豨莶草调节Nrf2介导的抗氧化途径对去卵巢大鼠骨质疏松症的影响  

Effects of Herba Siegesbeckia on Osteoporosis in Ovariectomized Rats by Regulating Nrf2-Mediated Antioxidant Pathway

作　　者：李光辉 王前进 王俊杰 李明 LI Guanghui;WANG Qianjin;WANG Junjie;LI Ming(Henan Hospital of Traditional Chinese medicine,the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450053,China)

机构地区：[1]河南省中医院,河南中医药大学第二附属医院,郑州450053

出　　处：《世界科学技术-中医药现代化》2024年第2期360-366,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：河南省中医管理局中医药科学研究专项课题(2019JDZX041);自制改良弹力塑性夹板治疗桡骨远端骨折(伸直型)的临床研究,负责人:李光辉。

摘　　要：目的探讨豨莶草对骨质疏松症大鼠抗氧化和保护骨组织的作用机制。方法采用双侧卵巢切除术法制备骨质疏松症大鼠模型,分为模型组(Model)、ML385(Nrf2抑制剂)组、豨莶草组(Hsb)和豨莶草+ML385组(Hsb+ML385),另设置假手术组(Sham),每组12只。给予相应药物干预,连续干预12周。采用Micro CT测定各组大鼠骨密度(Bone mineral density,BMD)及骨小梁微结构参数变化;HE染色观察股骨组织病理学改变;ELISA法检测大鼠血清中抗酒石酸酸性磷酸酶-5b(TRACP-5b)和碱性磷酸酶(Alkaline phosphatase,ALP)水平;化学法检测大鼠血清中活性氧(Reactive oxidative stress,ROS)、超氧化物歧化酶(Superoxide dismutase,SOD)及丙二醛(Malondialdehyde,MDA)水平;采用qRT-PCR和Western bolt分别检测骨组织中Nrf2和HO-1 mRNA和蛋白表达水平。结果与Sham组比较,Model组大鼠骨组织结构破坏明显,BMD、血清ALP水平及SOD活性显著降低(P<0.05),TRACP-5b、MDA及ROS水平显著增加(P<0.05),而骨组织中Nrf2和HO-1 mRNA和蛋白表达水平显著下调(P<0.05)。与Model组比较,Hsb组大鼠骨组织结构损伤明显改善,BMD及血清ALP水平及SOD活性显著升高(P<0.05),TRACP-5b、MDA及ROS水平明显降低(P<0.05),骨组织中Nrf2和HO-1 mRNA和蛋白表达水平显著上调(P<0.05),而ML385组大鼠上述各指标进一步升高/降低。与Hsb组比较,Hsb+ML385组大鼠骨组织结构破坏明显,BMD、血清ALP水平及SOD活性又显著降低(P<0.05),TRACP-5b、MDA及ROS水平又显著增加(P<0.05),而骨组织中Nrf2和HO-1 mRNA和蛋白表达水平又显著下调(P<0.05)。结论豨莶草可以降低氧化应激水平,改善大鼠骨质疏松症,其作用机制可能与激活Nrf2/HO-1信号有关。Objective To investigate the mechanism of antioxidant and bone tissue protection of herba siegesbeckia in rats with osteoporosis.Methods The rat model of osteoporosis was prepared by bilateral oophoectomy and then divided into model group,ML385(Nrf2 inhibitor)group,herba siegesbeckia group and herba siegesbeckia+ML385 group,another Sham operation group were set,12 in each group.The corresponding drugs intervention were given for 12 weeks.Micro CT was used to determine the changes of bone mineral density(BMD)and trabecular microstructure parameters;Hematoxylin eosin(HE)staining was used to detect the pathological changes of femur bone tissue;Enzyme-linked immunosorbent assay(ELISA)was applied to evaluate the levels of acid tartaric acid phosphatase-5b(TRAP-5b)and alkaline phosphatase(ALP)in serum.Chemical methods were used to detected the levels of reactive oxidative stress(ROS),superoxide dismutase(SOD)and malondialdehyde(MDA)in serum;Real time PCR and western blotting were used to detected the expression levels of Nrf2 and HO-1 in bone tissues.Result Compared with the Sham group,the bone tissue structure of the model group was significantly damaged.The BMD,serum ALP level and SOD activity were significantly decreased(P<0.05),the levels of TRACP-5b,MDA and ROS were significantly increased(P<0.05),the mRNA and protein expression levels of Nrf2 and HO-1 in the bone tissues were significantly down-regulated(P<0.05).Compared with model group,the damage of bone tissue structure in herba siegesbeckiae group was significantly improved;The BMD value,serum ALP and SOD activity were significantly increased(P<0.05),and the levels of TRACP-5b,MDA and ROS were significantly decreased(P<0.05),the mRNA and protein expression levels of Nrf2 and HO-1 in bone tissue were significantly up-regulated(P<0.05),and the above indexes were further promotion/reduction in the ML385 group.Compared with herba siegesbeckiae group,the bone tissue structure of the herba siegesbeckiae+ML385 group was significantly damaged,and the BMD value,serum

关 键 词：豨莶草 骨质疏松症 Nrf2/HO-1信号通路 氧化应激 

分 类 号：R285.5[医药卫生—中药学]