杜仲-续断药对通过调控铁死亡途径对去卵巢骨质疏松症大鼠的保护作用及机制研究  

Protective Effect and Mechanism of Duzhong(Eucommiae Cortex)-Xuduan(Dipsaci Radix)Medicinal Pair on Ovariectomized Osteoporosis Rats by regulating Ferroptosis Pathway

作　　者：李新春 胡万钧[1] 甘发荣[1] 叶宝飞[1] 吴多艺[1] 江晓兵[2] LI Xinchun;HU Wanjun;GAN Farong;YE Baofei;WU Duoyi;JIANG Xiaobing(Hainan Provincial Hospital of Traditional Chinese Medicine,Haikou 570203,Hainan,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510403,Guangdong,China)

机构地区：[1]海南省中医院,海南海口570203 [2]广州中医药大学第一附属医院,广东广州510403

出　　处：《中华中医药学刊》2023年第9期103-106,I0036,I0037,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81774338)。

摘　　要：目的观察杜仲-续断药对对去卵巢骨质疏松症大鼠骨的保护作用及机制研究。方法40只SD大鼠随机分为假手术组、模型组、中药组、雌激素组,每组10只。假手术组仅切除卵巢旁部分脂肪组织,剩余大鼠均切除双侧卵巢建立去卵巢骨质疏松(Ovariectomized osteoporosis,OVX-OP)症模型。中药组0.52 g/kg灌胃,雌激素组采用炔雌醇10μg/kg灌胃,假手术组、模型组灌胃等量生理盐水。酶联免疫吸附测定(ELISA)法检测血清雌二醇(Serum estradiol,E2)、骨钙素(Osteocalcin,OC)含量;双能X射线动物骨密度分析仪检测大鼠股骨骨密度值;苏木精-伊红(HE)染色观察各组大鼠骨组织形态;蛋白免疫印迹法(Western Blot)检测股骨组织尼克酰胺腺嘌呤二核苷酸磷酸氧化酶1(NADPH oxidase1,NOX1)、上游信号抑癌基因(p53)、谷胱甘肽过氧化酶4(Glutathione Peroxidase 4,GPX4)和铁蛋白重链(Ferritin heavy chain1,FTH1)蛋白表达。结果与假手术组相比,模型组股骨密度、E2水平、GPX4和FTH1蛋白水平显著降低(P<0.01),OC水平、NOX1、p53蛋白水平显著增加(P<0.01);与模型组相比,中药组和雌激素组股骨密度、E2水平、GPX4和FTH1蛋白水平显著升高(P<0.01),OC水平、NOX1、p53蛋白水平显著降低(P<0.01)。结论杜仲-续断药对可增加去卵巢骨质疏松大鼠股骨骨密度、减轻骨质疏松,该作用可能与抑制股骨铁死亡有关。Objective To investigate the effects and mechanism of Duzhong(Eucommiae Cortex)-Xuduan(Dipsaci Radix)medicinal pair on the bone histomorphometry of the ovariectomized osteoporosis(OVX-OP)rats.Methods Forty SD rats were randomly divided into 4 groups;sham operation control(sham)group,model group,medicinal pair group[0.52 g/(kg·d)],es-trogen group[10μg/(kg·d)](n=10 per group).Rats in the sham operation only underwent removal of adipose tissue adja-cent to the ovary,and the other 30 rats were used to make OVX-OP rat models by bilateral ovariectomy.The rats were adminis-tered by gavage.Sham group and OVX-OP group were given the same amount of normal saline.The intervention lasted for 12 weeks.The levels of serum estradiol and osteocalcin were measured by enzyme-linked immunosorbent assay.Bone mineral den-sity of the femur was measured by dual energy X-ray animal bone mineral density meter.HE staining of femur was used to ob-serve the morphology of bone.The expressions of nicotinamide adenine dinucleotide phosphooxidase 1(NOX1),upstream signal tumor suppressor gene(p53),glutathione peroxidase 4(GPX4)and ferritin heavy chain(FTH1)were detected by Western Blot method.Results After treatment,the bone mineral density,serum estradiol and GPX4 and FTH1 protein levels were significantly lower in the model group than those in the sham group(P<0.01),while serum osteocalcin and NOX1 and p53 protein levels were significantly higher in the model group(P<0.01).Compared with those in the model group,serum estradiol and GPX4 and FTH1 protein levels were significantly increased(P<0.01),while serum osteocalcin and NOX1 and p53 protein levels were sig-nificantly decreased(P<0.01)in medicinal pair group and estrogen group.Conclusion Duzhong(Eucommiae Cortex)-Xuduan(Dipsaci Radix)medicinal pair can increase the bone mineral density of the femur,improve the biomechanical condition and re-lieve osteoporosis in OVX-OP rats,which may be related to the inhibition of ferroptosis in the femur.

关 键 词：杜仲 续断 骨质疏松症 去卵巢大鼠 铁死亡 

分 类 号：R285.5[医药卫生—中药学]