超声应变技术评估PCSK9基因敲除对肥胖小鼠心肌功能的影响  

Effect of PCSK9 Gene Knockout on Myocardial Function in Obese Mice via Ultrasound Strain

作　　者：王琴 井一淑 马鑫 潘璐 燕茹[3] 马学平 WANG Qin;JING Yishu;MA Xin;PAN Lu;YAN Ru;MA Xueping(Department of Cardiology,General Hospital of Ningxia Medical University,Yinchuan 750004,China;不详)

机构地区：[1]宁夏医科大学总医院心脏中心功能检查部,宁夏银川750004 [2]延安市人民医院超声诊断科,陕西延安716000 [3]宁夏医科大学总医院心内科,宁夏银川750004

出　　处：《中国医学影像学杂志》2024年第9期873-877,907,共6页Chinese Journal of Medical Imaging

基　　金：宁夏自然科学基金(2023AAC02060,2023AAC03637,2022AAC03481,2021AAC03320)。

摘　　要：目的应用超声应变技术评估PCSK9基因敲除对肥胖小鼠心肌功能的影响,并探讨其机制。材料与方法选取6周龄野生型C57BL/6雄性小鼠20只,随机分为正常组和肥胖组,各10只;选取6周龄PCSK9^(-/-)C57BL/6雄性小鼠10只为PCSK9^(-/-)组。肥胖组和PCSK9^(-/-)组给予高脂饲料造模,正常组给予普通饲料,12周后从肥胖组和PCSK9^(-/-)组中选取造模成功小鼠,3组小鼠行心脏超声、透射电镜及免疫荧光染色进行观察。结果肥胖组、正常组和PCSK9^(-/-)组小鼠室间隔舒张末期厚度分别为(0.98±0.13)mm、(0.77±0.07)mm、(0.78±0.13)mm,差异有统计学意义(F=5.10,P=0.02),肥胖组较正常组增厚(t=2.73,P<0.05),PCSK9^(-/-)组较肥胖组变薄(t=-2.92,P<0.05)。3组左心室整体纵向应变及整体圆周应变差异有统计学意义(F=7.44、15.40,P<0.05),其中肥胖组较正常组整体纵向应变和整体圆周应变减低(t=3.79、5.50,P<0.05),PCSK9^(-/-)组较肥胖组整体纵向应变和整体圆周应变升高(t=-2.53、-3.37,P<0.05)。电镜及免疫荧光结果显示,肥胖组心肌超微结构受损,NLRP3及Caspase-1表达较正常组增多(t=12.53、-4.73,P<0.05),PCSK9^(-/-)组心肌超微结构受损明显改善,NLRP3及Caspase-1表达较肥胖组减少(t=-6.23、2.05,P<0.05)。结论超声应变技术较常规心脏超声参数能更敏感地发现PCSK9基因敲除肥胖小鼠心肌功能的改变;PCSK9基因敲除后可能通过抑制NLRP3及Caspase-1表达改善肥胖小鼠心肌功能。Purpose To evaluate the effect of PCSK9 gene knockout on myocardial function in obese mice via ultrasound strain technology,and to discuss the related mechanisms.Materials and Methods Twenty six-week-old wild-type C57BL/6 male mice were selected and randomly divided into a normal group(n=10)and an obese group(n=10).Additionally,ten six-week-old PCSK9^(-/-)C57BL/6male mice were selected as the PCSK9^(-/-)group.Mice in the obese group and PCSK9^(-/-)group were fed with high-fat feed to create models,while those in the normal group were fed with regular feed.After 12 weeks,mice that were successfully modeled were selected from the obese group and PCSK9^(-/-)group.Then,the three groups of mice were subjected to cardiac ultrasound,transmission electron microscopy and immunofluorescence staining to observe relevant indicators.Results The interventricular septal end-diastolic thickness of mice in obese group,normal group,and PCSK9^(-/-)group were(0.98±0.13)mm,(0.77±0.07)mm,(0.78±0.13)mm,respectively,with statistically significant difference(F=5.10,P=0.02).The obese group was thicker than the normal group(t=2.73,P<0.05),while the PCSK9^(-/-)group was thinner than the obese group(t=-2.92,P<0.05).There were statistically significant differences in global longitudinal strain and global circumferential strain of the left ventricle among the three groups(F=7.44,15.40,P<0.05),with the obese group showing a decrease in global longitudinal strain and global circumferential strain compared to the normal group(t=3.79,5.50,P<0.05).The PCSK9^(-/-)group showed an increase in global longitudinal strain and global circumferential strain compared to the obese group(t=-2.53,-3.37,P<0.05).Electron microscopy and immunofluorescence results showed that the myocardial ultrastructure of the obese group was damaged,and the expression of NLRP3 and Caspase-1 were higher than that of the normal group(t=12.53,-4.73,P<0.05),the myocardial ultrastructure damage in the PCSK9^(-/-)group was significantly improved,the expression of NLRP3 and Caspase

关 键 词：肥胖症 超声检查 心脏 应变 显微镜检查 电子 透射 PCSK9基因 基因敲除技术 心肌功能 小鼠 

分 类 号：R445.1[医药卫生—影像医学与核医学] R-33[医药卫生—诊断学] R542.2[医药卫生—临床医学]