SHJH^(hr)小鼠的心脏衰老表型研究  

Study on Cardiac Aging Phenotypes of SHJH^(hr)Mice

作　　者：刘荣乐 程灏 尚付生 常书福[1] 徐平 LIU Rongle;CHENG Hao;SHANG Fusheng;CHANG Shufu;XU Ping(Zhongshan Hospital,Fudan University,Shanghai 200032,China;Institute of Translational Medicine,Shanghai University,Shanghai 200444,China;Shanghai Jihui Laboratory Animal Care Co.,Ltd.,Shanghai 201611,China)

机构地区：[1]复旦大学附属中山医院,上海200032 [2]上海大学转化医学研究院,上海200444 [3]上海吉辉实验动物饲养有限公司,上海201611

出　　处：《实验动物与比较医学》2025年第1期13-20,共8页Laboratory Animal and Comparative Medicine

基　　金：上海市科技创新行动计划项目“自发性早衰老小鼠的心血管衰老相关表型分析及机制研究”(21140900103)。

摘　　要：目的探讨自发性早衰SHJH^(hr)小鼠心脏的衰老现象。方法对不同周龄(10周龄和24周龄)的SHJH^(hr)小鼠(SHJH^(hr)组)和野生型ICR小鼠[用作野生组(wild-type,WT组)]进行对比研究。用小动物活体超声影像系统分析心脏功能,安死术后采集各脏器并称重,了解心脏萎缩情况;苏木精-伊红(hematoxylin-eosin,HE)染色后观察心脏病理损伤情况;Masson染色后分析心脏纤维化情况;麦胚凝集素(wheat-germ agglutinin,WGA)染色后分析心脏心肌细胞面积;酶联免疫吸附法检测心肌组织中氧化损伤指标包括超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GPX)和过氧化氢酶(catalase,CAT)的活性以及8-羟基-2'-脱氧鸟苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)含量;实时荧光定量PCR法检测炎症、纤维化、氧化应激相关标志因子的mRNA表达水平;比色法检测丙二醛(malondialdehyde,MDA)水平。结果与同周龄的WT组小鼠相比,10周龄SHJH^(hr)组小鼠的每搏输出量(stroke volume,SV)、射血分数(ejection fraction,EF)、缩短分数(fractional shortening,FS)和心肺重量无明显差异;但是当小鼠达到24周龄时,SHJH^(hr)组小鼠的SV、EF和FS值明显低于同周龄WT组小鼠(均P<0.05),肺脏重量无显著变化,但是心脏重量显著降低(P<0.05)。选取24周龄小鼠心脏组织进行组织学分析发现:与WT组小鼠相比,SHJH^(hr)组小鼠的心脏纤维化水平无明显差异,但WGA染色显示心肌细胞面积显著减少(P<0.05)。PCR检测发现氧化应激标志因子Sod2、Gpx1和Cat基因的mRNA水平显著下调(均P<0.05)。生化检测发现心肌组织中氧化损伤相关酶SOD、GPX和CAT活性显著降低(均P<0.05),而氧化应激标志物8-OHdG和MDA水平显著增加(均P<0.05)。结论SHJH^(hr)小鼠心脏出现早衰现象,可能与心肌组织氧化应激损伤有关。Objective To investigate the spontaneous premature cardiac aging in SHJH^(hr)mice.Methods A comparative study was conducted between SHJH^(hr)mice(SHJH^(hr)group)and wild-type ICR mice(WT group)at different ages(10 and 24 weeks).Cardiac function was analyzed using a small animal in vivo ultrasound imaging system.After euthanasia,organs were collected and weighed to assess the extent of cardiac atrophy.Cardiac pathological damage was observed using hematoxylin-eosin(HE)staining.Cardiac fibrosis was analyzed using Masson staining.Myocardial cell area was analyzed after wheat germ agglutinin(WGA)staining.The activities of oxidative damage indicators in myocardial tissue,including superoxide dismutase(SOD),glutathione peroxidase(GPX),and catalase(CAT),as well as the content of 8-hydroxy-2'-deoxyguanosine(8-OHdG),were measured using enzyme-linked immunosorbent assay.Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation,fibrosis,and oxidative stress.Colorimetric assay was used to measure malondialdehyde(MDA)levels.Results Compared to WT group mice of the same age,10-week-old mice in the SHJH^(hr)group showed no significant differences in stroke volume(SV),ejection fraction(EF),fractional shortening(FS),or heart and lung weights.However,at 24 weeks of age,mice in the SHJH^(hr)group had significantly lower SV,EF,and FS values compared to mice of the same age in the WT group(P<0.05),with no significant change in lung weight but a significant reduction in heart weight(P<0.05).Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJH^(hr)and WT groups,but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJH^(hr)group(P<0.05).PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2,Gpx1,and Cat genes(P<0.05).Biochemical assays indicated significantly reduced activities of oxidative damage-related enzyme

关 键 词：SHJH^(hr)小鼠 心脏衰老 氧化损伤 

分 类 号：R-332[医药卫生] Q95-33[生物学—动物学]