利拉鲁肽对百草枯诱导的小鼠帕金森病模型炎症及线粒体融合/分裂的影响

doi:10.16098/j.issn.0529-1356.2023.06.008

摘要/Abstract

摘要：

目的探讨利拉鲁肽对百草枯（PQ）诱导的帕金森病（PD）小鼠模型保护作用以及作用机制。方法 24只昆明种小鼠随机分为对照组、PQ组、PQ +利拉鲁肽组，每组8只。通过连续5 d腹腔注射PQ (10 mg/kg)复制PD小鼠模型，连续7 d腹腔注射利拉鲁肽(50 nmol/kg)进行干预。采用行为学方法检测小鼠自主活动能力；免疫荧光观察酪氨酸羟化酶（TH）、离子钙接头蛋白分子1（Iba1）阳性细胞数；Western blotting检测TH、胶质纤维酸性蛋白（GFAP）、线粒体融合基因2（Mfn2）、线粒体动力相关蛋白1（Drp1）蛋白的表达。结果与对照组相比，PQ组站立次数极显著减少（P<0.01），活动次数显著减少（P<0.05），黑质TH阳性细胞数、TH蛋白表达极显著减少(P<0.01)，Iba1阳性细胞数、GFAP蛋白表达极显著增加(P<0.01)，Drp1蛋白表达显著增加(P<0.05)，Mfn2蛋白表达显著降低(P<0.05)。经利拉鲁肽干预后，与对照组相比，PQ +利拉鲁肽组TH阳性细胞数显著降低(P<0.05)；与PQ组相比，PQ +利拉鲁肽组小鼠站立次数、活动次数显著增加(P<0.05)，TH阳性细胞数、TH蛋白表达极显著增加(P<0.01)，Iba1阳性细胞数极显著减少(P<0.01)，GFAP蛋白表达显著减少(P<0.05)，Drp1蛋白表达极显著减少(P<0.01)，Mfn2蛋白表达极显著增加(P<0.01)。结论利拉鲁肽能减轻PQ诱导的PD模型小鼠黑质神经炎症，调节线粒体融合、分裂，减少多巴胺能神经元的丢失，具有神经保护作用。

关键词: 帕金森病, 利拉鲁肽, 百草枯, 炎症, 线粒体融合/分裂, 免疫荧光, 免疫印迹法, 小鼠

Abstract:

Objective To investigate the protective effect and mechanism of liraglutide on the paraquat (PQ)-induced Parkinson’s disease (PD) mouse model. Methods Totally 24 Kunming mice were randomly divided into control group, PQ group and PQ +liraglutide group, 8 mice in each group. PD model was established by intraperitoneal injection of PQ (10 mg/kg) for 5 consecutive days, and liraglutide (50 nmol/kg) was injected intraperitoneally for 7 consecutive days. The free-standing and locomotor activity of mice were measured by behavioral method. Immunofluorescence was used to observe the number of tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive cells. Western blotting was used to detect the expression of protein TH, glial fibrillary acidic protein (GFAP), mitofusin-2 (Mfn2) and dynamin-related protein 1 (Drp1). Results The numbers of free-standing and locomotor activity numbers decreased significantly (P<0.01, P<0.05) in PQ group compared with the control group, and the number of TH immunoreactive cells and TH protein expression in substantia nigra decreased significantly (P<0.01, P<0.01) compared with the control group, while the number of Iba1 immunoreactive cells and GFAP protein expression increased significantly (P<0.01, P<0.01) compared with the control group; the expression of Drp1 protein in PQ group was significantly higher than that in control group (P<0.05), while the Mfn2 protein expression decreased significantly (P<0.05) compared with the control group. After treatment with liraglutide, the number of TH positive cells in PQ + liraglutide group was significantly lower than that in control group (P<0.05); the numbers of free-standing and locomotor activity increased significantly (P<0.05, P<0.05) in PQ + liraglutide group compared with the PQ group, and the number of TH positive cells and expression of TH protein in PQ + liraglutide group were significantly higher than that in PQ group (P<0.01, P<0.01); while the number of Iba1 positive cells and GFAP protein expression decreased significantly (P<0.01, P<0.05) compared with the PQ group; the Drp1 protein expression decreased significantly (P<0.01) compared with the PQ group, while the expression of Mfn2 protein in PQ + liraglutide group was significantly higher than that in PQ group (P<0.01). Conclusion Liraglutide has neuroprotective effect by reducing neuroinflammation in substantia nigra, regulating mitochondrial fusion and fission.

Key words: Parkinson’s disease, Liraglutide, Paraquat, Inflammation, Mitochondrial fusion/division, Immunofluorescence, Western blotting, Mouse

中图分类号:

R742. 5

刘哲川李坤马帅男孟家琪王艳芹.

利拉鲁肽对百草枯诱导的小鼠帕金森病模型炎症及线粒体融合/分裂的影响 [J]. 解剖学报, 2023, 54(6): 676-681.

LIU Zhe-chuan LI Kun MA Shuai-nan MENG Jia-qi WANG Yan-qin. Effects of liraglutide on inflammation and mitochondrial fusion/division in Parkinson’s disease model of mice induced by paraquat[J]. Acta Anatomica Sinica, 2023, 54(6): 676-681.

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