Anti-vascular dementia effect of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission
- VernacularTitle: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
- Author:
Yulan FU
1
;
Wei CHEN
2
;
Guifeng ZHUO
1
;
Xiaomin ZHU
1
;
Yingrui HUANG
1
;
Jinzhi ZHANG
1
;
Fucai YANG
1
;
Ying ZHANG
1
;
Lin WU
3
Author Information
1. The First Clinical College，Guangxi University of Chinese Medicine，Nanning 530022，China
2. Dept. of Encephalopathy，Zone 1，the First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530022，China
3. Graduate School，Guangxi University of Chinese Medicine，Nanning 530200，China
- Publication Type:Journal Article
- Keywords:
vascular dementia;
Yifei xuanfei jiangzhuo formula;
mitochondrial fission;
HSP90/MLKL/Drp1 signaling pathway
- From:
China Pharmacy
2025;36(15):1859-1865
- CountryChina
- Language:Chinese
-
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.
