Effect of Modified Xiaoyaosan on ERK Signal Transduction Pathway of Dopamine Receptorin Model Rats with Hyperprolactinemia

Lu XU; Yan LI; Fang ZHANG; Jing CHEN

doi:10.13422/j.cnki.syfjx.20191640

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Effect of Modified Xiaoyaosan on ERK Signal Transduction Pathway of Dopamine Receptorin Model Rats with Hyperprolactinemia

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- Effect of Modified Xiaoyaosan on ERK Signal Transduction Pathway of Dopamine Receptorin Model Rats with Hyperprolactinemia
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 15, Pages: 70-76(2019)
- 作者机构：
  
  1.六安市中医院，安徽　六安　 237000；
  2.贵州中医药大学　第一附属医院，贵阳　 550001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191640
  CLC： R2-0; R289; R285.5
- Received：20 December 2018，
  
  Published Online：08 May 2019，
  
  Published：05 August 2019
- 稿件说明：
移动端阅览
Lu XU, Yan LI, Fang ZHANG, et al. Effect of Modified Xiaoyaosan on ERK Signal Transduction Pathway of Dopamine Receptorin Model Rats with Hyperprolactinemia[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 70-76.
DOI：

Lu XU, Yan LI, Fang ZHANG, et al. Effect of Modified Xiaoyaosan on ERK Signal Transduction Pathway of Dopamine Receptorin Model Rats with Hyperprolactinemia[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 70-76. DOI： 10.13422/j.cnki.syfjx.20191640.

摘要

目的：

以疏肝健脾为核心，运用逍遥散加减治疗高泌乳素血症(HPRL)模型大鼠，探讨逍遥散加减对HPRL大鼠模型中枢多巴胺受体细胞外调节蛋白激酶(ERK)信号转导通路的作用机制。

方法：

96只SD雌性大鼠，随机分为正常组，模型组，溴隐亭组(0.001 g·kg

－1

)，逍遥散加减高、中、低剂量组(60，30，15 g·kg

－1

)，多巴胺第一受体(D1R)拮抗剂组(SCH23390组，SCH23390＋逍遥散加减中剂量组，SCH23390＋溴隐亭组)，多巴胺第二受体(D2R)拮抗剂组(氟哌啶醇组，氟哌啶醇组＋逍遥散加减中剂量组，氟哌啶醇组＋溴隐亭组)。采用垂体移植法制作HPRL大鼠模型，给药30 d后，采用蛋白免疫印迹法(Western blot)检测大鼠下丘脑癌蛋白Ras，Raf蛋白的表达；采用实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠下丘脑丝裂原活化蛋白激酶(MAPK)激酶1/2(MEK1/2)mRNA，细胞外信号调节激酶1/2(ERK1/2)mRNA的表达；采用电镜观察卵巢颗粒细胞超微结构。

结果：

与正常组比较，模型组Ras，Raf蛋白，MEK1/2，ERK1/2 mRNA表达显著降低(

0.01)；运用SCH23390拮抗DIR后，与模型组比较，SCH23390组Ras，Raf蛋白，MEK1/2，ERK1/2 mRNA表达有升高趋势，运用氟哌啶醇拮抗D2R后，与模型组比较，氟哌啶醇组Ras，Raf蛋白表达有下降趋势，MEK1/2，ERK1/2 mRNA表达显著下降(

0.01)；运用逍遥散加减治疗后，能显著提高Ras，Raf蛋白，MEK1/2，ERK1/2 mRNA表达(

0.01)，且逍遥散加减高、中剂量组表达增加最明显(

0.01)，效果优于溴隐亭组。电镜下模型组卵巢颗粒细胞形态及线粒体数量、结构异常，运用逍遥散加减治疗后，颗粒细胞形态和线粒体结构趋于正常。

结论：

逍遥散加减通过激动D2R，抑制D1R，调节ERK/MAPK信号通路，并有效改善卵巢颗粒细胞线粒体功能，促进卵泡发育，说明逍遥散加减治疗HPRL是多靶点的作用机制。

Abstract

Objective:

To explore the mechanism of modified Xiaoyaosan on extracellular regulated protein kinase(ERK) signal transduction pathway of central dopamine receptor in hyperprolactinemia(HPRL)model rats by treating them with Shugan Jianpi as the core.

Method:

The 96 SD female rats were randomly divided into normal group

model group

Bromocriptine group (0.001 g·kg

-1

)

modified Xiaoyaosan high

medium and low dose group(60

15 g·kg

-1

)

dopamine D1 receptor(D1R) antagonist group (SCH23390

SCH23390+ modified Xiaoyaosan group

SCH23390+ bromocriptine group)

dopamine D2 receptor(D2R) antagonist group (haloperidol group

haloperidol+ modified Xiaoyaosan group

haloperidol+ bromocriptine group). HPRL rat model was established by pituitary transplanta-tion. After 30 days of administration

renin-angiotensinsystem Ras and Raf protein expressions in thypothalamus of rats were detected by Western blot

and mitogen-activated protein kinase (MAPK) kinase 1/2(MEK1/2)mRNA and extracellular signaling regulates kinase 1/2(ERK1/2) mRNA expressions in the hypothalamus of rats were detected by Real-time PCR.The microstructures of mitochondria in ovarian granulosa cells were observed by electron microscopy.

Result:

The Ras

Raf protein

MEK1/2 and ERK1/2 mRNA expression were significantly decreased in model group compared with normal group (

0.01). After SCH23390 antagonistic DIR was applied

Ras

Raf pprotein

MEK1/2 and ERK1/2 mRNA expression in SCH23390 group showed an increased trend compared with model group

and when haloperidol was used to antagonistic D2R

Ras and Raf expression in haloperidol group showed a decreased trend compared with model group

and MEK1/2 and ERK1/2 mRNA expression significantly decreased(

0.01). The expression of Ras

Raf protein

MEK1/2 and ERK1/2 mRNA was significantly increased after using modified Xiaoyaosan(

0.01)

and the expression was significantly increased in the high and medium-dose groups of prescription(

0.01). The effect was better than that of bromocriptine group.The morphology of granulosa cells and the number and structure of mitochondria in model group were abnormal under electron microscope. After treatment with modified Xiaoyaosan

the morphology and structure of granulosa cells tended to be normal.

Conclusion:

Modified Xiaoyaosan stimulates D2R

inhibits D1R

regulates ERK/MAPK signaling pathway.It also effectively improve the mitochondrial function of ovarian granulosa cells and promote follicular development.It is suggested that the modified Xiaoyaosan with a multi-target mechanism in treating HPRL.

关键词

Keywords

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