清除衰老细胞在减轻脓毒症小鼠急性肺损伤中的作用机制探讨  

Mechanistic analyses on the role of senescent cell clearance in alleviating acute lung injury in septic mice

作  者:贾艳慧 原毅轩 官浩 胡大海 Jia Yanhui;Yuan Yixuan;Guan Hao;Hu Dahai(Department of Burns and Cutaneous Surgery,Burn Center of PLA,the First Affiliated Hospital of Air Force Medical University,Xi′an 710032,China)

机构地区:[1]空军军医大学第一附属医院全军烧伤中心烧伤与皮肤外科,西安710032

出  处:《中华损伤与修复杂志(电子版)》2025年第1期55-60,共6页Chinese Journal of Injury Repair and Wound Healing(Electronic Edition)

基  金:国家自然科学基金青年项目(81901938)。

摘  要:目的探究细胞衰老对脓毒症小鼠急性肺损伤的影响。方法取45只8周龄雄性C57BL/6小鼠,随机分为假手术组、模型组及衰老细胞清除药物ABT-263处理组(ABT-263组),每组15只。采用盲肠结扎穿刺法构建脓毒症急性肺损伤小鼠模型,假手术组只暴露盲肠,不进行结扎和穿刺操作,ABT-263组造模后以100 mg/kg剂量ABT-263灌胃给药,1次/d。检测小鼠肺组织中细胞衰老标志物(p16INK4A和p21CIP1)、衰老相关分泌表型(SASP)相关成分炎症因子、趋化因子、基质金属蛋白酶、细胞增殖标志物Ki67及细胞周期相关分子的基因表达,并进行HE染色和β-半乳糖苷酶染色观察肺组织病理变化及检测肺泡巨噬细胞衰老情况。结果与假手术组相比,模型组肺组织中p16INK4A和p21CIP1表达及SASP相关基因表达显著升高,而Ki67表达显著降低。模型组肺泡巨噬细胞β-半乳糖苷酶阳性比例显著高于假手术组。与模型组相比,ABT-263组小鼠肺组织中p16INK4A和p21CIP1表达及SASP相关基因表达显著降低,而Ki67表达显著增加。ABT-263组肺泡巨噬细胞β-半乳糖苷酶阳性比例显著低于模型组。ABT-263组肺组织损伤评分显著低于模型组。结论细胞衰老与脓毒症急性肺损伤相关,清除衰老细胞可以显著缓解脓毒症急性肺损伤。Objective To explore the impact of cellular senescence on acute lung injury in septic mice.Methods Forty-five 8-week-old male C57BL/6 mice were selected and randomly divided into sham surgery group,model group,and ABT-263-treated group for senescent cells(ABT-263 group),with 15 mice in each group.The acute lung injury in sepis model was set up by cecal ligation and puncture.The sham surgery group only exposed the cecum without performing ligation or puncture procedures.The ABT-263 group was given intragastric administration of ABT-263 at a dose of 100 mg/kg once a day.The expression of cellular senescence markers(p16INK4A and p21CIP1),senescence-associated secretory phenotype(SASP)related inflammatory cytokines,chemokines,matrix metalloproteinases,cell proliferation marker Ki67 and cell cycle-related molecules in the lung tissues of the mice were detected.Additionally,pathological changes in lung tissue and the senescence of alveolar macrophages were observed using HE staining and β-galactosidase staining.Results Compared to the sham surgery group,the expression of p16INK4A and p21CIP1 in the lung tissues,and the expression of SASP-related genes of the model group were significantly higher,while the expression of Ki67 was significantly lower.The proportion of alveolar macrophage β-galactosidasepositive cells in the model group was significantly higher than that in the sham surgery group.Compared to the model group,the expression of p16INK4A and p21CIP1 in the lung tissues,and the expression of SASPrelated genes in the ABT-263 group were significantly lower,while the expression of Ki67 was significantly increased.The proportion of alveolar macrophage β-galactosidase-positive cells in the ABT-263 group was significantly lower than that in the model group.The injury score of lung tissues in the ABT-263 group was significantly lower than that in the model group.Conclusion Cellular senescence is correlated with acute lung injury in sepsis,and the elimination of senescent cells can significantly alleviate acute lung

关 键 词:脓毒症 急性肺损伤 细胞衰老 ABT-263 

分 类 号:R73[医药卫生—肿瘤]

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象