Li Gang, Hu Haiyan
Department of Emergency Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, China.
Department of Emergency, Zhejiang Provincial Hangzhou Emergency Medical Center, Hangzhou, Zhejiang, 310021, China.
BMC Pharmacol Toxicol. 2025 Mar 27;26(1):71. doi: 10.1186/s40360-025-00904-4.
Organophosphorus poisoning (OP), a prevalent form of pesticide intoxication, induces severe multiorgan dysfunction. While combined lipid emulsion (ILE) and standard treatment (pralidoxime methiodide & atropine) demonstrate improved clinical outcomes, the therapeutic mechanisms remain elusive.
An OP rat model was established for: (1) histopathological assessment via hematoxylin-eosin (H&E) staining; (2) LPS/Toll-like receptor 4 (TLR4) quantification through flow cytometry; (3) inflammatory cytokine measurement using enzyme-linked immunosorbent assay (ELISA); and (4) cytokine mRNA analysis via reverse transcription PCR (RT-PCR). TLR4 pathway validation employed anti-TLR4 intervention.
After survived 24 h, multiple organs were damaged in rats with organophosphorus poisoning. Treatment with standard treatment or only lipid emulsion slightly alleviated the symptoms of poisoning, However, when standard treatment was combined with lipid emulsion, the symptoms were significantly alleviated, and the expression level of TLR4 was significantly decreased in the ST + ILE group. After anti-TLR4 was used to block the LPS/TLR4 pathway, liver function and acetylcholinesterase(AchE) levels in rats were significantly improved(P < 0.001), lung and heart pathology improved, and inflammatory cytokines were reduced; Moreover, the expression level of TLR4 in heart and lung also decreased significantly(P < 0.01). As a result, the symptoms of organ poisoning were relieved.
Lipid emulsion is involved in the protective effect via the LPS/TLR4 pathway on vital organs inacute or organophosphorus poisoning.
有机磷中毒（OP）是一种常见的农药中毒形式，可导致严重的多器官功能障碍。虽然联合脂质乳剂（ILE）和标准治疗（碘解磷定和阿托品）显示出更好的临床结果，但其治疗机制仍不清楚。
建立OP大鼠模型用于：（1）通过苏木精-伊红（H&E）染色进行组织病理学评估；（2）通过流式细胞术定量LPS/Toll样受体4（TLR4）；（3）使用酶联免疫吸附测定（ELISA）测量炎性细胞因子；（4）通过逆转录PCR（RT-PCR）进行细胞因子mRNA分析。TLR4通路验证采用抗TLR4干预。
存活24小时后，有机磷中毒大鼠的多个器官受损。标准治疗或仅脂质乳剂治疗可轻微减轻中毒症状，然而，当标准治疗与脂质乳剂联合使用时，症状明显减轻，且ST+ILE组中TLR4的表达水平显著降低。使用抗TLR4阻断LPS/TLR4通路后，大鼠的肝功能和乙酰胆碱酯酶（AchE）水平显著改善（P<0.001），肺和心脏病理学改善，炎性细胞因子减少；此外，心脏和肺中TLR4的表达水平也显著降低（P<0.01）。结果，器官中毒症状得到缓解。
脂质乳剂通过LPS/TLR4通路对急性有机磷中毒的重要器官发挥保护作用。
