水苏碱调节CCL2-CCR2信号通路对血管性痴呆大鼠神经炎症的影响

Effect of stachydatine on neuroinflammation in vascular dementia rats by regulating the CCL2-CCR2 signaling pathway

关键词:  血管性痴呆  神经炎症  水苏碱  CC趋化因子配体2-CC趋化因子受体2信号通路

Key words:  Vascular dementia  Neuroinflammation  Stachydrine  CC chemokine ligand 2-CC chemokine receptor 2 signaling pathway

摘要:

目的：探究水苏碱（STA）调节CC趋化因子配体2（CCL2）-CC趋化因子受体2（CCR2）信号通路对血管性痴呆（VD）大鼠神经炎症的影响。方法：采用双侧颈总动脉闭塞手术构建VD大鼠模型，将大鼠分为假手术组、VD组、STA低剂量组、STA中剂量组、STA高剂量组，Morris水迷宫实验检测各组大鼠认知功能，HE染色观察海马组织病理改变，Nissl染色观察海马组织神经元损伤，免疫荧光观察海马组织小胶质细胞活化，ELISA检测海马组织IL-6、TNF-α、IL-8水平，Western blot检测蛋白表达IL-6、TNF-α、CCL2、CCR2蛋白表达。结果：与假手术组比，VD组大鼠海马组织神经元排列紊乱，神经元细胞损伤，逃避潜伏期、Iba1阳性细胞数、IL-6、TNF-α、IL-8水平及IL-6、TNF-α、CCL2、CCR2蛋白表达显著增加，穿越平台次数、Nissl体数量显著减少（P＜0.05）；与VD组相比，STA低、中、高剂量组海马组织神经元排列整齐，神经元细胞恢复，逃避潜伏期、Iba1阳性细胞数、IL-6、TNF-α、IL-8水平及IL-6、TNF-α、CCL2、CCR2蛋白表达显著降低，穿越平台次数、Nissl体数量显著增加，且STA高剂量组改善效果最为显著（P＜0.05）。结论：STA能改善VD大鼠神经元损伤，减少神经炎症，可能与抑制CCL2-CCR2信号通路有关。

Abstract:

Objective: To investigate the effect of stachydatine (STA) on neuroinflammation in vascular dementia (VD) rats by regulating the CC chemokine ligand 2 (CCL2) - CC chemokine receptor 2 (CCR2) signaling pathway. Methods: A VD rat model was constructed using bilateral carotid artery occlusion surgery. The rats were separated into sham surgery group, VD group, low-dose STA group, medium-dose STA group, and high-dose STA group, Morris water maze experiment was applied to detect cognitive function of rats in each group, HE staining was applied to observe pathological changes in hippocampal tissue, Nissl staining was applied to observe neuronal damage in hippocampal tissue, immunofluorescence was applied to observe the activation of microglia in hippocampal tissue, ELISA was applied to detect the levels of IL-6, TNF-α, and IL-8 in hippocampal tissue, Western blot was applied to detect protein expression of IL-6, TNF-α, CCL2, and CCR2. Results: Compared with the sham surgery group, the neurons in the hippocampus of rats in the VD group were disordered and damaged, the escape latency, number of Iba1 positive cells, levels of IL-6, TNF-α, IL-8, and expression of IL-6, TNF-α, CCL2, and CCR2 proteins obviously increased, the number of crossing platforms and the number of Nissl bodies obviously decreased (P<0.05); compared with the VD group, the hippocampal neurons in the low, medium, and high dose groups of STA were arranged neatly, and the neuronal cells recovered, the escape latency, number of Iba1 positive cells, levels of IL-6, TNF-α, IL-8, and expression of IL-6, TNF-α, CCL2, and CCR2 proteins obviously decreased, the number of crossing platforms and the number of Nissl bodies obviously increased, and the high-dose STA group had the most obvious improvement effect (P<0.05). Conclusion: STA can improve neuronal damage and reduce neuroinflammation in VD rats, which may be related to the inhibition of the CCL2-CCR2 signaling pathway.