目的  探索倍半萜内酯化合物ACT001对鱼藤酮 (ROT) 诱导帕金森病 (PD)模型小鼠神经病理和运动障碍的作用。   方法  SPF级C57BL/6小鼠分为 6 组：完全对照组、溶剂对照组、ROT模型组、ACT001 5 mg/kg 组（ROT+ACT001-5）、ACT001 20 mg/kg 组（ROT+ACT001-20）、左旋多巴（L-dopa）阳性对照组（ROT+L-dopa），每组9只小鼠。完全对照组给予同等剂量的生理盐水腹腔注射；溶剂对照组给予等量的ROT助溶剂但不含ROT；其余各组小鼠均采用腹腔注射ROT的方法建立PD小鼠模型，然后，不同ACT001剂量组小鼠分别腹腔注射相应剂量的ACT001，阳性对照组腹腔注射左旋多巴，连续15 d。采用旷场、转棒、爬杆、平衡木实验检测小鼠行为学变化；免疫荧光(IF)检测小鼠中脑黑质酪氨酸羟化酶(TH)阳性神经元的数量，纹状体TH阳性纤维的含量，小鼠中脑黑质小胶质细胞的活化状态；Real-time PCR检测小鼠中脑肿瘤坏死因子α (TNF-α)、白细胞介素 (IL)-1β、IL-6等炎性因子mRNA的表达水平；Western blotting检测小鼠中脑TH、核因子κB (NF-κB) p65、NF-κB 抑制因子α(IκBα)、磷酸化IκBα (p-IκBα) 等蛋白表达水平。   结果  ROT诱导的PD小鼠模型行为学方面出现运动障碍，中脑黑质中TH阳性神经元数量降低(P ＜0.0001)，纹状体中TH阳性纤维含量降低，中脑黑质中小胶质细胞被激活，TNF-α、IL-1β、IL-6炎性因子的水平及p-IκBα、NF-κB p65蛋白表达上调。ACT001能显著改善ROT模型小鼠行为学障碍及中脑黑质损伤，升高中脑黑质TH阳性神经元的数量，增加纹状体中TH阳性纤维的含量，抑制中脑中黑质小胶质细胞的活化和TH、IκBα 蛋白表达，降低中脑TNF-α、IL-1β、IL-6等炎性因子的表达水平及NF-κB p65、p-IκBα蛋白表达水平(P <0.05)。   结论  ACT001能明显改善ROT诱导的PD小鼠行为障碍，改善多巴胺能神经元丢失现象，抑制中脑黑质小胶质细胞的活化，通过抑制NF-κB信号通路的活化，从而抑制炎症反应。

Objective  To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone (ROT) -induced Parkinson’s disease (PD) model mouse.  Methods  SPF C57BL/6 mice were randomly divided into 6 groups, including control group, solvent control group, ROT model group, ACT001 5 mg/kg group（ROT+ACT001-5）, ACT001 20 mg/kg group（ROT+ACT001-20）, and levodopa(L-dopa) positive control group(ROT+L-dopa)，with 9 mice in each group. The control group received an equivalent amount of intraperitoneal injection of saline, the solvent control group received an equivalent amount of rotenone solvent without rotenone, the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone. Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001, while the positive control group received levodopa intraperitoneally for 15 consecutive days. Behavioral changes in mice were assessed using open field, rotarod, pole-climbing, and balance beam tests. Immunofluorescence (IF) assay to detect the expression of tyrosine hydroxylase (TH) neurons，content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain; Real-time PCR was employed to measure the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) in the substantia nigra of the mouse brain. Western blotting was used to measure the protein levels of TH, nuclear factor-κB (NF-κB) p65, NF-κB inhibitor α (IκBα), and phosphorylated IκBα (p-IκBα) in the substantia nigra of the mouse brain.  Results  Compared to the control group and the solvent control group, the rotenone-induced PD model group exhibited motor impairments in behavioral tests, a decrease in the number of TH positive neurons in the substantia nigra (P <0.0001), decreased levels of TH-positive fibers in the striatum, activation of midbrain substantia microglia，and elevated levels of IL-6,  IL-1β, TNF-α, p-IκBα, and NF-κB p65 expression. ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice, increased the number of TH-positive neurons in the substantia nigra, increased levels of TH-positive fibers in the striatum, inhibition of microglial cell activation in the midbrain substantia nigra, and elevated the protein expression levels of IκBα while reducing the levels of IL-6, IL-1β, TNFα, -IκBα, and NF-κB p65 in the substantia nigra ( P<0.05). At a dose of 5 mg/kg, ACT001 significantly improved behavioral impairments in rotenone-induced PD mice, reduced the loss of dopaminergic neurons, and its mechanism may be related to the inhibition of the NF-κB  signaling pathway and the suppression of inflammation. In summary, the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain, increased the number of TH-positive neurons, and augmented the population of dopaminergic neurons in the substantia nigra, exerting a protective effect on neurons.   Conclusion  ACT001 significantly improves behavioral deficits in ROT-induced PD mice, ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum, inhibits the activation of nigrostriatal microglia in the midbrain, and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway.