Yan Ruyu, Li Ying, Zhang Ling, Xia Ning, Liu Qi, Sun Hang, Guo Hui
Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China,
Int Urol Nephrol. 2015 May;47(5):861-8. doi: 10.1007/s11255-015-0954-8. Epub 2015 Mar 20.
PURPOSE: The effects of augmenter of liver regeneration (ALR) on the acute kidney injury (AKI) rats were investigated by measuring the inflammatory response associated with transcription factor nuclear factory (NF-κB) pathway. METHODS: The model of AKI rats was established by occluded the renal pedicles for 60 min and then released. After that, animals were treated with ALR (100 or 200 μg/kg). All rats were killed at different time points (24, 48, 72 h). Renal function and kidney histological changes were measured. The apoptosis of tubular cells was evaluated by TdT-mediated dUTP nick end labeling assay. Cytokines and chemokines were assessed by immunohistochemistry, enzyme-linked immunosorbent assay and real-time polymerase chain reaction (RT-PCR). The NF-κB p65 protein was analyzed by immunohistochemistry and RT-PCR, respectively. RESULTS: Ischemia reperfusion induced tubular cells necrosis and apoptosis, and ALR can significantly reduce this damages. The productions of MCP-1, IL-1β and IL-6 were lower in the group of ALR treatment, especially in the high-dose group. The inflammatory infiltrates were lower in the rats with administration of ALR. ALR mediated the level of cytokines and chemokines through inhibited the activation of NF-κB. CONCLUSION: ALR can improve renal function and inhibit the expression of inflammatory factors. This protects against renal ischemia reperfusion injury, which may be associated with preventing NF-κB activation in rats.
目的:通过检测与转录因子核因子κB(NF-κB)通路相关的炎症反应,研究肝再生增强因子(ALR)对急性肾损伤(AKI)大鼠的影响。 方法:通过夹闭肾蒂60分钟然后松开建立AKI大鼠模型。之后,动物接受ALR(100或200μg/kg)治疗。所有大鼠在不同时间点(24、48、72小时)处死。检测肾功能和肾脏组织学变化。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法评估肾小管细胞凋亡。通过免疫组织化学、酶联免疫吸附测定和实时聚合酶链反应(RT-PCR)评估细胞因子和趋化因子。分别通过免疫组织化学和RT-PCR分析NF-κB p65蛋白。 结果:缺血再灌注诱导肾小管细胞坏死和凋亡,而ALR可显著减轻这种损伤。ALR治疗组中单核细胞趋化蛋白-1(MCP-1)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的产生较低,尤其是高剂量组。给予ALR的大鼠炎症浸润较少。ALR通过抑制NF-κB的激活介导细胞因子和趋化因子水平。 结论:ALR可改善肾功能并抑制炎症因子的表达。这可防止肾缺血再灌注损伤,这可能与阻止大鼠NF-κB激活有关。
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