Triptolide reduces ischemia/reperfusion injury in rats and H9C2 cells via inhibition of NF‑κB, ROS and the ERK1/2 pathway.
Triptolide reduces ischemia/reperfusion injury in rats and H9C2 cells via inhibition of NF‑κB, ROS and the ERK1/2 pathway.
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雷公藤甲素通过抑制 NF-κB、ROS 和 ERK1/2 通路来减少大鼠和 H9C2 细胞的缺血/再灌注损伤
DOI：
10.3892/ijmm.2018.3537
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发表时间：
2018-06
影响因子：
5.4
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Yang B;Yan P;Yang GZ;Cao HL;Wang F;Li B
心肌缺血/再灌注（I/R）可引起心肌细胞损伤，但其机制尚不清楚。以前的研究表明，雷公藤内酯醇（TP）对脑细胞I/R具有保护作用。本研究旨在观察茶多酚对心肌细胞的保护作用，并探讨其在心肌缺血再灌注损伤中的作用机制。用TP预处理大鼠和心肌H9 C2细胞I/R，并在体内和体外评估细胞损伤。采用苏木精-伊红染色和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测大鼠心肌组织I/R损伤。ELISA法检测肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-1 β）、白细胞介素6（IL-6）等炎症因子。生化分析进行了评价超氧化物歧化酶，丙二醛和过氧化氢酶的生物活性。此外，使用细胞计数试剂盒8测定法测量H9 C2细胞的活力。流式细胞仪检测细胞凋亡和活性氧（ROS）的产生。此外，使用蛋白质印迹分析测量与凋亡、过氧化物和炎症相关的蛋白质的表达水平。H9 C2细胞也用N-乙酰半胱氨酸和吡咯烷二硫代氨基甲酸酯处理，并在过氧化或I/R后评估细胞损伤。结果表明，茶多酚在体内外对心肌细胞有明显的保护作用。TP降低炎症反应，通过核因子-κB抑制测定。此外，TP降低ROS介导的脂质过氧化，减少ROS的产生。TP还通过激活细胞外信号调节激酶1/2途径抑制细胞凋亡。结论：茶多酚对心肌细胞I/R损伤具有保护作用，其机制可能包括抗炎、抗氧化和抗凋亡作用。
Myocardial ischemia/reperfusion (I/R) induces cardiac cell injury; however, the mechanism underlying cardiac damage remains unclear. A previous study demonstrated that triptolide (TP) exerts protective effects against I/R in cerebral cells. The present study aimed to evaluate the protective effects of TP on cardiac cells, and investigated the potential mechanisms involved in I/R-induced damage. Rats and cardiac H9C2 cells undergoing I/R were pretreated with TP, and cell damage was assessed in vivo and in vitro. Hematoxylin and eosin and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining were employed to evaluate I/R injury in rat cardiac tissue. Inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, were detected by ELISA. Biochemical analyses were performed to evaluate the bioactivity of superoxide dismutase, malondialdehyde and catalase. In addition, viability of H9C2 cells was measured using the Cell Counting kit 8 assay. Flow cytometry was used to evaluate cell apoptosis and reactive oxygen species (ROS) generation. Furthermore, the expression levels of proteins associated with apoptosis, peroxide and inflammation were measured using western blot analysis. H9C2 cells were also treated with N-acetylcysteine and pyrrolidine dithiocarbamate, and cell injury was assessed after peroxidation or I/R. The results demonstrated that TP exerted a significant protective effect on cardiac cells in vivo and in vitro. TP reduced the inflammatory response, as determined by nuclear factor-κB inhibition. In addition, TP decreased ROS-mediated lipid peroxidation, and reduced ROS generation. TP also inhibited cell apoptosis by activating the extracellular signal-regulated kinase 1/2 pathway. In conclusion, TP may protect cardiac cells from I/R injury; the potential protective mechanisms of TP against I/R include anti-inflammatory action, antioxidation and apoptotic resistance.
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DOI：
10.1073/pnas.94.8.3668
发表时间：
1997-04-15
影响因子：
11.1
作者：
Hsu, YT;Wolter, KG;Youle, RJ
通讯作者：
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DOI：
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发表时间：
2016-07-01
影响因子：
5.4
作者：
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