Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3884-3890. doi: 10.3892/mmr.2017.8332. Epub 2017 Dec 20.
As microglial activation is a key factor in the pathogenesis of Parkinson's disease (PD), drugs that target this process may help to prevent or delay the development of PD. The present study investigated the effects of dl‑3‑n‑butylphthalide (NBP) on microglia in a lipopolysaccharide (LPS)-induced PD mouse model. The mice were randomly divided into a blank control group, LPS control group and NBP + LPS treatment group. Mice in the treatment group were given an intragastric infusion of 120 mg/kg NBP daily for 30 days during the establishment of the PD mouse model. At 4 and 28 weeks post‑treatment, the motor behaviours of the mice in each group were observed using the rotarod test and the open field test. In addition, immunohistochemical staining was performed to determine the levels of activated microglia, tumour necrosis factor‑α and α‑synuclein, and the number of tyrosine hydroxylase (TH)‑positive cells in the substantia nigra. NBP significantly improved dyskinesia, reduced microglial activation, decreased nuclear α‑synuclein deposition and increased the survival of TH‑positive cells in the substantia nigra of LPS‑induced PD model mice. These findings suggested that NBP may exert its therapeutic effect by reducing microglial activation in a mouse model of PD.
由于小胶质细胞激活是帕金森病 (PD) 发病机制中的一个关键因素,因此针对该过程的药物可能有助于预防或延迟 PD 的发展。本研究探讨了 dl-3-n-丁基苯酞 (NBP) 对脂多糖 (LPS) 诱导的 PD 小鼠模型中小胶质细胞的影响。将小鼠随机分为空白对照组、LPS 对照组和 NBP+LPS 治疗组。治疗组小鼠在 PD 小鼠模型建立期间每天给予 120mg/kg NBP 灌胃 30 天。在治疗后 4 周和 28 周,通过转棒试验和旷场试验观察每组小鼠的运动行为。此外,通过免疫组织化学染色来确定激活的小胶质细胞、肿瘤坏死因子-α和α-突触核蛋白的水平,以及黑质中酪氨酸羟化酶 (TH)阳性细胞的数量。NBP 可显著改善运动障碍,减少小胶质细胞激活,减少核α-突触核蛋白沉积,并增加 LPS 诱导的 PD 模型小鼠黑质中 TH 阳性细胞的存活。这些发现表明,NBP 可能通过减少 PD 小鼠模型中小胶质细胞的激活发挥其治疗作用。