机构地区:[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110033
出 处:《中国骨质疏松杂志》2025年第2期163-168,203,共7页Chinese Journal of Osteoporosis
基 金:国家自然科学基金面上项目(82174260);辽宁省科学技术厅联合基金博士科研启动项目(2023-BSBA-224);辽宁省教育厅2024年度优秀研究生项目(2024-JYTCB-039)。
摘 要:目的以中医“阳化气、阴成形”理论为出发点,探讨“阴阳互济”法介导PGC-1α对PMOP发病过程中线粒体生物发生的影响,为左、右归丸防治PMOP奠定更多理论依据。方法将100只SD大鼠随机分为SHAM、OVX、ZGW、YGW、BJL组,每组20只。除SHAM组外,其余组切除双侧卵巢,造模3 d后按组别灌胃12周。采用Micro-CT检测大鼠左侧股骨近端骨分析参数;HE染色法观察骨组织形态;ELISA法检测血清BGP、PICP的含量;比色法检测血清TRACP含量;Western Blot法检测骨髓组织中成脂相关蛋白PPARγ、C/EBPα、CD36、FSP27、Adipoq,骨髓脂肪相关蛋白PGC-1α、UCP1、DIO2、PRDM16以及线粒体生物发生相关NRF1、NRF2、TFAM蛋白表达水平。结果与SHAM组比较,OVX组BMD、BV/TV、Ct.Th、Tb.Th、Conn D表达降低(P<0.01);骨小梁稀疏变细,髓腔内脂肪细胞增多,脂滴体积变大;血清BGP、PICP、TRACP含量显著升高(P<0.01);PPARγ、C/EBPα、CD36、FSP27蛋白表达均显著上调(P<0.01),Adipoq、PGC-1α、UCP1、DIO2、PRDM16、NRF1、NRF2、TFAM蛋白表达显示下调(P<0.01)。与OVX组比较,各给药组的骨分析参数明显改善(P<0.05,P<0.01);骨小梁增粗、数量增多、骨形态结构明显增强;脂肪细胞减少;血清BGP、PICP、TRACP含量显著降低(P<0.01);PPARγ、C/EBPα、CD36、FSP27蛋白表达下调,Adiopq、PGC1-α、UCP1、DIO2、NRF1、NRF2、TFAM蛋白表达上调(P<0.05,P<0.01)。结论左、右归丸均可调控PGC-1α影响骨髓脂肪累积,提高线粒体生物发生水平以防治PMOP。Objective This experimental study is based on the theory of“Yang transforming Qi and Yin forming”in traditional Chinese medicine and explores the effects on“Yin-Yang mutual aid”methods mediating PGC-1αof mitochondrial biogenesis in the pathogenesis of PMOP,to provide more theoretical basis for the prevention and treatment of PMOP with Zuogui Pills and Yougui Pills.Methods 100 SPF level 2-month-old female SD unfertilized rats were randomly divided into SHAM group,OVX group,ZGW group,YGW group and BJL group,with 20 rats in each group.Except for the SHAM group,bilateral ovaries were removed in the other groups,and after modeling for 3 days,gastric lavage was administered to each group for 12 weeks.Micro CT was used to detect the bone analysis parameters of the left proximal femur in rats and obtain three-dimensional images;Hematoxylin-eosin(HE)staining was used to observe bone tissue morphology;Enzyme-linked immunosorbent assay(ELISA)is used to detect the levels of serum BGP and PICP;Colorimetry was used to detect the levels of serum TRACP;Western blot(WB)was used to detect expression of adipo-associated proteins PPARγ,C/EBPα,CD36,FSP27,Adipoq,brown adipose tissue(BAT)associated proteins PGC-1α,UCP1,DIO2,PRDM16,and mitochondrial biogenesis related proteins PGC-1α,NRF1,NRF2,and TFAM.Results Compared with the SHAM group,the BMD,BV/TV,Ct.Th,Tb.Th and Conn D in the OVX group were significantly decreased(P<0.01).Trabeculae are sparse and thin,fat cells in the medullary cavity are increased,and the volume of lipid droplets increases;The serum levels of BGP,PICP and TRACP were significantly increased(P<0.01).the protein expressions of PPARγ,C/EBPα,CD36 and FSP27 were significantly up-regulated,and the protein expressions of Adipoq,PGC-1α,UCP1,DIO2,PRDM16,NRF1,NRF2 and TFAM were down-regulated(P<0.01).Compared with the OVX group,BMD,BV/TV,Ct.Th,Tb.Th,and Conn D were increased in each administration group(P<0.01,P<0.05),and Tb.Sp decreased(P<0.01,P<0.05);Trabecular bone thickened,the number increased,the bone
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