藏药二十五味鬼臼丸介导的氧化应激改善骨代谢防治绝经后骨质疏松作用机制分析  

Analysis of the mechanism of oxidative stress improvement and prevention of postmenopausal osteoporosis mediated by Tibetan medicine Ershiwuwei Guijiu Wan

作　　者：江宇楠 孙欣雨 李凤辉[1] 马莉娜 万雅琦 李长兴[1] JIANG Yunan;SUN Xinyu;LI Fenghui;MA Lina;WAN Yaqi;LI Changxing(Medical College of Qinghai University,Xining 810001,China;Qinghai Provincial People Hospital,Xining 810007,China)

机构地区：[1]青海大学医学院,青海西宁810001 [2]青海省人民医院,青海西宁810007

出　　处：《药学研究》2024年第12期1145-1150,1162,共7页Journal of Pharmaceutical Research

基　　金：青海省科技厅项目(No.2023-ZJ-783);青海大学青年科研基金项目(No.2022-QNY-9、2023-QYY-1)。

摘　　要：目的探讨藏药二十五味鬼臼丸通过减轻氧化应激反应防治绝经后骨质疏松症的作用机制。方法将40只3月龄健康雌性SD大鼠手术去势,随机分为假手术(Sham)组、手术(OVX)组、二十五味鬼臼丸(GJ)组、盐酸雷洛昔芬(RLX)组。通过一般情况观察及比色法、ELISA法检测血清中活性氧(ROS)、总超氧化物歧化物(T-SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)与骨钙素(BGP)、β-Ⅰ型胶原交联C-末端肽(β-CTx)、β-半乳糖苷酶(β-GAL)含量;免疫组化观察成-破骨细胞活性;荧光硬组织切片观察股骨病理形态及扫描电镜观察股骨、腰椎骨微结构变化。结果与Sham组相比,OVX组大鼠出现明显骨质疏松且体重增加,骨微结构破坏明显,骨骺生长板较窄,血清SOD、GSH-Px、BGP及骨形态发生蛋白(BMP-2)活性降低(P<0.05,P<0.01),ROS、MDA、β-CTx、β-GAL及组织蛋白酶K(CTSK)活性上升(P<0.05,P<0.01);与OVX组相比,GJ、RLX组大鼠骨质疏松症状有所改善,骨吸收陷窝减少,骨小梁间距减小且排列有序,骨胶原纤维、骨骺生长板相对增厚,血清SOD、GSH-Px、BGP及BMP-2活性增加(P<0.05,P<0.01),ROS、MDA、β-CTx、β-GAL及CTSK活性下降(P<0.05,P<0.01)。结论藏药二十五味鬼臼丸能够改善绝经后骨质疏松症的骨代谢水平及骨微结构,其机制可能与降低模型大鼠体内氧化应激反应密切相关。Objective To explore the mechanism of Tibetan medicine Ershiwuwei Guijiu Wan in preventing and treating postmenopausal osteoporosis by alleviating oxidative stress.Methods Forty healthy female SD rats aged 3 months were surgically castrated and randomly divided into sham operation(Sham),operation(OVX),Ershiwuwei Guijiu Wan(GJ)and raloxifene hydrochloride(RLX)groups.The general situation was observed,and the contents of serum reactive oxygen species(ROS),total superoxide dismutase(T-SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and osteocalcin(BGP),β-type I collagen cross-linked C-terminal peptide(β-CTx)andβ-galactosidase(β-GAL)were detected by colorimetry and ELISA.The activity of osteoblasts and osteoclasts was observed by immunohistochemistry,and the pathological morphology of femurs was observed by fluorescent hard tissue sections,and the microstructural changes of femurs and lumbar vertebrae were observed by scanning electron microscopy.Results Compared with the Sham group,the rats in the OVX group had obvious osteoporosis and increased weight,obvious bone microstructural destruction,narrow epiphyseal growth plate,serum SOD,GSH-Px,BGP and bone morphogenetic protein(BMP-2)activities were significantly reduced(P<0.05,P<0.01),and the activity of ROS,MDA,β-CTx,β-GAL and osteoclast cathepsin K(CTSK)was significantly increased(P<0.05,P<0.01);Compared with the OVX group,the osteoporosis symptoms of rats in the GJ and RLX groups were improved,the bone resorption lacunae were reduced,the distance between bone trabeculae was reduced and arranged in an orderly manner,and the collagen fibers and epiphyseal growth plates were relatively thickened,and serum SOD,GSH-Px,BGP and BMP-2 activity increased significantly(P<0.05,P<0.01),ROS,MDA,β-CTx,β-GAL and CTSK activity decreased significantly(P<0.05,P<0.01).Conclusion Tibetan medicine Ershiwuwei Guijiu Wan can improve the bone metabolism level and bone microstructure of postmenopausal osteoporosis,and its mechanism may be closely related to reducing the oxid

关 键 词：藏药二十五味鬼臼丸 绝经后骨质疏松 氧化应激 骨代谢 

分 类 号：R291.408[医药卫生—民族医学]