吉林大学学报（医学版）2025，Vol.51Issue(1)：26-33,8.DOI:10.13481/j.1671-587X.20250104
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
摘要
Abstract
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),type Ⅰ collagen 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 operation group,the levels of 24 h UP,Scr,and BUN in serum of the rats in model group,Ang(1-7)group,DIZE group,and A779 group were increased(P＜0.05);at 18 weeks after operation,compared with model group,the levels of 24 h UP and Scr in serum of the rats in Ang(1-7)group and DIZZ group were decreased(P＜0.05),and the levels of 24 h UP,Scr and BUN in serum of the rats in A779 group were increased(P＜0.05).The successful establishment of the uremic high-turnover bone disease model was confirmed.At 12 and 18 weeks after operation,compared with sham operation group,the serum iPTH,P,OC,NTX,and TRAP-5b levels ofthe rats in model group,Ang(1-7)group,DIZE group,and A779 group were all significantly increased(P＜0.05);at 18 weeks after operation,compared with model group,the serum NTX and TRAP-5b levels of the rats in Ang(1-7)group and DIZE group were decreased(P＜0.05),while the serum iPTH,P,NTX and TRAP-5b levels in A779 group were increased(P＜0.05).The high-resolution micro-CT scan results showed that compared with sham operation group,the values of femur BMD and TMD of the rats in model group,Ang(1-7)group,DIZE group,and A779 group were all significantly decreased(P＜0.05);compared with model group,the values of femur BMD and TMD of the rats in Ang(1-7)group and DIZE group were increased(P＜0.05),while the values of BMD and TMD of the rats in A779 group were decreased(P＜0.05).Compared with sham operation group,the femur Tb.Th of the rats in model group was decreased(P＜0.05),and the Tb.Sp was increased(P＜0.05);the femur Tb.Th of the rats in Ang(1-7)group and DIZE group were increased(P＜0.05),and the Tb.Sp was decreased(P＜0.05).Compared with model group,the femur Tb.Th of the rats in A779 group was decreased(P＜0.05),and the Tb.Sp was increased(P＜0.05).The bone pathological examination results showed that compared with sham operation group,the femur TBV of the rats in model group,Ang(1-7)group,DIZZ group and A779 group were decreased(P＜0.05),and MAR,OBI and OCI were increased(P＜0.05);compared with model group,the OBI and OCI of the rats in Ang(1-7)group and DIZE group were decreased(P＜0.05),and TBV was increased(P＜0.05),while the OBI and OCI of the rats in A779 group were increased(P＜0.05),and TBV was decreased(P＜0.05).Conclusion:The ACE2/Ang(1-7)/Mas axis improves high-turnover bone disease in the uremic rats.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)Key words
Uremia/High-turnover bone disease/Osteoblasts/Osteoclasts/Angiotensin-converting enzyme 2/Angiotensin(1-7)分类
临床医学引用本文复制引用
薛杨,阮颖新,闫铁昆,贾俊亚,林珊..ACE2/Ang(1-7)/Mas轴对尿毒症大鼠高转化骨病的改善作用[J].吉林大学学报（医学版）,2025,51(1):26-33,8.基金项目
国家自然科学基金青年基金项目(82000669) （82000669）
国家自然科学基金面上基金项目(81570630) （81570630）
天津市医学重点学科(专科)建设项目(TJYXDXK-071C) （专科）
天津市卫健委科技项目(ZC20219) （ZC20219）
