TLR4/Myd88/NF-κB通路介导表没食子儿茶素没食子酸酯对脓毒血症大鼠急性肾损伤的保护作用  

Protective Effect of Epigallocatechin Gallate on Acute Kidney Injury Induced by Lipopolysaccharide in Rats via TLR4/Myd88/NF-κB Pathway

作　　者：李木子 陈克研 孙倩 邱雨华 LI Muzi;CHEN Keyan;SUN Qian;QIU Yuhua(Department of Nephrology,Liaoning Golden Autumn Hospital,Shenyang 110016,China;Department of Laboratory Animal Science,China Medical University,Shenyang 110122,China)

机构地区：[1]辽宁省金秋医院肾内科,沈阳110016 [2]中国医科大学实验动物部,沈阳110122

出　　处：《中国医科大学学报》2019年第2期109-113,共5页Journal of China Medical University

基　　金：国家自然科学基金青年科学基金(31201758)

摘　　要：目的观察表没食子儿茶素没食子酸酯(EGCG)对脂多糖(LPS)诱导大鼠急性肾损伤(AKI)的保护作用及TLR4/Myd88/核因子kappa B (NF-κB)的作用机制。方法将SD大鼠随机分为假手术组(Sham组)、LPS诱导急性肾损伤组(AKI组)、EGCG治疗组(EGCG组)和EGCG+LPS+TLR4抑制剂组(TLR4组),每组10只。建立内毒素血症大鼠模型,检测血清肌酐(Cr)和尿素氮(BUN)的变化;ELISA检测血清中白细胞介素-6 (IL-6)、白细胞介素-1β(IL-1β)、白细胞介素-10 (IL-10)和肿瘤坏死因子-α(TNF-α)水平;HE检测肾脏病理组织学变化,Western blotting和实时PCR检测大鼠肾脏中TLR4、Myd88和NF-κB蛋白及m RNA表达。结果与Sham组相比,AKI组大鼠肾脏损伤明显,血清中Cr、BUN及促炎性细胞因子水平显著升高,IL-10水平显著降低,TLR4、Myd88和NF-κB蛋白及mRNA表达显著升高;而在建模前给予EGCG可以改善AKI,明显降低炎性细胞因子表达,降低TLR4、Myd88和NF-κB表达;给予TLR4抑制剂后,EGCG对AKI的保护作用受到抑制。结论 EGCG对LPS导致的AKI具有保护作用,其机制可能与抑制TLR4/Myd88/NF-κB通路的激活有关。Objective To evaluate the protective effect of epigallocatechin gallate(EGCG)on lipopolysaccharide(LPS)-induced acute kidney injury(AKI)in rats and its underlying mechanisms.Methods Sprague-Dawley rats were randomly divided into the Sham group,AKI group,EGCG group and TLR4 group(n=10 each).To establish the rat model of endotoxemia,serum creatinine(Cr)and urea nitrogen(BUN)levels were detected by biochemical assays;serum interlukin(IL)-6,IL-1β,IL-10,and TNF-αlevels were detected by ELISA;kidney histopathology was examined by hematoxylin and eosin(HE)staining method;and expression of TLR4,Myd88 and nuclear factor-kappa B(NF-κB)in rat kidneys at both protein and mRNA levels was detected by Western blotting and qRT-PCR,respectively.Results Kidney injury increased significantly in AKI group compared to the sham group.Serum Cr,BUN,IL-6,IL-1β,and TNF-αlevels significantly increased whereas IL-10 levels significantly decreased in AKI group compared to the sham group.Expression levels of TLR4,Myd88,and NF-κB also significantly increased at both protein and mRNA levels in AKI group compared to the sham group.Treatment with EGCG prior to induction of LPS-mediated AKI conferred protection against AKI by significantly reducing the expression of inflammatory markers such as,TLR4,Myd88,and NF-κB.Given TLR4 inhibitor based on this,the protective effect of EGCG on AKI was via inhibition of the TLR4/Myd88/NF-κB pathway.Conclusion EGCG exhibited a protective effect against LPS-induced AKI by inhibiting the activation of TLR4/Myd88/NF-κB pathway.

关 键 词：表没食子儿茶素没食子酸酯 急性肾损伤 TLR4 核因子KAPPA B 脂多糖 

分 类 号：R34[医药卫生—基础医学]