Exogenous hydrogen sulfide protects against high glucose‑induced inflammation and cytotoxicity in H9c2 cardiac cells.
Exogenous hydrogen sulfide protects against high glucose‑induced inflammation and cytotoxicity in H9c2 cardiac cells.
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DOI：
10.3892/mmr.2016.5846
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发表时间：
2016-11
影响因子：
3.4
通讯作者：
Zena Huang;Xiaobian Dong;X. Zhuang;Xun Hu;Lichun Wang;X. Liao
中科院分区：
文献类型：
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作者：
Zena Huang;Xiaobian Dong;X. Zhuang;Xun Hu;Lichun Wang;X. Liao
高血压在糖尿病心肌病的发病机制中起重要作用。本研究的目的是探讨外源性硫化氢（H2S）是否通过抑制p38丝裂原活化蛋白激酶（MAPK）/核因子-κB（NF-κB）、环氧合酶-2（考克斯-2）和诱导型一氧化氮合酶（iNOS）信号通路来对抗高糖诱导的心肌细胞炎症和细胞毒性。将大鼠H9 c2心肌细胞暴露于33 mM葡萄糖（高糖，HG）24 h，以刺激HG诱导的细胞毒性。在HG暴露前，用NaHS（H2S供体）预处理一组细胞，并使用Cell Counting Kit-8测定法测定细胞活力。Western blotting检测p38 MAPK、NF-κB磷酸化p65亚基、iNOS、考克斯-2和caspase-3蛋白表达水平; ELISA检测IL-1β和IL-6蛋白表达水平。NaHS预处理H9 c2细胞30 min后，HG可明显抑制p38 MAPK和NF-κB的表达。此外，NaHS预处理显著减弱了p38 MAPK/NF-κB介导的细胞毒性和炎症，表现为细胞活力显著增加，iNOS、考克斯-2、IL-1β和IL-6表达水平显著降低。此外，用NaHS处理细胞显著降低了caspase-3的表达，这表明NaHS减弱了HG诱导的细胞凋亡。总之，本研究的结果提供了证据表明，外源性H2S保护H9 c2心肌细胞免受HG诱导的细胞毒性和炎症。H2S可能通过抑制p38 MAPK/NF-κB、考克斯-2和iNOS信号通路发挥这些细胞保护作用。
Hyperglycemia serves an important role in the pathogenesis of diabetic cardiomyopathy. The aim of the present study was to investigate whether exogenous hydrogen sulfide (H2S) protects against high glucose‑induced inflammation and cytotoxicity in cardiac cells by inhibiting the p38 mitogen‑activated protein kinase (MAPK)/nuclear factor‑κB (NF‑κB), cyclooxygenase‑2 (COX‑2) and inducible nitric oxide synthase (iNOS) signaling pathways. Rat H9c2 myocardium cells were exposed to 33 mM glucose (high glucose, HG) for 24 h to stimulate HG‑induced cytotoxicity. One group of cells was pretreated with NaHS (a donor of H2S) prior to HG exposure, and cell viability was determined using the Cell Counting Kit‑8 assay. The protein expression levels of p38MAPK, the phosphorylated p65 subunit of NF‑κB, iNOS, COX‑2 and caspase‑3 were analyzed by western blotting, and the protein expression levels of interleukin (IL)‑1β and IL‑6 were detected by enzyme‑linked immunosorbent assay (ELISA). Pretreatment of H9c2 cells with NaHS for 30 min prior to exposure to HG significantly ameliorated the expression of p38MAPK and NF‑κB. In addition, pretreatment with NaHS markedly attenuated p38MAPK/NF‑κB‑mediated cytotoxicity and inflammation, as evidenced by the significant increase in cell viability and decrease in iNOS, COX‑2, IL‑1β and IL‑6 expression levels. Furthermore, treatment of cells with NaHS significantly decreased the expression of caspase‑3, which suggested that NaHS attenuated HG‑induced apoptosis. In conclusion, the results of the present study provided evidence to suggest that exogenous H2S protects against HG‑induced cytotoxicity and inflammation in H9c2 cardiac cells. H2S may exert these cytoprotective effects via inhibition of the p38MAPK/NF‑κB, COX‑2 and iNOS signaling pathways.