中华骨质疏松和骨矿盐疾病杂志2024，Vol.17Issue(2)：114-122,9.DOI:10.3969/j.issn.1674-2591.2024.02.003
Pls3突变相关新型早发骨质疏松大鼠模型的心血管改变及机制
Cardiovascular changes and its mechanism in a novel rat model of early-onset osteoporosis induced by Pls3 mutation
摘要
Abstract
Objective To evaluate the cardiovascular phenotype and its relationship to collagen metabolism in a novel rat model of early-onset osteoporosis(EOOP)induced by Pls3 mutation.Methods Comparison of cardiac pheno-type was completed between rats with knockout of the 10-16 exons of Pls3(Pls3E10-16del/0)constructed by CRISPR/Cas9 technology and wild type rats.Immunohistochemical staining was used to evaluate the expression of PLS3 in cardiovascular tissues.Echocardiography was used to assess cardiovascular morphology and function.H&E staining was used to evaluate the histological change of myocardial tissue.The collagen microstructure and arrangement were evaluated by scanning elec-tron microscopy.Results In the cytoplasm of the cardiovascular tissues,PLS3 was widely expressed in wild-type rats,and significantly decreased in Pls3E10-16del/0 rats.At 6-8 weeks of age,no significant structural and functional abnormalities were observed in the heart and great vessels of Pls3E10-16del/0 rats.However,compared with wild-type rats,Pls3E10-16del/0 rats showed reductions in right ventricular end-diastolic diameter and proximal ascending aorta diameter.In Pls3E10-16del/0 rats,collagen synthesis in cardiovascular tissues was not affected,but electron microscopy showed that fine collagen fibers were broken and disorganized in the heart and ascending aorta.Conclusion We firstly evaluated the cardiovascular phenotype of a new Pls3E10-16del/0 rat model with EOOP,which had decreased internal diameter of the right ventricle and ascending aorta,broken and scattered fine collagen fibers.The effects of mutation in Pls3 on the cardiovascular system need to be observed for a long time.This study expands the understanding of the cardiovascular phenotype of rare Pls3-associated ear-ly-onset osteoporosis.关键词
早发骨质疏松症/Pls3基因突变/心血管表型Key words
early-onset osteoporosis/Pls3 gene mutation/cardiovascular phenotypes分类
医药卫生引用本文复制引用
周冰娜,赵笛辰,胡静,张茜,王鸥,夏维波,邢小平,陈太波,李梅..Pls3突变相关新型早发骨质疏松大鼠模型的心血管改变及机制[J].中华骨质疏松和骨矿盐疾病杂志,2024,17(2):114-122,9.基金项目
国家重点研发计划(2021YFC2501700) （2021YFC2501700）
国家自然科学基金面上项目(82070908,82370894) （82070908,82370894）
中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-051) （2021-I2M-1-051）
中央高水平医院临床研究专项(2022-PUMCH-B-014) （2022-PUMCH-B-014）
