补肾中药复方对高盐摄入去卵巢大鼠骨代谢及ENaCα、NCC和ClC-3表达的影响  

Effects of Bushen formulae on bone metabolism and ENaCα,NCC and ClC-3 expression in ovariectomized rats with high salt intake

作　　者：崔琰 孙珂焕[3] 詹小瑶 莫枢 肖雅雯 王攀攀[1] 杨丽[5] 张荣华[5] 朱晓峰[1,2] CUI Yan;SUN Kehuan;ZHAN Xiaoyao;MO Shu;XIAO Yawen;WANG Pan-pan;YANG Li;ZHANG Ronghua;ZHU Xiaofeng(The First Affiliated Hospital of Jinan University,Guangzhou 510632,China;School of Traditional Chinese Medicine,Jinan University,Guangzhou 510632,China;Shenzhen Second People's Hospital,Shenzhen 518025,China;Shenzhen Hospital of Traditional Chinese Medicine,Shenzhen 518000,China;College of Pharmacy,Jinan University,Guangzhou 510632,China)

机构地区：[1]暨南大学附属第一医院,广东广州510632 [2]暨南大学中医学院,广东广州510632 [3]深圳市第二人民医院,广东深圳518025 [4]深圳市中医院,广东深圳518000 [5]暨南大学药学院,广东广州510632

出　　处：《中国病理生理杂志》2024年第1期141-147,共7页Chinese Journal of Pathophysiology

基　　金：国家重点研发计划项目(No.2018YFC2002501);广东省中医药信息化重点实验室(No.2021B1212040007);国家自然科学基金项目(No.81973717,No.82274376);广东省自然科学基金项目(No.2022A1515011660);暨南大学博士研究生拔尖创新人才培养项目(No.2022CXB018)。

摘　　要：目的:探讨补肾中药复方(Bushen formulae,BHF)对高盐摄入去卵巢大鼠骨代谢的影响及其可能的作用机制。方法:80只SPF级SD雌性大鼠按随机数字表法分为假手术组、模型组、中高盐组、高盐组、补肾方组、补肾方+生理盐水组、补肾方+中高盐组、补肾方+高盐组,每组各10只,造模后给予不同饮食、补肾中药复方干预,中高盐饮食、高盐饮食中氯化钠添加浓度分别为2%w/w、8%w/w,补肾中药复方干预剂量为7.8 g·kg^(-1)·d^(-1),每日1次,连续给药12周。检测各组骨密度、骨微结构、骨参数、骨代谢生物标志物、骨组织病理变化情况以及采用Western blot检测骨组织上皮钠离子通道α(ENaCα)、钠-氯同向转运体(NCC)、电压门控性氯离子通道3(ClC-3)蛋白的表达。结果:与假手术组相比,模型组大鼠骨密度降低,骨微结构破坏;与模型组相比,中高盐、高盐饮食组大鼠骨微结构破坏更为明显,同时高盐组骨形成标志物骨钙素(BGP)、Ⅰ型原胶原氨基端前肽(PINP)水平显著上升(P<0.05),骨吸收标志物Ⅰ型胶原氨基端肽(NTX)、Ⅰ型胶原羧基端肽(CTX)、抗酒石酸酸性磷酸酶(TRACP)均显著增加(P<0.05),骨代谢处于高转换状态;高盐饮食加速骨小梁结构的破坏,Western blot结果显示高盐饮食引起股骨组织ENaCα、ClC-3蛋白表达水平下降(P<0.05),NCC蛋白表达水平升高(P<0.05),补肾中药复方干预后能够不同程度的调节高盐引起的相关离子通道的表达。结论:补肾中药复方能够不同程度的调节高盐引起的相关离子通道ENaCα、ClC-3、NCC的表达,对骨代谢失衡具有一定的改善和治疗作用。AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respectively.The dose of BHF was 7.8 g·kg^(-1)·d^(-1),once a day,and the treatment lasted for 12 weeks.Bone density,bone microarchitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channelα(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type I procollagen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone resorption markers,such as amino-terminal cross-linked telopeptides of type I collagen(NTX),carboxy-terminal crosslinked telopeptides of type I collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly increased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expression levels of ENaCαand ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion ch

关 键 词：高盐摄入 骨代谢 离子通道 补肾中药复方 

分 类 号：R363.2[医药卫生—病理学] R246.1[医药卫生—基础医学]