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益肺宣肺降浊方通过抑制线粒体分裂抗血管性痴呆的作用研究
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| 篇名： | 益肺宣肺降浊方通过抑制线粒体分裂抗血管性痴呆的作用研究 |
| TITLE： | Anti-vascular dementia effect of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission |
| 摘要： | 目的 探究益肺宣肺降浊方通过抑制线粒体分裂对血管性痴呆（VaD）大鼠的干预作用及其潜在机制。方法采用双侧颈总动脉结扎法建立VaD大鼠模型。将实验动物随机分为假手术组（SHAM组）、模型组（MOD组）、益肺宣肺降浊方低剂量组、益肺宣肺降浊方高剂量组、盐酸多奈哌齐组（阳性对照），每组9只。干预30d后，通过Morris水迷宫实验评估大鼠的学习及空间记忆能力；苏木精-伊红染色观察海马CA1区组织病理学变化；酶联免疫吸附试验法检测血清中炎症因子[白细胞介素（IL）-1β、IL-4]水平；Westernblot法检测海马组织中热休克蛋白90（HSP90）/混合谱系激酶结构域样蛋白（MLKL）/动力相关蛋白1（Drp1）信号通路相关蛋白、线粒体融合蛋白（MFN1、MFN2）及三磷酸腺苷合成酶5A（ATP5A）的蛋白表达；免疫组化检测磷酸化MLKL（p-MLKL）水平；实时荧光定量PCR检测HSP90、MFN1、MFN2、ATP5A的mRNA表达。结果与SHAM组比较，MOD组大鼠逃避潜伏期显著延长，穿越平台次数显著减少，海马组织呈现典型神经元损伤特征，p-MLKL阳性表达量及血清中IL-1β水平均显著升高，血清中IL-4水平显著降低，海马组织中HSP90蛋白及mRNA、p-MLKL/MLKL及p-Drp1（Ser616）/Drp1蛋白表达水平均显著上调，MFN1、MFN2、ATP5A蛋白及mRNA和p-Drp1（Ser637）/Drp1蛋白表达水平均显著下调（P＜0.05）。经益肺宣肺降浊方干预后，各给药组上述指标水平均显著逆转（P＜0.05）。结论益肺宣肺降浊方可能通过调控HSP90/MLKL/Drp1信号通路，抑制线粒体分裂，进而维持线粒体动力学平衡，改善线粒体功能，从而起到减轻VaD大鼠的神经元损伤和神经炎症反应的作用。 |
| ABSTRACT： | OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function. |
| 期刊： | 2025年第36卷第15期 |
| 作者： | 符钰岚；陈炜；卓桂锋；朱小敏；黄颖睿；张金枝；杨富才；张颖；吴林 |
| AUTHORS： | FU Yulan，CHEN Wei， ZHUO Guifeng，ZHU Xiaomin，HUANG Yingrui，ZHANG Jinzhi，YANG Fucai，ZHANG Ying，WU Lin |
| 关键字： | 血管性痴呆；益肺宣肺降浊方；线粒体分裂；HSP90/MLKL/Drp1信号通路 |
| KEYWORDS： | vascular dementia； Yifei xuanfei jiangzhuo formula； mitochondrial fission； HSP90/MLKL/Drp1 signaling pathway |
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