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N-乙酰半胱氨酸对细菌内毒素诱发急性肾损伤的保护作用及机制

Protective effect and mechanism of N-acetylcysteine on acute kidney injury induced by bacterial endotoxins
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摘要 目的 研究N-乙酰半胱氨酸(NAC)对细菌内毒素(LPS)诱发急性肾损伤(AKI)的保护作用及其机制。方法 雄性小鼠被随机分为4组:LPS处理组小鼠经腹腔(i.p.)给予2 mg/kg的LPS;NAC+LPS组于LPS(2 mg/kg, i.p.)处理时和处理后9 h经灌胃各给予100 mg/kg的NAC;对照组和NAC组给予等量的生理盐水或NAC。LPS处理后2 h每组剖杀6只小鼠,余下小鼠于LPS处理后18 h剖杀,取血清和肾脏。结果 LPS处理后血BUN和肌酐水平显著升高,肾脏出现明显的病理损害。NAC处理可显著减轻LPS引起的肾功能损伤和病理损害。LPS处理后肾脏组织促炎细胞因子TNF-α、IL-6、IL-1β和趋化因子Mip2、Kc、Mcp1 mRNA水平显著升高,NAC处理组显著对抗LPS上调肾脏组织促炎细胞因子和趋化因子的基因表达。LPS处理后血清TNF-α和KC蛋白水平显著升高;NAC处理显著对抗LPS升高血清TNF-α和KC蛋白水平。LPS处理后,肾脏核蛋白NF-κB p65水平显著升高,而NAC处理显著抑制LPS激活肾脏NF-κB p65信号。结论 NAC减轻LPS诱发的AKI,其机制可能是通过抑制NF-κB信号介导的肾脏炎症反应。 Objective To investigate the protective effect of N-acetylcysteine(NAC)on lipopolysaccharide(LPS)-induced acute kidney injury(AKI)and its mechanism.Methods Male mice were randomly divided into four groups:In LPS group,mice were intraperitoneally injected with single dose of LPS(2 mg/kg).In NAC+LPS group,mice were treated with two doses of NAC(100+100 mg/kg,i.g),one injected immediately after LPS and the other injected 9 h after LPS.The control group and the NAC group were given equal amounts of normal saline or NAC.6 mice in each group were dissected 2 h after LPS treatment,and the remaining mice were dissected 18 h after LPS treatment,and serum and kidney were collected.Results As expected,serum BUN and creatinine levels were significantly increased,pathological damage was observed in LPS-treated mice.NAC significantly alleviated LPS-induced reduction of renal function and pathological damage.LPS induced up-regulation of mRNA of renal inflammatory cytokines(Tnfα,Il-6 and Il-1β)and chemokines(Mip2,Kc and Mcp1).NAC treatment obviously against LPS-induced proinflammatory cytokines and chemokines gene expression in kidney tissue.LPS treatment significantly alleviated TNF-αand KC protein expression in mice.NAC treatment significantly inhibited LPS-induced increasing in serum TNF-αand KC protein levels.After LPS treatment,the level of NF-κB p65 protein in kidney was significantly increased,while NAC treatment significantly inhibited LPS-activated NF-κB p65 signaling in kidney.Conclusions NAC alleviates LPS-induced AKI probably through inhibiting NF-κB signaling mediated renal inflammatory response.
作者 黄宣林 赖俊 张祥水 李斌 赖长俊 刘燕 陈远华 Huang Xuanlin;Lai Jun;Zhang Xiangshui;Li Bin;Lai Changjun;Liu Yan;Chen Yuanhua(Shicheng County People's Hospital,Ganzhou,Jiangxi 342700,China;School of Basic Medicine,Anhui Medical University,Hefei,Anhui 230032,China)
出处 《齐齐哈尔医学院学报》 2023年第18期1701-1705,共5页 Journal of Qiqihar Medical University
基金 国家自然科学基金(82173559)。
关键词 细菌脂多糖 N-乙酰半胱氨酸 急性肾损伤 NF-kB信号 Lipopolysaccharide N-acetylcysteine Acute kidney injury NF-κB signaling
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