School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
Department of Analytical & Testing Center, Nanjing Medical University, Nanjing 211166, PR China.
FEMS Microbiol Lett. 2022 Nov 17;369(1). doi: 10.1093/femsle/fnac103.
Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4/NF-κB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-κB p65, and downstream IκBα were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4/NF-κB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.
急性肾损伤（AKI）是一种具有高发病率和死亡率的全球公共健康危害。脓毒症几乎占 AKI 所有病因的一半。科学家们在探索 AKI 治疗中具有较少副作用的有效治疗药物方面做出了巨大努力，但收效甚微。随着肠道菌群研究的发展，阿克曼氏菌（A. muciniphila）已被证明通过调节炎症反应来预防不同的器官损伤。然而，其肾脏保护作用尚不清楚。在这里，我们使用脂多糖（LPS）在预先用 A. muciniphila 处理或未处理的小鼠中诱导 AKI 模型，测量肾功能和组织学变化。通过 ELISA 和 rt-PCR 检测炎症因子。通过 Western blot 和免疫组化检测 TLR4/NF-κB 信号因子和 NLRP3 炎性体。A. muciniphila 的预处理显著抑制了炎症反应并改善了肾脏组织学变化。此外，模型组中的 TLR4、p-NF-κB p65 和下游 IκBα明显被激活，并被 A. muciniphila 抑制。在 NLRP3 炎性体的调节中也发现了类似的效果。总之，A. muciniphila 的预处理可以通过抑制 TLR4/NF-κB 通路和 NLRP3 炎性体激活来预防 LPS 诱导的 AKI。它可能成为未来 AKI 预防和治疗的一种新的治疗策略。
