Department of Surgical District 2, Eighth People's Hospital of Dongguan City, Dongguan, China.
Department of Pediatrics, Eighth People's Hospital of Dongguan City, Dongguan, China.
J Biochem Mol Toxicol. 2024 Sep;38(9):e23810. doi: 10.1002/jbt.23810.
Intestinal ischemia-reperfusion (IR) injury is a common gastrointestinal disease that induces severe intestinal dysfunction. Intestinal myenteric neurons participate in maintaining the intestinal function, which will be severely injured by IR. Macrophages are widely reported to be involved in the pathogenesis of organ IR injury, including intestine, which is activated by NLRP3 signaling. Lonicerin (LCR) is a natural extracted monomer with inhibitory efficacy against the NLRP3 pathway in macrophages. The present study aims to explore the potential protective function of LCR in intestinal IR injury. Myenteric neurons were extracted from mice. RAW 264.7 cells were stimulated by H/R with or without 10 μM and 30 μM LCR. Remarkable increased release of IL-6, MCP-1, and TNF-α were observed in H/R treated RAW 264.7 cells, along with an upregulation of NLRP3, cleaved-caspase-1, IL-1β, and EZH2, which were sharply repressed by LCR. Myenteric neurons were cultured with the supernatant collected from each group. Markedly decreased neuron number and shortened length of neuron axon were observed in the H/R group, which were signally reversed by LCR. RAW 264.7 cells were stimulated by H/R, followed by incubated with 30 μM LCR with or without pcDNA3.1-EZH2. The inhibition of LCR on NLRP3 signaling in H/R treated RAW 264.7 cells was abolished by EZH2 overexpression. Furthermore, the impact of LCR on neuron number and neuron axon length in myenteric neurons in the H/R group was abated by EZH2 overexpression. Collectively, LCR alleviated intestinal myenteric neuron injury induced by H/R treated macrophages via downregulating EZH2.
肠缺血再灌注（IR）损伤是一种常见的胃肠道疾病，可导致严重的肠道功能障碍。肠肌间神经元参与维持肠道功能，而 IR 会严重损伤肠肌间神经元。巨噬细胞广泛参与器官 IR 损伤的发病机制，包括肠道，其被 NLRP3 信号激活。毛蕊花糖苷（LCR）是一种天然提取的单体，对巨噬细胞中的 NLRP3 途径具有抑制作用。本研究旨在探讨 LCR 在肠 IR 损伤中的潜在保护作用。从小鼠中提取肌间神经元。用 H/R 刺激 RAW 264.7 细胞，并用或不用 10μM 和 30μM LCR 处理。在 H/R 处理的 RAW 264.7 细胞中观察到显著增加的 IL-6、MCP-1 和 TNF-α释放，以及 NLRP3、裂解半胱天冬酶-1、IL-1β和 EZH2 的上调，这些均被 LCR 显著抑制。用各组上清液培养肌间神经元。在 H/R 组中观察到神经元数量显著减少，神经元轴突长度缩短，LCR 明显逆转了这一现象。用 H/R 刺激 RAW 264.7 细胞，然后用或不用 pcDNA3.1-EZH2 孵育 30μM LCR。EZH2 过表达消除了 LCR 对 H/R 处理的 RAW 264.7 细胞中 NLRP3 信号的抑制作用。此外，EZH2 过表达减弱了 LCR 对 H/R 组肌间神经元中神经元数量和神经元轴突长度的影响。总之，LCR 通过下调 EZH2 缓解了 H/R 处理的巨噬细胞引起的肠肌间神经元损伤。
