目的 探讨洋川芎内酯I（SEN I）调控混合谱系激酶3（MLK3）/ c-Jun氨基末端激酶3（JNK3）信号通路对脓毒症相关性脑病(SAE)大鼠神经元凋亡的影响。    方法  观察经盲肠结扎穿孔术（CLP）制作成功的脓毒症模型大鼠的神经行为学及脑电图改变制作筛选SAE模型。分为正常对照组、假手术组、脓毒症无脑病组、SAE模型组、SAE+ MLK3/JNK3信号通路抑制剂（URMC-099）组、SAE+低剂量SEN I组（36 mg/kg）和SAE+高剂量SEN I组（144 mg/kg），每组10只。模型制作成功 30 min后按组别腹腔注射给药，24 h内完成给药。采用HE染色光学显微镜下观察海马组织病理情况，透射电子显微镜下观察神经元细胞核、胞质形态及线粒体超微结构的改变，TUNEL染色检测海马神经元凋亡，Western blotting检测JNK3、p-JNK3、MLK3、p-MLK3、Fas配体（Fas-L）蛋白的表达水平。    结果 与正常对照组、假手术组比较，脓毒症无脑病组无明显神经元结构形态改变和神经元凋亡，且p-JNK3、JNK3、p-MLK3、MLK3和Fas-L蛋白表达差异均无显著性（P>0.05），而SAE模型组的神经元结构形态损伤加重，神经元凋亡率升高，p-JNK3、JNK3、p-MLK3、MLK3和Fas-L蛋白表达升高（P<0.01）；与SAE模型组比较，抑制剂URMC-099组和SEN I处理组神经元结构形态损伤均明显改善，神经元凋亡率均降低，p-JNK3、JNK3、p-MLK3、MLK3和Fas-L蛋白表达均降低（P<0.01），而高剂量SEN I组更明显。    结论 SEN I通过抑制MLK3/JNK3信号通路活化，有效减轻SAE神经元凋亡，对SAE发挥脑保护作用。

Objective To investigate the effect of senkyunolide I (SEN I) on neuronal apoptosis in sepsis-associated encephalopathy (SAE) rats via modulation of the mixed-lineage kinase 3(MLK3)/c-Jun N-terminal kinase 3(JNK3) signaling pathway.     Methods Screening for a SAE model by monitoring neurobehavioral and electroencephalographic alterations in rats with sepsis induced by cecal ligation and puncture (CLP). Divided into normal control group, sham operation group, sepsis without encephalopathy group, SAE model group, SAE+MLK3/JNK3 signaling pathway inhibitor (URMC-099) group, SAE+lowdose SEN I group (36 mg/kg), and SAE+high-dose SEN I group (144 mg/kg), with 10 animals in each group. After 30 minutes of successful modeling, intraperitoneal injection was administered according to the group, and the administration was completed within 24 hours. HE staining was used to observe the pathological conditions of hippocampal tissue under a light microscope, transmission electron microscopy was used to observe changes in the morphology of neuronal nuclei, cytoplasm, and mitochondrial ultrastructure, TUNEL staining was used to detect hippocampal neuronal apoptosis, and Western blotting was used to detect the expression levels of p -JNK3, JNK3, p-MLK3, MLK3, and Fas ligand （Fas-L）proteins. Results Compared with the normal control group and sham surgery group, the sepsis without encephalopathy group showed no significant changes in neuronal structural morphology and neuronal apoptosis, and there were no significant differences in the expression of p-JNK3, JNK3, p-MLK3, MLK3, and Fas-L proteins (P>0.05). However, the SAE model group had aggravated neuronal structural morphology damage, increased neuronal apoptosis rate, and increased expression level of p-JNK3, JNK3, p-MLK3, MLK3, and Fas-L proteins (P<0.01); Compared with the SAE model group, the inhibitor URMC-099 and SEN I treatment groups showed significant improvement in neuronal structural and morphological damage, decreased neuronal apoptosis rates, and reduced p-JNK3, JNK3, p-MLK3, MLK3, and Fas-L protein expression (P<0.01), with the highdose SEN I group showing more significant improvement.   Conclusion SEN I effectively reduces neuronal apoptosis in SAE and exerts neuroprotective effects on SAE by inhibiting the activation of the MLK3/JNK3 signaling pathway.