目的:探讨水飞蓟宾(S IL)在急性肝损伤中对肝细胞胀亡的影响及其机制。方法:用D氨基半乳糖(D G a lN)诱导大鼠急性肝损伤模型,用S IL进行干预,于不同时间点检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(A ST)活性及肝组织核转录因子κB(N...目的:探讨水飞蓟宾(S IL)在急性肝损伤中对肝细胞胀亡的影响及其机制。方法:用D氨基半乳糖(D G a lN)诱导大鼠急性肝损伤模型,用S IL进行干预,于不同时间点检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(A ST)活性及肝组织核转录因子κB(NFκB)活性,观察肝组织病理及肝细胞胀亡情况,并计算胀亡指数(O I)。结果:S IL能明显降低急性肝损伤模型大鼠血清ALT、A ST活性(P均<0.05),抑制NFκB活性(P<0.05),镜下显示肝组织损伤减轻程度,减少肝细胞胀亡,降低O I(P均<0.05)。结论:S IL可减少D G a lN所致大鼠肝细胞胀亡,其机制可能与抑制NFκB活性有关。展开更多
Oncosis is a special kind of non-apoptotic cell death mode. It is characterized by cellular swelling,organelle swelling,blebbingand increased membrane permeability. More and more attentions pay to the research of this...Oncosis is a special kind of non-apoptotic cell death mode. It is characterized by cellular swelling,organelle swelling,blebbingand increased membrane permeability. More and more attentions pay to the research of this field in recent years. The review discuss the recent advances of oncosis on pathological change,molecular mechanisms and detection approaches.展开更多
Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death characterized by reactive oxygen species(ROS) generation and lipid peroxidation.Here,we report a novel iron-dependent form of ferropt...Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death characterized by reactive oxygen species(ROS) generation and lipid peroxidation.Here,we report a novel iron-dependent form of ferroptosis induced by labile iron and investigate the mechanism underlying this process.We find that labile iron-induced ferroptosis is distinct from canonical ferroptosis and is linked to the mitochondrial pathway.Specifically,the mitochondrial calcium uniporter mediates the ferroptosis induced by labile iron.Interestingly,cells undergoing labile iron-induced ferroptosis exhibit cytoplasmic features of oncosis and nuclear features of apoptosis.Furthermore,labile iron-induced ferroptosis involves a unique set of genes.Finally,labile ironinduced ferroptosis was observed in liver subjected to acute iron overload in vivo.Our study reveals a novel form of ferroptosis that may be implicated in diseases caused by acute injury.展开更多
目的:通过建立大鼠急性胆道梗阻模型研究梗阻性黄疸时肝细胞死亡方式.方法:♂Wistar大鼠随机分为胆道结扎(BDL)组和对照(C)组.BDL组采用Yoshidome法建立急性胆道梗阻模型,7d后取材,应用流式细胞仪检测肝细胞胀亡和凋亡的百分比,HE染色...目的:通过建立大鼠急性胆道梗阻模型研究梗阻性黄疸时肝细胞死亡方式.方法:♂Wistar大鼠随机分为胆道结扎(BDL)组和对照(C)组.BDL组采用Yoshidome法建立急性胆道梗阻模型,7d后取材,应用流式细胞仪检测肝细胞胀亡和凋亡的百分比,HE染色和电镜观察肝组织病理组织学改变以及肝细胞凋亡、胀亡,并检测血清总胆红素TBIL,DBIL,ALP,γ-GT,ALT,AST和LDH水平.结果:BDL组胀亡和坏死细胞百分比均显著高于C组(胀亡:25.41%±2.18% vs 6.12%±1.69%;坏死:3.99%±1.24% vs 0.79%±0.29%;均P<0.05),而凋亡百分比显著低于C组(2.79%±1.43% vs 5.18%±1.87%,P<0.05).BDL组胀亡细胞百分比显著高于凋亡(25.41%±2.18% vs 2.79%±1.43%,P<0.05).肝病理组织学检查发现BDL组胆管增生,纤维结缔组织明显增生,肝细胞索排列紊乱,胀亡增加.BDL组血清TBIL,DBIL,ALP,γ-GT,AST,ALT和LDH水平均显著高于C组(P<0.05).结论:急性胆道梗阻时大鼠肝细胞死亡以胀亡为主,其肝功能损伤程度与肝细胞胀亡、凋亡有密切关系.展开更多
