Effects of Lipid Peroxidation-Mediated Ferroptosis on Severe Acute Pancreatitis-Induced Intestinal Barrier Injury and Bacterial Translocation.
Effects of Lipid Peroxidation-Mediated Ferroptosis on Severe Acute Pancreatitis-Induced Intestinal Barrier Injury and Bacterial Translocation.
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DOI：
10.1155/2021/6644576
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发表时间：
2021
影响因子：
--
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Ma D;Jiang P;Jiang Y;Li H;Zhang D
铁凋亡是最近认识到的一种类型的调节性细胞死亡，其特征在于铁和脂质过氧化介导的非凋亡性细胞死亡。然而，铁凋亡是否参与重症急性胰腺炎（SAP）引起的肠屏障损伤尚不清楚。本研究的目的是研究铁凋亡是否参与SAP诱导的肠屏障损伤，特别是肠上皮细胞（IEC）的死亡，并确定是否铁凋亡的抑制将改善肠屏障损伤，防止细菌移位（BT）。采用胰胆管逆行灌注5%牛磺胆酸钠建立SAP大鼠模型。将大鼠分为假手术组（SO）、SAP诱导的肠屏障损伤组（SAP）和铁凋亡抑制剂LiP-1（SAP + Lip）组。测定大鼠血清指标。此外，还观察到与铁凋亡相关的生化和形态学变化，包括肠组织中的铁积累、脂质过氧化水平和线粒体收缩。苏木精染色和伊红染色用于评估组织学组织变化。采用Western blot、RT-PCR和免疫荧光染色等方法分析铁凋亡相关蛋白和基因的表达以及紧密连接的表达。16 S rDNA序列分析检测到BT。结果表明，SAP大鼠IEC铁凋亡明显，铁凋亡是由脂质过氧化反应介导的。IEC的特异性脂质过氧化明显上调铁凋亡，加重肠屏障损伤。此外，livestatin-1治疗降低血清损伤标志物的水平，减少脂质过氧化反应，减轻SAP大鼠肠道和急性远端器官损伤。此外，抑制铁凋亡减少BT。我们的研究结果是第一次证明，铁凋亡有助于SAP诱导的肠屏障损伤通过脂质过氧化介导的IEC死亡。这些结果表明，铁凋亡是SAP诱导的肠屏障损伤的潜在治疗靶点。
Ferroptosis is a recently recognized type of regulated cell death characterized by iron- and lipid peroxidation-mediated nonapoptotic cell death. However, whether ferroptosis is involved in severe acute pancreatitis- (SAP-) induced intestinal barrier injury is unknown. The aim of this study was to investigate whether ferroptosis is involved in SAP-induced intestinal barrier injury, particularly intestinal epithelial cell (IEC) death, and determine whether the inhibition of ferroptosis would ameliorate intestinal barrier injury and prevent bacterial translocation (BT). Sodium taurocholate (5%) was retrogradely perfused into the biliopancreatic duct to establish a rat model of SAP. The rats were divided into three groups: sham operation (SO), SAP-induced intestinal barrier injury (SAP), and ferroptosis inhibitor liproxstatin-1 (SAP + Lip). Serum indexes were measured in the rats. In addition, the biochemical and morphological changes associated with ferroptosis were observed, including iron accumulation in intestinal tissue, lipid peroxidation levels, and mitochondrial shrinkage. Hematoxylin staining and eosin staining were used to assess histological tissue changes. Western blot, RT-PCR, and immunofluorescent staining were performed to analyze the expression of ferroptosis-related proteins and genes as well as tight junction. BT was detected by 16S rDNA sequencing analysis. The results indicated that ferroptosis was significantly induced in the IECs from rats with SAP and ferroptosis was mediated by lipid peroxidation. The specific lipid peroxidation of IECs clearly upregulated ferroptosis and exacerbated intestinal barrier injury. Furthermore, treatment with liproxstatin-1 lowered the levels of serum damage markers, decreased lipid peroxidation, and alleviated intestinal and acute remote organ injury in SAP rats. In addition, inhibition of ferroptosis reduced BT. Our findings are the first to demonstrate that ferroptosis contributes to SAP-induced intestinal barrier injury via lipid peroxidation-mediated IEC death. These results suggest that ferroptosis is a potential therapeutic target for SAP-induced intestinal barrier injury.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
通讯作者：
Bayır H
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
p62-Keap1-NRF2 通路的激活可防止肝细胞癌细胞中的铁死亡。
DOI：
10.1002/hep.28251
发表时间：
2016-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sun X;Ou Z;Chen R;Niu X;Chen D;Kang R;Tang D
通讯作者：
Tang D
影响因子：
29.4
作者：
Petrov, Maxim S.;Shanbhag, Satyanarayan;Windsor, John A.
通讯作者：
Windsor, John A.