HSF1基因敲除小鼠心脏老化淀粉样变模型建立与检测  

Establishment and characterization of Hsf1 gene knockout cardiac amyloidosis mouse model

作　　者：袁潘攀 陈诗琦 杨亚儒 王艳军[1] 李瑞琛 钱俊乔[2] 霍佳[3] 李陈莉[4,5] 钱金泽 Yuan Panpan;Chen Shiqi;Yang Yaru;Wang Yanjun;Li Ruichen;Qian Junqiao;Huo Jia;Li Chenli;Qian Jinze(Hebei Key Laboratory of Nephrology,Department of Pathology,Hebei Medical University,Shijiazhuang 050017,China;Department of Oral Surgery,Stomatology Hospital,Hebei Medical University,Shijiazhuang 050000,China;Department of Orthopedics,Third Affiliated Hospital of Hebei Medical University,Shijiazhuang 050000,China,4.Department of Histology and Embryology,Hebei Medical University,Shijiazhuang 050017,China,5.Department of clinical medicine,Shijiazhuang Medical College,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学病理学教研室河北省肾脏病重点实验室 [2]河北医科大学口腔医院口外科 [3]河北医科大学附属第三医院骨病科 [4]河北医科大学组织学与胚胎学教研室 [5]石家庄医学高等专科学校临床医学系

出　　处：《中国组织化学与细胞化学杂志》2018年第2期135-140,共6页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金青年基金项目(81300606);河北省高等学校科学技术研究项目(BJ2014042);高等学校博士科学点专项科研基金(2012323120012);河北省卫生厅医学科学研究课题计划项目(ZD20140355)

摘　　要：目的探讨小鼠心脏淀粉样变疾病模型的建立以及淀粉样纤维在小鼠心脏组织中的形态学观察。方法采用雌性热休克转录因子1(heat shock factor 1,HSF1)基因敲除(Hsf1^(-/-))小鼠和野生型ICR小鼠进行淀粉样变诱导实验,构建老化淀粉样变疾病模型。模型构建2个月后,通过刚果红染色、免疫组织化学、电镜等方法对各个实验组心脏组织中淀粉样变沉积情况及心功能进行评估。结果通过淀粉样变诱导实验2个月后,Hsf1^(-/-)小鼠与野生型小鼠各组织中均有淀粉样物质沉积,但心脏组织中淀粉样纤维沉积程度显著不同,且沉积部位主要位于小鼠心肌中的结缔组织内及小血管的管壁,并引起心肌细胞损伤。此外,Hsf1^(-/-)小鼠心脏淀粉样变程度显著高于野生型小鼠,心功能损伤程度显著高于野生型小鼠。结论 Hsf1基因敲除小鼠可用于构建心脏淀粉样变疾病的动物模型,并应用于心脏淀粉样变疾病的基础及临床研究。Objective To establish and characterize a cardiac amyloidosis mouse model. Methods In this study, senile systemic amyloidosis was induced through injecting amyloid fibrils into female Hsf1^（-/-）knockout mice or wide type mice. Two months after the injection, tissue amyloid deposition and cardiac functions were assessed in experimental mice by Congo red staining, immunohistochemistry and transmission electron microscopy. Results Two months after amyloidosis induction, the levels of tissue amyloid deposits were similar between Hsf1^（-/-）and wild-type mice, except in heart where Hsf1^（-/-）showed significantly higher level of deposition. Cardiac amyloids mainly deposited in the connective tissue and small vessel wall of myocardium, the extend of which correlated with cardiac hypertrophy and contractile dysfunction. Furthermore, Hsf1^（-/-）knockout mice exhibited increased cardiac AApo AII deposition. Conclusion These results suggested that Hsf1^（-/-）knockout mice could be used as a senile cardiac amyloidosis model for relevant study.

关 键 词：淀粉样纤维 心肌 老化 小鼠模型 

分 类 号：R361.1[医药卫生—病理学]