA.Bone microstructure was assessed using micro-CT.Pathological changes in the colon location were determined with HE staining.The gut microbiota status was assessed with 16SrRNA analysis.Short-chain fatty acids(SCFAs)in feces were measured with UPLC-ESI-MS/MS.Wnt10b andβ-catenin were assessed with Western blotting.Results Compared with the sham operation group,the model group showed a significant decrease in bone mineral density and sparse bone microstructure.The serum NTX-I level increased,while BALP and BGP decreased.Significant colitis,severe ulcers,impaired intestinal flora,reduced SCFAs,and decreased levels of Wnt10b,etc.were observed.Compared with the model group,the Shengu granule granule group showed a significant increase in bone mineral density and substantial improvement in bone microstructure.The serum NTX-I level decreased,while BALP and BGP increased.Colon damage and inflammation reduced.Gut recovery was noted with increased SCFAs and an upregulation of Wnt10b,etc.Conclusion Shengu granules relieve osteoporosis by repairing the imbalance of intestinal flora and activating wnt/β-catenin osteogenic pathway proteins mediated by short-chain fatty acid.

关 键 词：参骨颗粒 Wnt/β-catein蛋白信号通路 短链脂肪酸 肠道菌群 骨质疏松症 

分 类 号：R285.5[医药卫生—中药学]