黄芪甲苷对去卵巢大鼠肠道菌群和骨质疏松症的影响  

Effect of astragaloside IV on intestinal flora and osteoporosis in ovariec-tomized rats

作　　者：王昊宇 姚威 梁爱迪 黄卓 张荣华[2,3] WANG Haoyu;YAO Wei;LIANG Aidi;HUANG Zhuo;ZHANG Ronghua(College of Traditional Chinese Medicine,Jinan University,Guangzhou 510632,China;College of Pharmacy,Jinan University,Guangzhou 510632,China;GuangdongProvincial Key Laboratory of Traditional Chinese Medicine Informatiza-tion,Guangzhou 510632,China;Guangzhou Zengcheng District Hostipal of Traditional Chinese Medicine,Guangzhou 511300,China)

机构地区：[1]暨南大学中医学院,广东广州510632 [2]暨南大学药学院,广东广州510632 [3]暨南大学广东省中医药信息化重点实验室,广东广州510632 [4]广州市增城区中医医院,广东广州511300

出　　处：《中国病理生理杂志》2025年第2期311-321,共11页Chinese Journal of Pathophysiology

基　　金：国家自然基金区域创新发展联合基金集成项目(No.U24A6013);国家自然科学基金面上项目(No.82274232,No.82074287);广东省基础与应用基础研究基金项目(No.2022B1515120022);广东省中医药信息化重点实验室基金资助项目(No.2021B1212040007)。

摘　　要：目的:观察黄芪甲苷(astragaloside IV,AS)对去卵巢大鼠肠道菌群和骨质疏松症的影响,分析AS治疗骨质疏松症的作用机制。方法:选用3月龄雌性SD大鼠30只,先随机选取10只为假手术(sham)组,其余20只建立双侧去卵巢(ovariectomy,OVX)模型,模型成功后随机分为OVX组和黄芪甲苷干预(AS)组,灌胃给予AS12周。使用双能X线骨密度仪检测大鼠股骨和胫骨骨密度(bone mineral density,BMD),HE染色观察股骨和结肠结构变化,免疫组化检测股骨I型胶原α1链(collagen type I alpha 1 chain,COL1A1)的表达,RT-qPCR检测股骨骨形成相关指标碱性磷酸酶(alkaline phosphatase,ALP)、COL1A1和Runt相关转录因子2(Runt-related transcription factor2,RUNX2)的mRNA表达;收集大鼠新鲜粪便,16S rDNA法检测大鼠肠道菌群基因变化。结果:与sham组相比,OVX大鼠体重增加,股骨和胫骨骨密度显著下降;HE染色结果显示OVX组骨小梁断裂,呈网状结构,骨髓腔内形成较多空洞或脂肪空泡,结肠黏膜层绒毛脱落,隐窝轻度萎缩;免疫组化染色显示,OVX组COL1A1表达显著降低;RT-qPCR检测发现ALP、COL1A1和RUNX2的mRNA表达下降。与OVX组相比较,AS组体重减轻,股骨和胫骨骨密度显著上升,且骨小梁排列规则,断裂程度较小,骨髓腔内脂肪空泡明显减少,结肠病变减轻。COL1A1蛋白表达及ALP、COL1A1和RUNX2的mRNA表达显著增加。16S rDNA结果显示,OVX组肠道菌群厚壁菌门、变形菌门、伪诺卡氏菌科、散囊菌目散囊菌科、颤螺菌科、瘤胃菌科和消化链球菌科的丰度显著增加,广古菌门、拟杆菌门和细菌科丰度显著降低,肠道菌群的物种分布多样性增加;AS干预能回调上述菌门(科),降低菌群物种分布多样性。结论:AS能够提高OVX大鼠骨密度,改善其骨微结构,促进大鼠骨形成,减轻结肠黏膜损伤,这一作用可能与其调控肠道菌群的相对丰度有关。AIM:This study aims to investigate the mechanisms through which Astragaloside IV(AS)prevents and treats osteoporosis by regulating intestinal flora.METHODS:Thirty 3-month-old female Sprague-Dawley(SD)rats were selected for the study.Ten rats were randomly assigned to a sham group,while the remaining twenty underwent bilateral ovariectomy(OVX)to simulate osteoporosis.Following the modeling,the twenty OVX rats were randomly divided into two groups:the OVX group and the AS treatment group,which received continuous gavage for 12 weeks.Bone mineral density(BMD)of the femur and lumbar vertebrae was measured using dual-energy X-ray absorptiometry(DXA).Hematoxylin-eosin(HE)staining was employed to assess the microstructure of the femur and colonic mucosa,while immu-nohistochemistry was used to measure the expression of collagen type I alpha 1 chain(COL1A1)protein in the femur.Ad-ditionally,RT-qPCR was utilized to analyze the mRNA expression of bone formation-related indicators,including alkaline phosphatase(ALP),COL1A1,and Runt-related transcription factor 2(RUNX2).Fresh fecal samples were collected from the rats for 16S rDNA sequencing to detect changes in intestinal microbiota composition.RESULTS:Compared to the sham group,OVX rats exhibited a significant increase in body weight and a marked decrease in femur and lumbar ver-tebrae bone density.HE staining revealed trabecular bone fractures with a disrupted reticular structure in the OVX group,along with the presence of numerous cavities and fat vacuoles in the bone marrow.The colonic mucosa showed signs of vil-lous shedding and mild crypt atrophy.Immunohistochemistry results demonstrated a substantial reduction in brown-yellow granules and COL1A1 expression in the OVX group.Conversely,in the AS group,there was a reduction in body weight and a significant increase in bone density of the femur and lumbar vertebrae.The trabecular architecture appeared more or-ganized,with less severe fractures compared to the OVX group.In the AS group,the number of cavities and fat vacuol

关 键 词：骨质疏松症 肠道菌群 黄芪甲苷 

分 类 号：R363.2[医药卫生—病理学] R681[医药卫生—基础医学] R574