Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China.
J Cell Physiol. 2019 Aug;234(8):14068-14078. doi: 10.1002/jcp.28096. Epub 2019 Jan 7.
Acute stress is a frequent and unpredictable disease for many animals. Stress is widely considered to affect liver function. However, the underlying mechanism by which dexmedetomidine (DEX) attenuates acute stress-induced liver injury in rats remains unclear. In this study, we used forced swimming for 15 min and acute 3-hr restraint stress model. Behavioral tests and changes in norepinephrine levels confirmed the successful establishment of the acute stress model. Acute stress-induced liver injury, evidenced by hematoxylin and eosin-stained pathological sections and increased serum aminotransferase and aspartate aminotransferase levels, was reduced in DEX-treated livers. Reactive oxygen species and oxidative stress levels were dramatically decreased with DEX treatment compared with acute stress-induced liver injury. DEX significantly reduced acute stress-induced liver inflammation and apoptosis, as assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and inflammation and apoptosis-related protein levels. DEX treatment also effectively inhibited acute stress-induced c-Jun N-terminal kinase (JNK), P38, and BAD signaling pathway activation, and significantly induced MKP-1 activation. Thus, DEX has a protective effect on acute-stress-induced liver injury by reducing inflammation and apoptosis, which suggests a potential clinical application for DEX in stress syndrome.
急性应激是许多动物常见且不可预测的疾病。应激被广泛认为会影响肝功能。然而，右美托咪定（DEX）减轻大鼠急性应激性肝损伤的潜在机制尚不清楚。在本研究中，我们使用 15 分钟强制游泳和 3 小时急性束缚应激模型。行为测试和去甲肾上腺素水平的变化证实了急性应激模型的成功建立。DEX 处理的肝脏中，苏木精和伊红染色的病理切片以及血清转氨酶和天冬氨酸转氨酶水平的升高表明急性应激诱导的肝损伤减少。与急性应激诱导的肝损伤相比，DEX 处理可显著降低活性氧和氧化应激水平。DEX 通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色和炎症及凋亡相关蛋白水平评估，可显著减轻急性应激诱导的肝炎症和凋亡。DEX 治疗还可有效抑制急性应激诱导的 c-Jun N 末端激酶（JNK）、P38 和 BAD 信号通路的激活，并显著诱导 MKP-1 的激活。因此，DEX 通过减少炎症和凋亡对急性应激诱导的肝损伤具有保护作用，这表明 DEX 在应激综合征中的潜在临床应用。
