血管紧张素Ⅱ微量泵植入和皮下注射致小鼠心肌纤维化的造模方法比较  

Comparison of two modeling methods In mice myocardial fibrosis model inducedby micropump and subcutaneous injection of AngⅡ

作　　者：潘亮亮 张思涵 王雪晴 杨晓薇 王少兰[1] 李汨 马晓真 于远望[1] PAN Liangliang;ZHANG Sihan;WANG Xueqing;YANG Xiaowei;WANG Shaolan;LI Mi;MA Xiaozhen;YU Yuanwang(Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学基础医学院,陕西咸阳712046 [2]西藏民族大学医学院,陕西咸阳712082

出　　处：《陕西医学杂志》2025年第1期14-20,共7页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81904038);陕西省教育厅重点科学研究计划项目(23JS009,22JS004);陕西省中西医结合心血管病防治重点实验室项目(303-1730202030)。

摘　　要：目的:比较血管紧张素Ⅱ(AngⅡ)微量泵植入和皮下注射两种造模方式及不同剂量致小鼠心肌纤维化的成模情况及成模差异性,确定较优的动物模型复制方法。方法:40只雄性C57BL/6小鼠随机分为空白对照组、微量泵组[微量泵皮下植入1.5 mg/(kg·d)]、皮下组1[皮下注射1.5 mg/(kg·d)]和皮下组2[皮下注射2.5 mg/(kg·d)],每组10只,空白组不做任何处理,其余组给予AngⅡ,持续28 d,观察小鼠一般状态。第28天行心电图和超声心动图检测心功能,HE、Masson染色观察心脏病理变化,ELISA检测血清脑钠肽(BNP)水平,Western blot检测心肌α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(CollagenⅠ)、Ⅲ型胶原蛋白(CollagenⅢ)蛋白表达。结果:同空白对照组比较,各给药组小鼠一般状态、心电图受影响程度为微量泵组>皮下组2>皮下组1。超声心动图微量泵组和皮下组2的左室射血分数(EF)、左室短轴缩短率(FS)下降(均P<0.05),左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、左室舒张末期容量(LVEDV)、左室收缩末期容量(LVESV)、左室质量(LVd Mass)均上升(均P<0.05);皮下组1的FS下降(P<0.05),LVIDs、LVIDd上升(均P<0.05),各组间EF比较有统计学差异(均P<0.05)。微量泵组和皮下组2的BNP均显著升高(P<0.05),皮下组1与空白对照组比较无统计学差异,各给药组间比较差异有统计学意义(P<0.05)。HE染色微量泵组炎性细胞浸润明显大于皮下组,Masson染色胶原纤维沉积高于皮下组2(均P<0.05),皮下组1与空白对照组比较无统计学差异(P>0.05)。Western blot微量泵组和皮下组2的α-SMA、CollagenⅠ、CollagenⅢ蛋白表达显著增高(均P<0.05),皮下组1仅α-SMA增高(P<0.05)。结论:微量泵1.5 mg/(kg·d)和皮下注射2.5 mg/(kg·d)累积28 d均可建立心肌纤维化模型,微量泵组明显优于皮下注射;皮下注射1.5 mg/(kg·d)诱导心肌纤维化不明显。Objective:To compare the modelling methods of micropump implantation and subantaneous injection of AngiotensinⅡ(AngⅡ),as well as the differences myocardial fibrosis induced by different doses in mice,and the optimal replication method of animal models was determined.Methods:Forty male C57BL/6 mice were randomly divided into blank control group,micropump group[micropump subcutaneous implantation of 1.5 mg/(kg·d)],subcutaneous group 1[subcutaneous injection of 1.5 mg/(kg·d)]and subcutaneous group 2[subcutaneous injection of 2.5 mg/(kg·d)],each group of 10,the blank group did not do any treatment,and the rest of the group was given AngⅡfor 28 days,and the general state of the mice was observed.On the 28th day,electrocardiogram and echocardiography were performed to detect cardiac function,HE and Masson staining were used to observe the changes in cardiac theory,serum BNP levels were detected by ELISA,and myocardialα-SMA,CollagenⅠ,and CollagenⅢ.protein expressions were detected by Western blot.Results:Compared with the blank control group,the general state and electrocardiogram of mice in each administration group were the micropump group>the subcutaneous group>the subcutaneous group 1.The left ventricular ejection fraction(EF)and left ventricular short-axis shortening rate(FS)decreased in the echocardiographic micropump group and subcutaneousgroup 2(all P<0.01),and the left ventricular end-diastolic internal diameter(LVIDd),left ventricular end-systolic diameter(LVIDs),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),and left ventricular mass(LVd mass)increased(all P<0.05).In subcutaneous group 1,FS decreased(P<0.05),LVIDs and LVIDd increased(P<0.05),and EF was different among groups(P<0.01).The serum natriuretic peptide(BNP)in the micropump group and subcutaneous group 2 was significantly increased(P<0.05),and there was no significant difference between the subcutaneous group 1 and the blank control group,and the difference between the administration groups was

关 键 词：血管紧张素Ⅱ 心肌纤维化 造模方法 微量泵植入 皮下注射 动物模型 

分 类 号：R542.2[医药卫生—心血管疾病]