补肾通蚀丸通过调控Nrf2/SLC7A11/GPX4通路介导铁死亡对酒精性股骨头坏死大鼠成骨功能障碍的影响  

Effects of Bushen Tongshi Pills on osteogenic dysfunction of alcohol-induced femoral head necrosis rats by regulating ferroptosis mediated through activating Nrf2/SLC7A11/GPX4 pathway

作　　者：丁强 刘金富 田照 容向宾[3] 郭良 王伟伟 李豪 牛驰程 李佳侣 曾平[2] DING Qiang;LIU Jinfu;TIAN Zhao;RONG Xiangbin;GUO Liang;WANG Weiwei;LI Hao;NIU Chicheng;LI Jialv;ZENG Ping(The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530000,China;The First Clinical Medical College of Guangxi University of Chinese Medicine,Nanning 530000,China;Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530000,China)

机构地区：[1]广西中医药大学第一临床医学院,南宁530000 [2]广西中医药大学第一附属医院,南宁530000 [3]广西中医药大学附属瑞康医院,南宁530000

出　　处：《中华中医药杂志》2024年第5期2316-2322,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82160913);广西壮族自治区级博士创新课题(No.YCBZ2023152)。

摘　　要：目的:探讨补肾通蚀丸通过抑制成骨细胞铁死亡促进酒精性股骨头坏死(AIONFH)大鼠股骨头修复的机制。方法:雄性SD大鼠36只,随机分为对照组、模型组、治疗组(补肾通蚀丸1.2 g/kg),每组12只,使用Lieber-DeCarli酒精液体饲料喂养制备AIONFH大鼠模型。Micro-CT扫描测量相关骨组织学分数;肉眼观察股骨头大体形态;HE染色观察股骨头组织病理形态学;生化试剂盒检测血清与股骨头组织中丙二醛(MDA)、谷胱甘肽(GSH)、总铁离子浓度水平;RT-qPCR、Western Blot分别检测核红系转录因子2(Nrf2)、溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)、碱性磷酸酶(ALP)、骨钙素(OCN)、Ⅰ型胶原蛋白(Collagen-Ⅰ)mRNA和蛋白表达量。结果:与模型组比较,治疗组大鼠股骨头骨质丢失情况减轻(P<0.05),股骨头组织病理学改变减轻,血清与股骨头组织中MDA、总铁离子浓度水平显著降低(P<0.05),GSH水平显著升高(P<0.05),Nrf2、SLC7A11、GPX4、ALP、OCN、Collagen-ⅠmRNA和蛋白相对表达量显著增加(P<0.05)。结论:补肾通蚀丸可能通过激活Nrf2/SLC7A11/GPX4通路抑制成骨细胞铁死亡,促进AIONFH大鼠股骨头成骨修复能力。Objective:To investigate the mechanism of Bushen Tongshi Pills in promoting the repair of alcoholic femoral head necrosis(AIONFH)in rats by inhibiting ferroptosis of osteoblasts.Methods:Thirty-six male SD rats were randomly divided into control group,model group and treatment group(Bushen Tongshi Pills,1.2g/kg),12 rats in each group were fed Lieber-DeCarli alcohol liquid feed to prepare alcoholic femoral head necrosis rat model.The relevant bone tissue scores were measured by Micro-CT scan.Gross morphology of femoral head was observed by naked eye.The histopathology of femoral head was observed by HE staining.The concentrations of malondialdehyde(MDA),glutathione(GSH)and total iron ions in serum and femoral head tissue were detected by biochemical kit.The mRNA and protein expressions of nuclear erythroid transcription factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),alkaline phosphatase(ALP),osteocalcin(OCN)and Collagen-Ⅰwere detected by RT-qPCR,Western Blot analysis.Results:Compared with the model group,the bone loss and histopathological changes of the femoral head in the treatment group were alleviated(P<0.05),the concentration levels of MDA and total iron ions in serum and femoral head tissue were significantly decreased(P<0.05),and the level of GSH was significantly increased(P<0.05).The mRNA and protein relative expressions of Nrf2,SLC7A11,GPX4,ALP,OCN and Collagen-Ⅰwere significantly increased(P<0.05).Conclusion:Bushen Tongshi Pills may inhibit ferroptosis of osteoblasts by activating Nrf2/SLC7A11/GPX4 pathway,and promote osteogenic repair ability of femoral head in AIONFH rats.

关 键 词：补肾通蚀丸 酒精性股骨头坏死 成骨细胞 铁死亡 核红系转录因子2/溶质载体家族7成员11/谷胱甘肽过氧化物酶4通路 

分 类 号：R285.5[医药卫生—中药学]