摘要
目的探讨半胱氨酸蛋白酶-1(Caspase-1)对小鼠急性心肌梗死期血管通透性的影响及其分子机制。方法本研究选取C57野生型(WT)小鼠和Caspase-1基因缺陷小鼠(Casp1-/-)为研究对象, 建立急性心肌梗死(AMI)模型;通过构建糖氧剥夺(OGD)模型来模拟内皮细胞中的AMI环境。2, 3, 5-氯化三苯基四氮唑(TTC)染色法观察各组小鼠心梗面积的大小;免疫印迹法检测相关蛋白表达水平的变化;免疫荧光染色法检测血管渗透性及观察各组黏附连接标志物的分布;酶联免疫吸附试验(ELISA)检测法检测细胞因子浓度, 组间比较采用t检验。结果 Casp1-/--AMI组梗死区域面积低于WT-AMI组(33.83±7.01比56.78±11.60, t=2.93, P<0.05);Casp1-/--AMI组VE-cadherin的表达量高于WT-AMI组(0.87±0.14比0.43±0.11, t=4.37, P<0.05);OGD条件下VE-cadherin的表达具有相同的变化;Casp1-/--AMI组细胞因子浓度低于WT-AMI组[(57.41±5.34)、(52.40±6.00) pg/ml比(73.80±6.16)、(69.84±4.68) pg/ml, t=4.50、t=5.13, P<0.01];Casp1-/-+Echinulin组VE-cadherin的表达水平明显低于Casp1-/--normal组(0.31±0.05比0.95±0.15, t=7.23, P<0.01), 差异均有统计学意义。结论 Caspase-1基因缺陷可以通过调控核因子-κB通路发挥维持血管通透性, 保护心脏功能的积极作用。
Objective To investigate the effect of cysteine proteinase-1(Caspase-1)on vascular permeability during acute myocardial infarction(AMI)in mice and its molecular mechanism.Methods In this study,C57 wild-type(WT)mice and Caspase-1 gene deficient mice(Casp1-/-)were selected to establish an AMI model.The AMI environment in endothelial cells was simulated by constructing a glyoxylate deprivation(OGD)model.2,3,5-triphenyltetrazolium chloride(TTC)staining was used to observe the size of the infarct area in each group of mice.The changes in the expression level of related proteins were detected by immunoblotting.The vascular permeability and the distribution of adhesion-linked markers in each group were detected by immunofluorescence staining.The cytokine concentration was detected by enzyme linked immunosorbent assay(ELISA).Thet-test was used for comparison between groups.Results The infarct area in the Casp1-/--AMI group was lower than that in the WT-AMI group(33.83±7.01 vs.56.78±11.60,t=2.93,P<0.05).The expression of VE-cadherin in the Casp1-/--AMI group was higher than that in the WT-AMI group(0.87±0.14 vs.0.43±0.11,t=4.37,P<0.05).VE-cadherin expression under OGD conditions had the same changes.Cytokine concentrations were lower in the Casp1-/--AMI group than in the WT-AMI group[(57.41±5.34),(52.40±6.00)pg/ml vs.(73.80±6.16),(69.84±4.68)pg/ml,t=4.50,5.13,P<0.01].The expression level of VE-cadherin was significantly lower in the Casp1-/-+Echinulin group than in the Casp1-/-normal group(0.31±0.05 vs.0.95±0.15,t=7.23,P<0.01).Conclusion Caspase-1 gene defect can play a positive role in maintaining vascular permeability and protecting cardiac function by regulating the nuclear factor-κB pathway.
作者
梁敬天
贾才力
晁志祥
张力
秦西淳
刘修成
张昊
Liang Jingtian;Jia Caili;Chao Zhixiang;Zhang Li;Qin Xichun;Liu Xiucheng;Zhang Hao(Laboratory of Thoracic Surgery,Xuzhou Medical University,Xuzhou 221002,China;Department of Thoracic Surgery,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221002,China)
出处
《中华实验外科杂志》
CAS
北大核心
2023年第8期1522-1525,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金(81870235)
江苏省社会发展重点研发计划(BE2019643)。
关键词
半胱氨酸蛋白酶-1
急性心肌梗死
黏附连接
核因子-ΚB
Cysteinyl aspartate specific proteinase-1
Acute myocardial infarction
Tight junctions
Nuclear factor-κB
