Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway

Lijun HE; Binbin YANG; Shi ZHUO; Chengzhen GU; Wen DING; Danqi LIU; Xiaomei XU

doi:10.13422/j.cnki.syfjx.20221943

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Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway

更新时间：2022-09-30

- Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 21, Pages: 90-97(2022)
- 作者机构：
  
  1.福建中医药大学附属人民医院，福州 350004
  2.福建农林大学，福州 350002
  3.福建省医学科学研究院福建省医学测试重点实验室，福州 350001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20221943
  CLC： R2-0;R33;R289;R745.1
- Received：04 May 2022，
  
  Published Online：04 August 2022，
  
  Published：05 November 2022
- 稿件说明：
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何丽君,杨彬彬,卓实等.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[J].中国实验方剂学杂志,2022,28(21):90-97.

HE Lijun,YANG Binbin,ZHUO Shi,et al.Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(21):90-97.
何丽君,杨彬彬,卓实等.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[J].中国实验方剂学杂志,2022,28(21):90-97. DOI： 10.13422/j.cnki.syfjx.20221943.

HE Lijun,YANG Binbin,ZHUO Shi,et al.Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(21):90-97. DOI： 10.13422/j.cnki.syfjx.20221943.

摘要

目的

观察淫羊藿苷对阿尔茨海默病（AD）模型大鼠Ras同源基因家族成员A（RhoA）/Rho相关卷曲螺旋形成蛋白激酶（ROCK）信号通路的作用，并探讨其改善神经元和树突损伤的作用机制。

方法

通过对大鼠双侧侧脑室注射

样淀粉蛋白1-42（A

1-42

，

2.5 g·L

-1

）建立AD模型，并将大鼠分为模型组，淫羊藿苷低、中、高剂量组（0.03、0.06、0.09 g·kg

-1

），另设空白组。空白组和模型组按10 mL·kg

-1

的剂量灌胃等体积的生理盐水。采用Morris水迷宫评估大鼠的认知功能。采用尼氏染色观察大鼠海马CA1区病理形态。采用高尔基染色观察大鼠海马CA1区树突棘密度和树突长度。采用实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠海马中肿瘤坏死因子-

（TNF-

）、白细胞介素-1

（IL-1

）、白细胞介素-6（IL-6）、RhoA、ROCK1和ROCK2的mRNA表达水平。采用蛋白免疫印迹法（Western blot）检测大鼠海马中TNF-

、IL-1

、IL-6、RhoA、ROCK1和ROCK2的蛋白表达水平。

结果

与空白组比较，模型组大鼠逃避潜伏期显著增加（

0.01），穿越平台次数和目标象限驻留时间显著减少（

0.01）。与模型组比较，淫羊藿苷中、高剂量组大鼠逃避潜伏期减少（

0.05，

0.01），穿越平台次数和目标象限驻留时间增加（

0.05，

0.01）。与空白组比较，模型组大鼠海马CA1区神经元数量、树突棘密度和树突长度显著减少（

0.01）。与模型组比较，淫羊藿苷中、高剂量组大鼠海马CA1区神经元数量、树突棘密度和树突长度增加（

0.05，

0.01）。与空白组比较，模型组大鼠海马中TNF-

、IL-1

、IL-6、RhoA、ROCK1、ROCK2的mRNA和蛋白表达水平显著升高（

0.01）。与模型组比较，淫羊藿苷中、高剂量组大鼠海马中TNF-

、IL-1

、IL-6、RhoA、ROCK1、ROCK2的mRNA和蛋白表达水平下降（

0.05，

0.01）。

结论

淫羊藿苷改善AD认知功能、神经元和树突损伤可能与抑制RhoA/ROCK信号通路相关。

Abstract

Objective

To 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.

Method

The

-amyloid 1-42 （A

1-42

， 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-

（TNF-

）， interleukin （IL）-1

， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. Western blot assay was used to detect the protein expression levels of TNF-

， IL-1

， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus.

Result

As compared with the control group， the escape latency of the rats in the model group was increased （

0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were decreased （

0.01）. As compared with the model group， the escape latency of the rats in the middle and high-dose icariin groups was decreased （

0.05，

0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were increased （

0.05，

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 （

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 （

0.05，

0.01）. As compared with the control group， the mRNA and protein expression levels of TNF-

， IL-1

， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the model group were increased （

0.01）. As compared with the model group， the mRNA and protein expression levels of TNF-

， IL-1

， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the middle and high-dose icariin groups were decreased （

0.05，

0.01）.

Conclusion

Icariin improves cognitive function and neuronal and dendritic damage in AD by inhibiting the RhoA/ROCK signaling pathway.

关键词

Keywords

references

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