Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.
Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.
复制标题
右美托咪定抑制 TLR4/NF-κ B 激活并减少大鼠原位自体肝移植后的急性肾损伤
DOI：
10.1038/srep16849
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发表时间：
2015-11-20
影响因子：
4.6
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
Yao H;Chi X;Jin Y;Wang Y;Huang P;Wu S;Xia Z;Cai J
接受原位肝移植的患者经常会出现急性肾损伤（AKI）。 Toll样受体4（TLR4）/核因子-кB（NF-кB）通路在AKI中发挥作用。右美托咪定 (Dex) 已被证明可以减轻 AKI。本研究旨在确定肝移植诱发的AKI是否与炎症反应相关，并评估右美托咪定预处理对原位自体肝移植（OALT）大鼠肾脏的影响。 77 只成年雄性大鼠被随机分为 11 组。评估肾脏组织病理学以及血尿素氮（BUN）和血清肌酐（SCr）水平。测量肾组织中 TLR4、NF-κB、肿瘤坏死因子-α 和白介素-1β 的水平。 OALT 导致显着的肾功能损害和组织损伤。右美托咪定预处理可降低 BUN 和 SCr 水平，并减少肾脏病理损伤、TLR4 表达、NF-κB 易位和细胞因子产生。右美托咪定的作用可通过阿替美唑和 BRL44408 预处理而逆转，但 ARC239 则不能逆转。使用α2A-肾上腺素受体siRNA证实了这些结果，该受体逆转了右美托咪定对减轻缺氧复氧诱导的NRK-52E细胞损伤的保护作用。总之，右美托咪定预处理可减轻 OALT 诱导的大鼠 AKI，这可能与其抑制 TLR4/MyD88/NF-κB 通路激活有关。肾脏保护作用与α2A-肾上腺素能受体亚型有关。
Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-кB(NF-кB) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-κB, tumor necrosis factor-α, and interleukin-1β levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-κB, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using α2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-κB pathway activation. The renoprotective effects are related to α2A-adrenergic receptor subtypes.