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首页> 外文期刊>Cellular Physiology and Biochemistry >The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway
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The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

机译：ATP敏感性K +通道的开放可通过抑制ROS-TLR4-坏死病的途径保护H9c2心肌细胞免受高糖诱导的损伤和炎症的侵害。

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>Background/Aims: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. Methods: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. Results: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. Conclusion: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.
机译：> 背景/目标： 高血糖会激活多种信号分子，包括活性氧（ROS），toll​​样受体4（TLR4），受体相互作用蛋白3（ RIP3，一种促进坏死的激酶），介导高血糖引起的心脏损伤。本研究探讨了ROS-TLR4-坏死病途径的抑制是否有助于保护ATP敏感的K + （K ATP ）通道开放，防止高糖诱导的心脏损伤和炎。 方法： 用35 mM葡萄糖（HG）处理H9c2心脏细胞，以建立HG诱导的损伤模型。用western blot检测RIP3和TLR4的表达。测定ROS的产生，细胞活力，线粒体膜电位（MMP）和炎性细胞因子的分泌作为损伤指标。 结果： HG增加了TLR4和RIP3的表达。 Necrostatin-1（Nec-1，一种坏死病抑制剂）或TAK-242（TLR4的抑制剂）共同治疗可减轻HG诱导的RIP3的上调。重氮（DZ，线粒体K ATP 通道开放剂）或吡那地尔（Pin，非选择性K ATP 通道开放剂）或N-乙酰基-L-半胱氨酸（NAC， ROS清道夫）预处理阻止了TLR4和RIP3的上调。此外，用DZ或Pin或NAC进行预处理，或与TAK-242或Nec-1共同处理可减轻HG诱导的细胞活力降低，并增加ROS生成，MMP丢失和炎性细胞因子分泌。但是，可以进行5-羟基癸酸（5-HD，一种线粒体K ATP 通道阻滞剂）或格列本脲（Gli，一种非选择性K ATP 通道阻滞剂）预处理没有加重HG诱导的损伤和炎症。 结论： K ATP 通道的开放可通过抑制ROS-TLR4-坏死病途径来保护H9c2细胞免受HG诱导的损伤和炎症。

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