[1]安丽伟,韩娇娇,谢阳阳,等.Caspase-8/GSDME通路调控巨噬细胞焦亡在心肌梗死大鼠模型中的机制研究[J].现代检验医学杂志,2025,40(06):165-170.[doi:10.3969/j.issn.1671-7414.2025.06.030]
　AN Liwei,HAN Jiaojiao,XIE Yangyang,et al.Mechanism of Macrophage Pyroptosis Regulated by Caspase-8/GSDME Pathway in Rat Model of Myocardial Infarction[J].Journal of Modern Laboratory Medicine,2025,40(06):165-170.[doi:10.3969/j.issn.1671-7414.2025.06.030]
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Caspase-8/GSDME通路调控巨噬细胞焦亡在心肌梗死大鼠模型中的机制研究()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年06期
页码:
165-170
栏目:
论著
出版日期:
2025-11-15

文章信息/Info

Title:
Mechanism of Macrophage Pyroptosis Regulated by Caspase-8/GSDME Pathway in Rat Model of Myocardial Infarction
文章编号:
1671-7414（2025）06-165-06
作者:
安丽伟1a，韩娇娇1a，谢阳阳1b，王 彬2a，王 锦2b，张丽军3
1.定州市人民医院 a.心内科；b.血液科，河北定州 073000；2.永清县人民医院 a.内三科; b.急诊科，河北廊坊 065600；3.石家庄市第三医院肿瘤血液科，石家庄 050011
Author(s):
AN Liwei1a, HAN Jiaojiao1a, XIE Yangyang1b, WANG Bin2a, WANG Jin2b, ZHANG Lijun3
1a.Department of Cardiology;1b.Department of Hematology, People’s Hospital of Dingzhou, Hebei Dingzhou 073000 , China; 2a.Department of Internal Medicine; 2b.Department of Emergency, People’s Hospital of Yongqing County, Hebei Langfang 065600 , China; 3.D
关键词:
心肌梗死; 巨噬细胞; 半胱氨酸天冬氨酸蛋白酶8/消皮素E通路; 细胞焦亡
分类号:
R-332
DOI:
10.3969/j.issn.1671-7414.2025.06.030
文献标志码:
A
摘要:
目的探究半胱氨酸天冬氨酸蛋白酶8（Caspase-8）/消皮素E（GSDME）通路调控巨噬细胞焦亡在心肌梗死（MI）大鼠模型中的作用及可能机制。方法将30只大鼠随机分为假手术组、MI组及Caspase-8抑制（Z-IETD-FMK）组，每组10只。培养大鼠巨噬细胞RMa-bm分为对照组、缺氧组及Z-IETD-FMK组。H&E染色检测心肌组织病理变化。马松（Masson）染色检测心肌组织纤维化水平。RT-qPCR及Westernblotting检测心肌组织中Caspase-8，GSDME以及巨噬细胞中Caspase-8，GSDME，NLR家族Pyrin域蛋白3（NLRP3），含有CARD的凋亡相关斑点样蛋白(ASC)，Caspase-1蛋白及mRNA水平。ELISA法检测巨噬细胞中IL-1β，IL-18含量。TUNEL染色检测心肌细胞及巨噬细胞凋亡水平。结果与假手术组相比，MI组大鼠心肌组织断裂、紊乱，炎性细胞浸润，间隙大量胶原纤维沉积，细胞凋亡增加，心肌组织中Caspase-8，GSDME蛋白及mRNA表达增加，差异具有统计学意义（t=16.19，27.60；21.18，23.73，均P<0.05）。与MI组相比，Z-IETD-FMK组大鼠心肌结构损伤改善，炎性细胞及胶原沉积减少，细胞凋亡减少，心肌组织中Caspase-8，GSDME蛋白及mRNA表达减少，差异具有统计学意义（t=20.34，14.56；11.97，24.46，均P<0.05）。与对照组相比，缺氧组巨噬细胞凋亡增加，巨噬细胞中Caspase-8，GSDME，NLRP3，ASC，Caspase-1蛋白及mRNA表达增加（t蛋白=17.53~120.90，tmRNA=18.42~60.30），巨噬细胞中IL-1β，IL-18含量增加（t=25.88，45.74），差异具有统计学意义（均P<0.05）；与缺氧组相比，Z-IETD-FMK组巨噬细胞凋亡减少，巨噬细胞中Caspase-8，GSDME，NLRP3，ASC，Caspase-1蛋白及mRNA表达减少（t蛋白=17.08~35.08，tmRNA=11.21~47.96），IL-1β，IL-18含量减少（t=27.38，25.82），差异具有统计学意义（均P<0.05）。结论下调Caspase-8/GSDME通路可改善MI大鼠心肌损伤及缺氧巨噬细胞焦亡水平。
Abstract:
Objective To explore the role of cysteine aspartic protease-8 (Caspase-8)/gasdermin E (GSDME) pathway in the regulation of macrophage pyroptosis in myocardial infarction (MI) rat model and its possible mechanism. Methods Thirty rats were randomly divided into sham operation group, MI group and Caspase-8 inhibition (Z-IETD-FMK) group, with 10 rats in each group. The cultured rat macrophages RMa-bm were divided into control group, hypoxia group and Z-IETD-FMK group. The pathological changes of myocardial tissue were detected by H&E staining. Masson staining was used to detect myocardial fibrosis. The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8, GSDME, NLR family Pyrin domain protein 3 (NLRP3), apoptosis-related speck-like protein (ASC) and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA. TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages. Results Compared with the sham operation group, myocardial tissue of rats in MI group was broken and disturbed, inflammatory cell infiltration, a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8, GSDME protein and mRNA in myocardial tissue increased, the differences were statistically significant (t=16.19, 27.60; 21.18, 23.73, all P<0.05). Compared with MI group, Z-IETD-FMK group improved myocardial structural damage, reduced inflammatory cells and collagen deposition, cell apoptosis decreased and decreased Caspase-8，GSDME protein and mRNA expressions in myocardial tissue, with statistical significance (t=20.34, 14.56; 11.97, 24.46, all P<0.05). Compared with the control group, the apoptosis of macrophages in hypoxia group was increased, and the protein and mRNA expressions of Caspase-8, GSDME, NLRP3, ASC, Caspase-1 in macrophages were increased (tprotein=17.53~120.90, tmRNA=18.42~60.30), the contents of IL-1β and IL-18 in macrophages were increased (t=25.88, 45.74), and the differences were staistically significant (all P<0.05). Compared with the hypoxia group, the apoptosis of macrophages in Z-IETD-FMK group was decreased, and the protein and mRNA expressions of Caspase-8, GSDME, NLRP3, ASC, Caspase-1 in macrophages were decreased (tprotein=17.08~35.08, tmRNA=11.21~47.96), IL-1β and IL-18 content decreased (t=27.38, 25.82), and the differences were staistically significant (all P<0.05), respectively. Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.

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备注/Memo

备注/Memo:
基金项目：河北省医学科学研究课题计划(20241914)。
作者简介：安丽伟（1988-），女，本科，主治医师，研究方向：心内科，E-mail：zhananlu25059976@163.com。
更新日期/Last Update: 2025-11-15