基于Notch1-Hes1-Prdx蛋白家族通路探究强骨胶囊治疗绝经后骨质疏松的炎症及氧化应激机制  

Exploration on the mechanism of inflammation and oxidative stress of Qianggu Capsules in the treatment of postmenopausal osteoporosis based on the Notch1-Hes1-Prdx protein family pathway

作　　者：鲁林[1] 方虹 LU Lin;FANG Hong(Department of Orthopedics,Wuhan Hospital of Traditional Chinese Medicine,Hubei Province,Wuhan 430000,China;Department of Gynecology,Hubei Provincial Hospital of Traditional Chinese Medicine Affiliated Hospital of Hubei University of Chinese Medicine Hubei Institute of Traditional Chinese Medicine,Hubei Province,Wuhan 430000,China)

机构地区：[1]武汉市中医医院骨科,湖北武汉430000 [2]湖北省中医院湖北中医药大学附属医院湖北省中医药研究院妇科,湖北武汉430000

出　　处：《中国医药导报》2023年第23期8-15,共8页China Medical Herald

基　　金：湖北省自然科学基金创新发展联合基金项目(2022CFD150);湖北省中医药管理局中医药科研项目(ZY2023F009);湖北省武汉市卫生健康委员会科研计划资助项目(WZ20Q09)。

摘　　要：目的基于Notch1-Hes1-Prdx蛋白家族通路探究强骨胶囊治疗绝经后骨质疏松(PMOP)的炎症及氧化应激机制。方法60只5月龄清洁级雌性SD大鼠,体重(300±20)g,采用随机数字表法分为假手术组,模型对照组,阳性对照组及强骨胶囊低、中、高剂量组,每组10只。除假手术组外,其余大鼠通过切除双侧卵巢建立PMOP模型,假手术组仅切除双侧卵巢周边脂肪组织。阳性对照组经皮下注射200μg/kg雌二醇,2次/周;强骨胶囊低、中、高剂量组分别予以100、200、300 mg/(kg·d)强骨胶囊灌胃;假手术组及模型对照组灌胃等量生理盐水,连续治疗12周。比较各组大鼠股骨骨密度(BMD)值,血浆炎症标志物[白细胞介素(IL)-1β、IL-6、IL-8、IL-17、肿瘤坏死因子-α(TNF-α)]、氧化应激标志物水平[单胺氧化酶A(MAOA)、总抗氧化能力(T-AOC)、高级氧化蛋白产物(AOPP)、超氧化物歧化酶(SOD)]及Jagged1、Notch1、Hes1、Prdx蛋白家族(Prdx1~6)的蛋白表达水平;RT-qPCR及Western blot测定外周血单个核细胞(PBMC)及骨组织中的Jagged1、Notch1、Hes1及Prdx1~6 mRNA及蛋白表达。结果与假手术组比较,模型对照组大鼠BMD值、T-AOC、SOD水平降低,IL-1β、IL-6、IL-8、IL-17、TNF-α、MAOA、AOPP水平升高;血浆、PBMC及骨组织中Jagged1、Notch1、Hes1表达水平升高,Prdx1、Prdx6表达水平降低(P<0.05)。与模型对照组比较,强骨胶囊中、高剂量组大鼠BMD值、T-AOC和SOD水平升高,IL-1β、IL-6、IL-8、IL-17、TNF-α、MAOA、AOPP水平降低;血浆、PBMC及骨组织中Jagged1、Notch1、Hes1表达水平降低,Prdx1、Prdx6表达水平升高(P<0.05)。与强骨胶囊低剂量组比较,强骨胶囊中、高剂量组大鼠股骨BMD值、T-AOC和SOD水平升高(P<0.05),IL-1β、IL-6、IL-8、IL-17、TNF-α、MAOA、AOPP水平降低;血浆、PBMC及骨组织中Jagged1、Notch1、Hes1表达水平降低,Prdx1、Prdx6表达水平升高(P<0.05)。与强骨胶囊中剂量组比较,强骨胶囊高剂量组大鼠Objective To explore the mechanism of inflam-mation and oxidative stress of Qianggu Capsules in the treatment of postmenopausal osteoporosis(PMOP)based on Notch1 Hes1-Prdx protein family pathway.Methods Sixty five-month-old specific pathogen free female SD rats with body mass of(300±20)g were divided into sham operation group,model control group,positive control group,and Qianggu Capsules low,medium,and high dose groups of by random number table method,with 10 rats in each group.Except for the sham operation group,the PMOP model was established by bilateral ovaries resection,and only peripheral adipose tissue of bilateral ovaries was removed in the sham operation group.The positive control group was subcutaneously injected with 200μg/kg Estradiol,twice a week.Qianggu Capsules low,medium,and high dose groups were given 100,200,and 300 mg/(kg·d)Qianggu Capsules by gavage,respectively;the sham operation group and model control group was given the same amount of physiological saline by gavage,the treatment lasted for 12 weeks.Bone mineral density(BMD)value,plasma inflammatory markers(interleukin[IL]-1β,IL-6,IL-8,IL-17,tumor necrosis factor-α[TNF-α]),oxidative stress markers(monoamine oxidase-A[MAOA],total antioxidant capacity[T-AOC],advanced oxidation protein products[AOPP],superoxide dismutase[SOD]),and the protein expression level of Jagged1,Notch1,Hes1,and Prdx protein family(Prdx1-6)were compared among all groups;the mRNA and protein expressions of Jagged1,Notch1,Hes1,and Prdx1-6 in peripheral blood mononuclear cells(PBMC)and bone tissue were determined by RT-qPCR and Western blot.Results Compared with sham operation group,BMD value,T-AOC,and SOD levels of rats were decreased,IL-1β,IL-6,IL-8,IL-17,TNF-α,MAOA,and AOPP levels of rats were increased;the expression levels of Jagged1,Notch1,and Hes1 in plasma,PBMC,and bone tissue of rats were increased,while the expression levels of Prdx1 and Prdx6 of rats were decreased in model control group(P<0.05).Compared with model control group,BMD value,T-AOC,and SOD l

关 键 词：强骨胶囊 Notch1-Hes1-Prdx蛋白家族通路 绝经后骨质疏松 炎症 氧化应激 

分 类 号：R589.5[医药卫生—内分泌]