Dexmedetomidine Ameliorates Acute Stress-Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway.
Dexmedetomidine Ameliorates Acute Stress-Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway.
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右美托咪定通过抑制 ROS/JNK 信号通路减轻氧化应激和细胞凋亡，从而改善急性应激性肾损伤
DOI：
10.1155/2018/4035310
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发表时间：
2018
影响因子：
--
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Chen Y;Feng X;Hu X;Sha J;Li B;Zhang H;Fan H
急性应激通过过度氧化应激诱导组织损伤。据报道，右美托咪定（DEX）具有抗氧化作用。然而，DEX对急性应激所致肾损伤的保护作用及其相关的分子机制尚不清楚。在本文中，大鼠被迫游泳15分钟，然后在有/没有DEX（30 μg/kg）的情况下束缚应激3小时。通过田间试验验证了模型的建立。进行肾功能（肌酸酐、尿素氮）、组织病理学、氧化应激（丙二醛、谷胱甘肽和超氧化物歧化酶）和细胞凋亡（转移酶介导的dUTP缺口末端标记）评估。凋亡的定位通过切割的caspase 3蛋白的免疫组织化学测定。此外，采用Western blot方法检测死亡受体介导的信号通路、线粒体信号通路、内质网应激（ERS）信号通路和ROS/JNK信号通路中的关键蛋白。我们发现，DEX显着改善肾功能不全，改善肾损伤，减少氧化应激，减轻细胞凋亡。DEX还抑制去甲肾上腺素（NE）的释放，减少活性氧（ROS）的产生，并抑制JNK磷酸化。此外，DEX下调Bax的表达，细胞色素C，裂解半胱天冬酶9，裂解半胱天冬酶3蛋白在Doppler依赖性途径。总之，DEX通过抑制ROS/JNK通路减少氧化应激和细胞凋亡，保护大鼠免受急性应激诱导的肾损伤。
Acute stress induces tissue damage through excessive oxidative stress. Dexmedetomidine (DEX) reportedly has an antioxidant effect. However, protective roles and related potential molecular mechanisms of DEX against kidney injury induced by acute stress are unknown. Herein, rats were forced to swim 15 min followed by restraint stress for 3 h with/without DEX (30 μg/kg). Successful model establishment was validated by an open-field test. Assessment of renal function (creatinine, urea nitrogen), histopathology, oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), and apoptosis (transferase-mediated dUTP nick end labeling) was performed. Localization of apoptosis was determined by immunohistochemistry of cleaved caspase 3 protein. In addition, key proteins of the death receptor-mediated pathway, mitochondrial pathway, endoplasmic reticulum stress (ERS) pathway, and ROS/JNK signaling pathway were measured by Western blot. We found that DEX significantly improved renal dysfunction, ameliorated kidney injury, reduced oxidative stress, and alleviated apoptosis. DEX also inhibited the release of norepinephrine (NE), decreased the production of reactive oxygen species (ROS), and inhibited JNK phosphorylation. Additionally, DEX downregulated the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3 proteins in mitochondria-dependent pathways. In summary, DEX protects against acute stress-induced kidney injury in rats by reducing oxidative stress and apoptosis via inhibition of the ROS/JNK pathway.
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