文摘目的:探讨水飞蓟宾(S IL)在急性肝损伤中对肝细胞胀亡的影响及其机制。方法:用D氨基半乳糖(D G a lN)诱导大鼠急性肝损伤模型,用S IL进行干预,于不同时间点检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(A ST)活性及肝组织核转录因子κB(NFκB)活性,观察肝组织病理及肝细胞胀亡情况,并计算胀亡指数(O I)。结果:S IL能明显降低急性肝损伤模型大鼠血清ALT、A ST活性(P均<0.05),抑制NFκB活性(P<0.05),镜下显示肝组织损伤减轻程度,减少肝细胞胀亡,降低O I(P均<0.05)。结论:S IL可减少D G a lN所致大鼠肝细胞胀亡,其机制可能与抑制NFκB活性有关。
文摘Oncosis is a special kind of non-apoptotic cell death mode. It is characterized by cellular swelling,organelle swelling,blebbingand increased membrane permeability. More and more attentions pay to the research of this field in recent years. The review discuss the recent advances of oncosis on pathological change,molecular mechanisms and detection approaches.
基金supported by the Beijing Natural Science Foundation (7202034)the National Natural Science Foundation of China (82170614)。
文摘Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death characterized by reactive oxygen species(ROS) generation and lipid peroxidation.Here,we report a novel iron-dependent form of ferroptosis induced by labile iron and investigate the mechanism underlying this process.We find that labile iron-induced ferroptosis is distinct from canonical ferroptosis and is linked to the mitochondrial pathway.Specifically,the mitochondrial calcium uniporter mediates the ferroptosis induced by labile iron.Interestingly,cells undergoing labile iron-induced ferroptosis exhibit cytoplasmic features of oncosis and nuclear features of apoptosis.Furthermore,labile iron-induced ferroptosis involves a unique set of genes.Finally,labile ironinduced ferroptosis was observed in liver subjected to acute iron overload in vivo.Our study reveals a novel form of ferroptosis that may be implicated in diseases caused by acute injury.
文摘目的:通过建立大鼠急性胆道梗阻模型研究梗阻性黄疸时肝细胞死亡方式.方法:♂Wistar大鼠随机分为胆道结扎(BDL)组和对照(C)组.BDL组采用Yoshidome法建立急性胆道梗阻模型,7d后取材,应用流式细胞仪检测肝细胞胀亡和凋亡的百分比,HE染色和电镜观察肝组织病理组织学改变以及肝细胞凋亡、胀亡,并检测血清总胆红素TBIL,DBIL,ALP,γ-GT,ALT,AST和LDH水平.结果:BDL组胀亡和坏死细胞百分比均显著高于C组(胀亡:25.41%±2.18% vs 6.12%±1.69%;坏死:3.99%±1.24% vs 0.79%±0.29%;均P<0.05),而凋亡百分比显著低于C组(2.79%±1.43% vs 5.18%±1.87%,P<0.05).BDL组胀亡细胞百分比显著高于凋亡(25.41%±2.18% vs 2.79%±1.43%,P<0.05).肝病理组织学检查发现BDL组胆管增生,纤维结缔组织明显增生,肝细胞索排列紊乱,胀亡增加.BDL组血清TBIL,DBIL,ALP,γ-GT,AST,ALT和LDH水平均显著高于C组(P<0.05).结论:急性胆道梗阻时大鼠肝细胞死亡以胀亡为主,其肝功能损伤程度与肝细胞胀亡、凋亡有密切关系.
