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Abstract：
UNASSIGNED: Previous studies of our research group have shown that Chuanxiong Renshen Decoction (CRD) has the effect of treating AD, but the exact mechanism of its effect is still not clarified. The aim of this study was to investigate the effect and mechanism of CRD on AD neuroinflammation.
UNASSIGNED: Morris Water Maze (MWM) tests were employed to assess the memory and learning capacity of AD mice. HE and Nissl staining were used to observe the neural cells of mice. The expression of Iba-1 and CD86 were detected by immunohistochemical staining. Utilize UHPLC-MS/MS metabolomics techniques and the KEGG to analyze the metabolic pathways of CRD against AD. Lipopolysaccharide (LPS) induced BV2 microglia cells to construct a neuroinflammatory model. The expression of Iba-1 and CD86 were detected by immunofluorescence and flow cytometry. The contents of TNF-α and IL-1β were detected by ELISA. Western blot assay was used to detect the expression of PPARγ, p-NF-κB p65, NF-κB p65 proteins and inflammatory cytokines iNOS and COX-2 in PPARγ/NF-κB pathway with and without PPARγ inhibitor GW9662.
UNASSIGNED: CRD ameliorated the learning and memory ability of 3×Tg-AD mice, repaired the damaged nerve cells in the hippocampus, reduced the area of Iba-1 and CD86 positive areas in both the hippocampus and cortex regions, as well as attenuated serum levels of IL-1β and TNF-α in mice. CRD-containing serum significantly decreased the expression level of Iba-1, significantly reduced the levels of TNF-α and IL-1β, significantly increased the protein expression of PPARγ, and significantly decreased the proteins expression of iNOS, COX-2 and p-NF-κB p65 in BV2 microglia cells. After addition of PPARγ inhibitor GW9662, the inhibitory effect of CRD-containing serum on NF-κB activation was significantly weakened.
UNASSIGNED: CRD can activate PPARγ, regulating PPARγ/NF-κB signaling pathway, inhibiting microglia over-activation and reducing AD neuroinflammation.
UNASSIGNED: Morris Water Maze (MWM) tests were employed to assess the memory and learning capacity of AD mice. HE and Nissl staining were used to observe the neural cells of mice. The expression of Iba-1 and CD86 were detected by immunohistochemical staining. Utilize UHPLC-MS/MS metabolomics techniques and the KEGG to analyze the metabolic pathways of CRD against AD. Lipopolysaccharide (LPS) induced BV2 microglia cells to construct a neuroinflammatory model. The expression of Iba-1 and CD86 were detected by immunofluorescence and flow cytometry. The contents of TNF-α and IL-1β were detected by ELISA. Western blot assay was used to detect the expression of PPARγ, p-NF-κB p65, NF-κB p65 proteins and inflammatory cytokines iNOS and COX-2 in PPARγ/NF-κB pathway with and without PPARγ inhibitor GW9662.
UNASSIGNED: CRD ameliorated the learning and memory ability of 3×Tg-AD mice, repaired the damaged nerve cells in the hippocampus, reduced the area of Iba-1 and CD86 positive areas in both the hippocampus and cortex regions, as well as attenuated serum levels of IL-1β and TNF-α in mice. CRD-containing serum significantly decreased the expression level of Iba-1, significantly reduced the levels of TNF-α and IL-1β, significantly increased the protein expression of PPARγ, and significantly decreased the proteins expression of iNOS, COX-2 and p-NF-κB p65 in BV2 microglia cells. After addition of PPARγ inhibitor GW9662, the inhibitory effect of CRD-containing serum on NF-κB activation was significantly weakened.
UNASSIGNED: CRD can activate PPARγ, regulating PPARγ/NF-κB signaling pathway, inhibiting microglia over-activation and reducing AD neuroinflammation.
摘要：
■本课题组前期研究表明，川芎人参汤（CRD）具有治疗AD的作用，但其作用的确切机制尚不清楚。本研究旨在探讨CRD在AD神经炎症中的作用及其机制。
Morris水迷宫(MWM)测试用于评估AD小鼠的记忆和学习能力。HE和Nissl染色观察小鼠神经细胞。免疫组化染色检测Iba-1和CD86的表达。利用UHPLC-MS/MS代谢组学技术和KEGG分析CRD抗AD的代谢途径。脂多糖(LPS)引诱BV2小胶质细胞构建神经炎模子。免疫荧光和流式细胞术检测Iba-1和CD86的表达。ELISA法检测TNF-α和IL-1β的含量。Westernblot法检测PPARγ的表达,p-NF-κBp65，NF-κBp65蛋白和炎症细胞因子iNOS和COX-2在PPARγ/NF-κB途径中有或没有PPARγ抑制剂GW9662。
■CRD改善了3×Tg-AD小鼠的学习记忆能力，修复了海马中受损的神经细胞,减少了海马和皮质区域Iba-1和CD86阳性区域的面积，以及降低小鼠血清IL-1β和TNF-α水平。含CRD的血清中Iba-1的表达水平明显降低,TNF-α和IL-1β水平明显降低,显著增加PPARγ的蛋白表达，显著降低了iNOS的蛋白表达,BV2小胶质细胞的COX-2和p-NF-κBp65。添加PPARγ抑制剂GW9662后，含CRD的血清对NF-κB活化的抑制作用明显减弱。
■CRD可以激活PPARγ，调节PPARγ/NF-κB信号通路,抑制小胶质细胞过度激活并减少AD神经炎症。
Morris水迷宫(MWM)测试用于评估AD小鼠的记忆和学习能力。HE和Nissl染色观察小鼠神经细胞。免疫组化染色检测Iba-1和CD86的表达。利用UHPLC-MS/MS代谢组学技术和KEGG分析CRD抗AD的代谢途径。脂多糖(LPS)引诱BV2小胶质细胞构建神经炎模子。免疫荧光和流式细胞术检测Iba-1和CD86的表达。ELISA法检测TNF-α和IL-1β的含量。Westernblot法检测PPARγ的表达,p-NF-κBp65，NF-κBp65蛋白和炎症细胞因子iNOS和COX-2在PPARγ/NF-κB途径中有或没有PPARγ抑制剂GW9662。
■CRD改善了3×Tg-AD小鼠的学习记忆能力，修复了海马中受损的神经细胞,减少了海马和皮质区域Iba-1和CD86阳性区域的面积，以及降低小鼠血清IL-1β和TNF-α水平。含CRD的血清中Iba-1的表达水平明显降低,TNF-α和IL-1β水平明显降低,显著增加PPARγ的蛋白表达，显著降低了iNOS的蛋白表达,BV2小胶质细胞的COX-2和p-NF-κBp65。添加PPARγ抑制剂GW9662后，含CRD的血清对NF-κB活化的抑制作用明显减弱。
■CRD可以激活PPARγ，调节PPARγ/NF-κB信号通路,抑制小胶质细胞过度激活并减少AD神经炎症。
