基于Notch信号通路探讨壮骨止痛方对去势大鼠骨质疏松的影响  

Effects of Zhuanggu Zhitong Prescription on osteoporosis in castrated rats based on Notch signaling pathway

作　　者：杨军 屈杰[1] 陈丽名[1] 吴彤 Yang Jun;Qu Jie;Chen Liming;Wu Tong(Basic Medical College of Shaanxi University of Chinese Medicine,Xi'an 712046,China)

机构地区：[1]陕西中医药大学基础医学院,西安712046

出　　处：《国际中医中药杂志》2025年第1期58-63,共6页International Journal of Traditional Chinese Medicine

基　　金：陕西省科技厅重点研发计划项目(2022SF-457);陕西中医药大学国家基金培育项目(2020GP39)。

摘　　要：目的探讨壮骨止痛方防治绝经后骨质疏松症的作用机制。方法将大鼠按随机数字表法分为空白组、模型组、壮骨止痛方高剂量组、壮骨止痛方中剂量组、壮骨止痛方低剂量组、雌二醇组,每组10只。除空白组外,其余各组大鼠行双侧卵巢切除术切除卵巢,以制备绝经后骨质疏松症大鼠模型。造模后第5天,空白组、模型组灌胃生理盐水,壮骨止痛方高、中、低剂量组灌胃13.2、8.2、3.3 g/kg壮骨止痛方,雌二醇组灌胃0.0167 g/100 g雌二醇水溶液,1次/d,连续12周。测定大鼠腰椎骨密度,采用免疫组化染色和Western blot检测股骨神经源性位点Notch同源蛋白1(Notch1)、JAGGED1蛋白(JAG1)重组蛋白(Jagged1)、转录因子HES-1(Hes1)蛋白表达,采用PCR检测大鼠Notch1、Jagged1、Hes1 mRNA水平。结果与模型组比较,各组大鼠骨密度升高(P<0.01),Notch1、Jagged1蛋白及mRNA水平升高(P<0.01),Hes1蛋白及mRNA水平降低(P<0.01)。结论壮骨止痛方可提高去势骨质疏松大鼠骨密度,促进大鼠股骨骨小梁增多增粗、排列紧密,促进骨形成,进而防治骨质疏松,其作用机制可能与激活Notch信号通路,上调Notch1、Jagged1蛋白,下调Hes1蛋白表达,从而促成骨分化有关。Objective To explore the mechanism of Zhuanggu Zhitong Prescription in preventing and treating postmenopausal osteoporosis.Methods Rats were randomly divided into blank group,model group,Zhuanggu Zhitong Prescription high-,medium-,and low-dosage groups,and an estradiol group,with 10 rats in each group.Except for the blank group,all other groups of rats underwent bilateral oophorectomy to remove the ovaries,in order to prepare a postmenopausal osteoporosis rat model.On the 5th day after modeling,the blank group and model group were orally administered with 0.9%NaCl physiological saline,Zhuanggu Zhitong Prescription high-,medium-,and low-dosage groups were orally administered with 13.2,8.2,and 3.3 g/kg of Zhuanggu Zhitong Prescription,and the estradiol group was orally administered with 0.0167 g/100 g estradiol aqueous solution once a day for 12 consecutive weeks.The bone density of the lumbar spine in rats was measured;immunohistochemistry and Western blot were used to detect the expressions of Notch1,Jagged1,and Hes1 proteins;PCR was used to detect the mRNA levels of Notch1,Jagged1,and Hes1 in rats.Results Compared with the model group,the bone density of rats in each group significantly increased(P<0.01),the protein and mRNA levels of Notch1 and Jagged1 increased(P<0.01),and the protein and mRNA levels of Hes1 decreased(P<0.01).Conclusions Zhuanggu Zhitong Prescription can improve bone mineral density in castrated osteoporosis rats,promote the increase and thickening of trabeculae of femoral bone in rats,promote bone formation,and further prevent osteoporosis.The mechanism may be related to the activation of Notch signaling pathway,up-regulation of Notch1 and Jagged1 proteins,and decrease of Hes1 protein expression,thus promoting bone differentiation.

关 键 词：骨质疏松 壮骨止痛方 NOTCH信号通路 大鼠 

分 类 号：R73[医药卫生—肿瘤]