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白介素-1受体相关激酶在重症腹内感染大鼠肝脏损伤中的机制研究及中药的干预作用

Mechanistic studies of IRAK-4 during hepatic injuries and intervention effects of Chinese herbal medicine in a rat model of severe intra-abdominal infections
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摘要 目的:探讨白介素-1受体相关激酶(IRAK-4)在重症腹内感染大鼠肝损伤的作用机制,以及通里攻下方剂的治疗作用。方法:通过建立大鼠重症腹内感染模型,并随机分为假手术组、模型组和中药治疗组。每组分3、6、12、24h 4个时间亚组,检测每组肝脏组织IRAK-4蛋白表达水平、门静脉内毒素水平及血浆肿瘤坏死因子-α(TNF-α)含量,观察肝组织HE染色结果。结果:模型组和中药治疗组在造模后各个时间点IRAK-4蛋白表达水平较假手术组均明显升高(P<0.05);中药治疗组与模型组比较,在24h时显著降低(P<0.05);模型组肝脏IRAK-4蛋白表达水平与门静脉内毒素变化、血浆TNF-α含量呈正相关。结论:IRAK-4蛋白表达水平升高可能是内毒素信号传导通路导致肝脏损伤的重要因素;通里攻下方剂可抑制IRAK-4激酶活性,减轻重症腹内感染大鼠肝脏损伤的程度。 Objective: To discuss the underlying mechanisms during hepatic injuries and explore the therapeutic effects of dispelling and purgation formula in a rat model of severe intra-abdominal infections. Methods: The severe intra-abdominal infection model was established. The animals were randomly divided into three groups: sham surgery (Group S), model (Group M) and TCM treatment (Group T). And each group was further divided into 4 timepoint sub-groups of 3, 6, 12 and 24h. The expression level of hepatic IRAK-4 protein was measured, the levels of endotoxin in portal vein, and the plasma content of tumor necrosis factor-alpha (TNF-α) were detected. The hematoxylin & eosin staining slides of hepatic tissues were observed. Results: Compared with Group S, the expression levels of IRAK-4 protein at each timepoint post-modeling in both Groups M and T had markedly elevated (P〈0.05). Group T decreased markedly at 24h compared with Group M (P〈0.05); the expression level of hepatic IRAK-4 protein in Group M was positively correlated with the changes of endotoxin in portal vein and the plasma content of TNF-α. Conclusion: The up-regulated expression level of IRAK-4 protein may be an important contributing factor of signal transduction pathway of endotoxin to hepatic injuries. The formula of dispelling and purgation may suppress the activities of IRAK-4 kinase and alleviate the hepatic injury extents of severe intra-abdominal infections.
出处 《中华中医药杂志》 CAS CSCD 北大核心 2014年第1期292-295,共4页 China Journal of Traditional Chinese Medicine and Pharmacy
关键词 内毒素 肝损伤 白介素一1受体相关激酶 通里攻下方剂 肿瘤坏死因子-α Endotoxin Liver injury IRAK-4 Tongli Gongxia Formulae Tumor necrosis factor-α
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