ACE2/Ang(1-7)/Mas轴对尿毒症大鼠高转化骨病的改善作用  

Ameliorative effect of ACE2/Ang(1-7)/Mas axis on high-turover bone disease in uremic rats

作　　者：薛杨[1] 阮颖新[1] 闫铁昆[1] 贾俊亚[1] 林珊[1] XUE Yang;RUAN Yingxin;YAN Tiekun;JIA Junya;LIN Shan(Department of Nephrology,First Affiliated Hospital,Tianjin Medical University,Tianjin 300054,China)

机构地区：[1]天津医科大学总医院肾内科,天津300054

出　　处：《吉林大学学报(医学版)》2025年第1期26-33,共8页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金青年基金项目(82000669);国家自然科学基金面上基金项目(81570630);天津市医学重点学科(专科)建设项目(TJYXDXK-071C);天津市卫健委科技项目(ZC20219)。

摘　　要：目的:探讨血管紧张素(1-7)[Ang(1-7)]对大鼠尿毒症高转性骨病的影响,并阐明其可能的机制。方法:30只SD大鼠随机分为假手术组(n=6)和实验组(n=24),实验组大鼠采用5/6肾切除术(Platt法)+高磷(P)饮食[1.2%P,1.0%钙(Ca)]制备尿毒症高转化骨病模型,并将建模成功的大鼠随机分为模型组、Ang(1-7)组、血管紧张素转换酶2(ACE2)激活剂二乙酰胺三氮脒(DIZE)组(DIZE组)和Mas受体拮抗剂组(A779组),每组6只。分别于手术后12和18周采用全自动生化分析仪检测各组大鼠血清Ca、P、血肌酐(Scr)、血尿素氮(BUN)和24 h尿蛋白(UP)水平;免疫化学荧光法测定各组大鼠全段甲状旁腺素(iPTH)水平;酶联免疫吸附试验(ELISA)法检测各组大鼠血清骨钙素(OC)、Ⅰ型胶原N端肽(NTX)和抗酒石酸酸性磷酸酶(TRAP)-5b水平;高分辨率显微CT扫描检测各组大鼠股骨组织的骨密度(BMD)、组织骨密度(TMD)、骨小梁厚度(Tb.Th)和骨小梁分离度(Tb.Sp)等三维结构参数。Von Kossa染色和吉姆萨染色观察各组大鼠皮质骨及骨小梁病理形态表现,计算骨小梁体积(TBV);荧光显微镜下测定各组大鼠骨矿化率(MAR),并计算成骨细胞指数(OBI)和破骨细胞指数(OCI)。结果:术后12和18周,与假手术组比较,模型组、Ang(1-7)组、DIZE组和A779组大鼠体质量减小(P<0.05);术后12和18周,与假手术组比较,模型组、Ang(1-7)组、DIZE组和A779组大鼠血清中24 h UP、Scr及BUN水平均升高(P<0.05);术后18周,与模型组比较,Ang(1-7)组和DIZE组大鼠血清中24 h UP及Scr水平均降低(P<0.05),A779组大鼠血清中24 h UP、Scr和BUN水平均升高(P<0.05)。证实尿毒症高转化骨病大鼠模型构建成功。术后12和18周,与假手术组比较,模型组、Ang(1-7)组、DIZE组和A779组大鼠血清中iPTH、P、OC、NTX及TRAP-5b水平均升高(P<0.05);术后18周,与模型组比较,Ang(1-7)组和DIZE组大鼠血清中NTX及TRAP-5b水平均降低(P<0.05),A779组大鼠血清中iPTH、P、NTX和Objective:To discuss the effect of angiotensin(1-7)[Ang(1-7)]on high-turnover bone disease in the uremic rats,and to clarify its possible mechanism.Methods:Thirty SD rats were randomly divided into sham operation group(n=6)and experimental group(n=24).The rats in experimental group underwent 5/6 nephrectomy(Platt method)+high-phosphorus(P)diet[1.2%P,1.0%calcium(Ca)]to establish the model of uremic high-turnover bone disease.The successfully modeled rats were then randomly divided into model group,Ang(1-7)group,angiotensin-converting enzyme 2(ACE2)activator dimethylacetamide amidoxime(DIZE)group,and Mas receptor antagonist group(A779 group),with 6 rats in each group.The levels of Ca,P,blood creatinine(Scr),blood urea nitrogen(BUN),and 24 h urinary protein(UP)in serum of the rats in various groups were detected by automatic biochemical analyzer at 12 and 18 weeks after operation;immunofluorescence staining was used to detect the levels of intact parathyroid hormone(iPTH)in the rats in various groups;ELISA method was used to detect the levels of osteocalcin(OC),typeⅠcollagen N-terminal peptide(NTX),and tartrate-resistant acid phosphatase(TRAP)-5b in serum of the rats in various groups;high-resolution micro-CT scan was used to detect the bone density(BMD),tissue mineral density(TMD),trabecular thickness(Tb.Th),and trabecular separation(Tb.Sp)in femur tissue of the rats in various groups;Von Kossa staining and Giemsa staining were used to observe the pathomorphology of cortical bone and trabecular bone of the rats in various groups,and the trabecular bone volume(TBV)was calculated;fluorescence microscope was used to detect the mineral apposition rates(MAR)of the rats in vanious groups,and the osteoblast index(OBI)and osteoclast index(OCI)of the rats in various groups were calculated.Results:At 12 and 18 weeks after operation,compared with sham operation group,the weights of the rats in model group,Ang(1-7)group,DIZE group,and A779 group were decreased(P<0.05).At 12 and 18 weeks after operation,compared with sham ope

关 键 词：尿毒症 高转化骨病 成骨细胞 破骨细胞 血管紧张素转换酶2 血管紧张素(1-7) 

分 类 号：R563.13[医药卫生—呼吸系统]