Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway
10.13422/j.cnki.syfjx.20221943
- VernacularTitle:淫羊藿苷通过调节RhoA/ROCK信号通路改善AD神经元和树突损伤的机制
- Author:
Lijun HE
1
;
Binbin YANG
1
;
Shi ZHUO
1
;
Chengzhen GU
2
;
Wen DING
2
;
Danqi LIU
2
;
Xiaomei XU
3
Author Information
1. People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine， Fuzhou 350004， China
2. Fujian Agriculture and Forestry University， Fuzhou 350002， China
3. Fujian Provincial Key Laboratory of Medical Testing， Fujian Academy of Medical Sciences， Fuzhou 350001， China
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
icariin;
Ras homolog family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway;
neuronal and dendritic damage
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(21):90-97
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of icariin on the recombinant Ras homolog family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway in rats with Alzheimer's disease （AD）， and to explore the mechanism of icariin in ameliorating the neuronal and dendritic damage. MethodThe β-amyloid 1-42 （Aβ1-42， 2.5 g·L-1） was used to induce AD in rats via lateral ventricle injection， and the rats were divided into a model group， a low-dose icariin group （0.03 g·kg-1）， a middle-dose icariin group （0.06 g·kg-1）， a high-dose icariin group （0.09 g·kg-1）， and a control group. The control group and the model group were given an equal volume of normal saline at a dose of 10 mL·kg-1. The cognitive function of rats was assessed by the Morris water maze. The pathological morphology of the rat hippocampal CA1 area was observed by Nissl staining. Dendritic spine density and dendritic length in the CA1 region of the hippocampus were observed by Golgi-Cox staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. Western blot assay was used to detect the protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. ResultAs compared with the control group， the escape latency of the rats in the model group was increased （P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were decreased （P<0.01）. As compared with the model group， the escape latency of the rats in the middle and high-dose icariin groups was decreased （P<0.05， P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were increased （P<0.05， P<0.01）. As compared with the control group， the number of neurons， dendritic spine density， and dendritic length in the hippocampal CA1 area of the rats in the model group were decreased （P<0.01）. As compared with the model group， the number of neurons， dendritic spine density， and dendritic length in the hippocampus of the rats in the middle and high-dose icariin groups were increased （P<0.05， P<0.01）. As compared with the control group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the model group were increased （P<0.01）. As compared with the model group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the middle and high-dose icariin groups were decreased （P<0.05， P<0.01）. ConclusionIcariin improves cognitive function and neuronal and dendritic damage in AD by inhibiting the RhoA/ROCK signaling pathway.
