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-α levels 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-α levels 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.
