Egr3基因敲除对动脉粥样硬化小鼠主动脉组织炎症及细胞凋亡的影响  

Effect of Egr3 gene knockout on inflammation and apoptosis in aortic tissues of atherosclerotic mice

作　　者：李娇 祖姆热提·阿布都克依木 王思晴 刘芳[1] 吴宇轩 李霞[1] LI Jiao;Zumureti ABUDUKEYIMU;WANG Siqing;LIU Fang;WU Yuxuan;LI Xia(Department of General Medicine,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang Uygur Autonomous Region 830000,China)

机构地区：[1]新疆医科大学第五附属医院全科医学科,新疆维吾尔自治区乌鲁木齐830000

出　　处：《中华实用诊断与治疗杂志》2025年第2期97-104,共8页Journal of Chinese Practical Diagnosis and Therapy

基　　金：“天山英才”医药卫生高层次人才培养计划(TSYC202301B015);国家自然科学基金(81960073);新疆维吾尔自治区研究生科研创新项目(XJ2024G165)。

摘　　要：目的 构建早期生长反应因子3(Egr3)基因敲除动脉粥样硬化小鼠模型,探讨Egr3对主动脉组织炎症及细胞凋亡的影响。方法 SPF级雄性Egr3^(fl/fl)和Egr3^((fl/fl, Cdh5-cre))小鼠各16只,体质量16.2~23.5 g,将Egr3^(fl/fl)小鼠分为对照组(常规饲料喂养12周)、模型组(注射PCSK9腺相关病毒载体AAV8-PCSK9并高脂饲料喂养12周构建动脉粥样硬化模型)各8只,将Egr3^((fl/fl, Cdh5-cre))小鼠分为Egr3^(-/-)组(他莫昔芬注射诱导Egr3基因敲除并常规饲料喂养12周)、Egr3^(-/-)+模型组(他莫昔芬注射诱导Egr3基因敲除后注射AAV8-PCSK9并高脂饲料喂养12周构建动脉粥样硬化模型)各8只。4组小鼠饲料喂养期间每周称体质量,造模2、4、8、12周时采用生化试剂盒检测血糖、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平。造模12周时采用HE染色观察主动脉组织病理情况,采用油红O染色观察主动脉斑块形成情况并计算主动脉斑块面积百分比,采用TUNEL法检测主动脉组织细胞凋亡情况,采用ELISA法检测血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,采用Western blot法检测主动脉组织Egr3、Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤-2(Bcl-2)蛋白相对表达量。结果 随造模时间延长,4组体质量有逐渐增高趋势。造模2、4、8周时对照组、Egr3^(-/-)组血糖、TC、TG、LDL-C、HDL-C水平均无明显变化;模型组、Egr3^(-/-)+模型组血糖、TC、TG、LDL-C水平均逐渐升高,HDL-C水平均逐渐降低。造模12周时4组体质量、血糖、TC、TG、LDL-C、HDL-C水平比较差异均有统计学意义(F=5.867~185.639,P均<0.05)。模型组、Egr3^(-/-)+模型组体质量均高于对照组(P<0.05),Egr3^(-/-)+模型组高于Egr3^(-/-)组(P<0.05);模型组、Egr3^(-/-)+模型组血糖、TC、TG、LDL-C水平均高于对照组、Egr3^(-/-)组(P<0.05),HDL-C水平均低于对照组、Egr3^(-/-)组(P<0.05);模型组血糖、TC�Objective To construct the early growth response factor 3(Egr3)gene knockout mice models of atherosclerosis,and to explore the effect of Egr3 on inflammation and apoptosis in aortic tissues.Methods Sixteen SPF-grade male Egr3^(fl/fl) mice and 16 Egr3^((fl/fl, Cdh5-cre))mice weighing 16.2-23.5 g were enrolled.The Egr3/fl mice were equally divided into the control group(fed with regular diet for 12 weeks)and the model group(injected with PCSK9 adeno-associated virus vector AAV8-PCSK9 and fed with high-fat diet for 12 weeks to induce atherosclerosis model),and the Egr3^((fl/fl, Cdh5-cre)) mice were equally divided into the Egr3^(-/-)g group(induced by tamoxifen injection for Egr3 gene knockout and fed with regular diet for 12 weeks)and the Egr3^(-/-)+model group(induced by tamoxifen injection for Egr3 gene knockout,followed by injection of AAV8-PCSK9 and fed with high-fat diet for 12 weeks to induce atherosclerosis model).The body mass was measured weekly during the feeding period in these four groups.At 2,4,8 and 12 weeks of modeling,biochemical kits were used to detect the levels of blood glucose,total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).At 12 weeks of modeling,HE staining was used to observe the histopathology in aortic tissues,oil red O staining was used to observe the aortic plaque formation and calculate the aortic plaque area percentage,TUNEL assay was used to detect the apoptosis in aortic tissues,ELISA was used to detect serum levels of interleukin-1β(IL-1p)and tumor necrosis factor-α(TNF-α),and Western blot was used to detect the relative expressions of Egr3,Bcl-2 associated X protein(Bax)and B-cell lymphoma-2(Bcl-2)proteins in aortic tissues.Results As the modeling time prolonged,there was a gradual increasing trend in body mass in the four groups.At 2,4 and 8 weeks of modeling,the blood glucose,TC,TG,LDL-C and HDL-C levels showed no significant changes in the control group and Egr3^(-/-)group;the blood glucose,T

关 键 词：动脉粥样硬化 早期生长反应因子3 炎症 细胞凋亡 条件性基因敲除 小鼠 

分 类 号：R54[医药卫生—心血管疾病]