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ATP6V1A缺失导致脓毒症心脏驻留巨噬细胞清除能力损伤
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作者 杨顺心 周远群 +3 位作者 向鑫明 刘良明 李涛 胡弋 《陆军军医大学学报》 CAS 2024年第23期2599-2607,共9页
目的 探讨脓毒症后心脏驻留巨噬细胞的清除能力及其机制。方法 利用盲肠穿孔结扎术建立脓毒症小鼠模型,将30只雄性C57BL/6小鼠(8周龄,体质量20~25 g)按随机数字抽样法分为假手术组(Sham组,n=15)和脓毒症模型组(Sepsis组,n=15)。使用免... 目的 探讨脓毒症后心脏驻留巨噬细胞的清除能力及其机制。方法 利用盲肠穿孔结扎术建立脓毒症小鼠模型,将30只雄性C57BL/6小鼠(8周龄,体质量20~25 g)按随机数字抽样法分为假手术组(Sham组,n=15)和脓毒症模型组(Sepsis组,n=15)。使用免疫荧光技术标记心肌细胞与巨噬细胞观察小鼠心肌细胞凋亡及心脏驻留巨噬细胞对心肌细胞的吞噬情况。提取心脏驻留巨噬细胞进行转录组学测序,观察脓毒症后心脏驻留巨噬细胞的功能变化。在细胞水平建立心脏驻留巨噬细胞系,即正常组(RAC组);用LPS处理RAC组细胞后,即脓毒症组(RAC+LPS组)。观察2组间对凋亡心肌细胞清除能力的差异;使用DQ-BSA-RED溶酶体活性检测探针、Lyso-Sensor yellow/bule染料、ELISA以及蛋白质印迹实验法检测心脏驻留巨噬细胞溶酶体功能、溶酶体重要水解酶活性及蛋白表达、囊泡型腺苷三磷酸酶(vacuolar-type adenosine triphosphatases,V-ATPase)含量及其相关亚基的改变。结果 与Sham组相比,Sepsis组小鼠心肌细胞凋亡数量增加(P<0.05),心脏巨噬细胞对心肌细胞的吞噬增加(P<0.05),转录组学结果分析发现脓毒症后心脏驻留巨噬细胞的溶酶体相关功能显著失调。体外实验结果显示,与RAC组相比,RAC+LPS组对凋亡心肌细胞的碎片化能力降低,溶酶体的黄色荧光强度明显减弱(P<0.05),溶酶体水解酶活性降低(P<0.05)。此外,LPS处理显著降低了心脏驻留巨噬细胞V-ATPase及其主要亚基ATP6V1A的活性和表达(P<0.05)。结论 脓毒症后心脏驻留巨噬细胞对凋亡心肌细胞的清除能力降低,其机制可能与其溶酶体V-ATPase重要亚基ATP6V1A和溶酶体水解酶活性降低有关。 展开更多
关键词 脓毒症心脏功能障碍 心脏驻留巨噬细胞 溶酶体 囊泡型腺苷三磷酸酶
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Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis 被引量:8
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作者 Fa-chao CHEN Yin-chuan XU Zhao-cai ZHANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2020年第7期537-548,共12页
Objective:The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic patients.Methods:Brain natriur... Objective:The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic patients.Methods:Brain natriuretic peptide(BNP),cardiac troponin I(cTnI),and heart-type fatty acid-binding protein(h-FABP)in 147 septic patients were assayed within 6 h after admission.We also determined the plasma levels of myeloperoxidase(MPO)and pregnancyassociated plasma protein-A(PAPP-A).The receiver operating characteristic(ROC)curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality.Also,the ROC curve,net reclassification improvement(NRI),and integrated discrimination improvement(IDI)indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality.Results:Our statistics revealed that only h-FABP independently predicted SIMD(P<0.05).The addition of MPO and cTnI to h-FABP for SIMD prediction provided an NRI of 18.7%(P=0.025)and IDI of 3.3%(P=0.033).However,the addition of MPO or cTnI to h-FABP did not significantly improve the predictive ability of h-FABP to SIMD,as evidenced by the area under the curve(AUC),NRI,and IDI(all P>0.05).A history of shock and MPO were independent predictors of mortality in septic patients(both P<0.05).The addition of PAPP-A and h-FABP to MPO resulted in a mortality prediction with NRI of 25.5%(P=0.013)and IDI of 2.9%(P=0.045).However,this study revealed that the addition of h-FABP or PAPP-A to MPO did not significantly improve the ability to predict mortality,as evidenced by the AUC,NRI,and IDI(all P>0.05).Conclusions:The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers. 展开更多
关键词 Multi-biomarker Myocardial dysfunction SEPSIS MORTALITY
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