Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway.
Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway.
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萝卜硫素通过调节 Nrf2 介导的氧化应激和 NLRP3 炎症途径来保护胰腺腺泡细胞损伤。
DOI：
10.1155/2016/7864150
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发表时间：
2016
影响因子：
--
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Dong Z;Shang H;Chen YQ;Pan LL;Bhatia M;Sun J
急性胰腺炎(AP)的特征是腺泡内蛋白水解酶的早期激活，随后是腺泡细胞死亡和炎症。细胞氧化应激是这些病理事件背后的一个关键机制。萝卜硫素(SFN)是一种天然的有机硫抗氧化剂，对AP有未知的作用。在这里，我们研究了三七总皂苷对AP细胞氧化和炎症的调节作用。在BALB/c小鼠中，用蓝天蓝高刺激性诱发AP。治疗组术前单次给予5 mg/kg三七总皂苷，连续3d。我们发现，给予SFN可以减轻胰腺损伤，如血清淀粉酶、胰腺水肿和髓过氧化物酶，以及组织学检查。SFN可逆转AP引起的氧化应激标志物的失调，包括胰腺丙二醛和氧化还原酶、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)。在腺泡细胞中，SFN处理上调了核因子红系相关因子2(Nrf2)的表达，并上调了Nrf2调节的氧化还原基因，包括苯醌氧化还原酶-1、血红素氧化酶-1、SOD1和GPX1。此外，SFN选择性地抑制蓝蛋白诱导的富含亮氨酸重复序列家族(NLRP3)炎症体的激活，同时减少核因子(NF-)κB的激活，并调节NF-κB反应细胞因子的表达。综上所述，我们的数据表明，SFN调节腺泡细胞中NRF2介导的氧化应激和NLRP3/NF-κB炎症通路，从而保护AP。
Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κB activation and modulated NF-κB-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF-κB inflammatory pathways in acinar cells, thereby protecting against AP.
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影响因子：
4.6
作者：
Jin, Wei;Wang, Handong;Yan, Wei;Xu, Lizhi;Wang, Xiaoliang;Zhao, Xiaoning;Yang, Xiaohe;Chen, Gang;Ji, Yan
通讯作者：
Ji, Yan
影响因子：
4.8
作者：
Elbling, L;Weiss, RM;Mickshe, M
通讯作者：
Mickshe, M
影响因子：
12.4
作者：
Kallifatidis, Georgios;Labsch, Sabrina;Herr, Ingrid
通讯作者：
Herr, Ingrid
影响因子：
--
作者：
Bhatia, Madhav;Hegde, Akhil
通讯作者：
Hegde, Akhil
影响因子：
5.2
作者：
Li, Yanyan;Zhang, Tao;Li, Xiaoqin;Zou, Peng;Schwartz, Steven J.;Sun, Duxin
通讯作者：
Sun, Duxin