Effect of Buyang Huanwu Tang on Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats Based on PI3K/Akt/eNOS Signaling Pathway

Ru WANG; Lei ZHANG; Wei-pin LI; Yan-fang SHEN; Ju-mei DU

doi:10.13422/j.cnki.syfjx.20191136

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Effect of Buyang Huanwu Tang on Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats Based on PI3K/Akt/eNOS Signaling Pathway

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Buyang Huanwu Tang on Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats Based on PI3K/Akt/eNOS Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 13, Pages: 22-27(2019)
- 作者机构：
  
  陕西中医药大学　第二附属医院，陕西　咸阳　 712000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191136
  CLC： R289; R743; R973+ .6
- Received：20 December 2018，
  
  Published Online：19 February 2019，
  
  Published：05 July 2019
- 稿件说明：
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Ru WANG, Lei ZHANG, Wei-pin LI, et al. Effect of Buyang Huanwu Tang on Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats Based on PI3K/Akt/eNOS Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 22-27.
DOI：

Ru WANG, Lei ZHANG, Wei-pin LI, et al. Effect of Buyang Huanwu Tang on Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats Based on PI3K/Akt/eNOS Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 22-27. DOI： 10.13422/j.cnki.syfjx.20191136.

摘要

目的：

探讨补阳还五汤改善蛛网膜下腔出血后脑血管痉挛的相关分子机制。

方法：

将雄性SD大鼠80只随机分为假手术组、模型组、补阳还五汤低、高剂量组(13，26 g·kg

－1

·d

－1

)，每组20只。按照10 mL·kg

－1

每天灌胃给药2次，连续7 d。采用二次枕大池注血法制作蛛网膜下腔出血模型，评估各组大鼠1，3，5，7 d的神经功能评分，利用苏木素-伊红(HE)染色对各组大鼠基底动脉直径进行测量，蛋白免疫印迹法(Western blot)检测基底动脉脑组织磷酸化磷脂酰肌醇3-激酶(p-PI3K)，磷酸化蛋白激酶B(p-Akt)，内皮型一氧化氮合酶(eNOS)，神经型一氧化氮合酶(nNOS)蛋白的表达；酶联免疫吸附测定(ELISA)检测大鼠脑脊液中一氧化氮(NO)，内皮素-1(ET-1)的表达。

结果：

与假手术组比较，模型组大鼠神经功能评分明显下降(

0.05)，基底动脉直径明显缩小(

0.05)，基底动脉脑组织p-PI3K，p-Akt，eNOS，nNOS蛋白的表达明显降低(

0.05)，脑脊液中NO明显减少(

0.05)，ET-1明显升高(

0.05)；与模型组比较，不同剂量补阳还五汤组(26，13 g·kg

－1

·d

－1

)在治疗后3～5 d后大鼠神经功能评分均有不同程度升高，基底动脉直径明显增宽(

0.05)，p-PI3K，p-Akt，eNOS蛋白的表达明显升高(

0.05)，NO明显升高(

0.05)，ET-1明显下降(

0.05)；与低剂量组比较，经过7 d的补阳还五汤治疗后高剂量组神经功能评分明显升高(

0.05)，基底动脉直径增宽更明显(

0.05)，p-PI3K，p-Akt，eNOS蛋白的表达更高(

0.05)，NO升高更明显(

0.05)，ET-1下降更明显(

0.05)。

结论：

补阳还五汤对蛛网膜下腔出血后脑血管痉挛的保护作用可能与上调PI3K/Akt/eNOS信号通路中的p-PI3K，p-Akt，eNOS的表达，从而增加NO产生有关。

Abstract

Objective:

To investigate the molecular mechanism of Buyang Huanwu Tang in improving cerebral vasospasm after subarachnoid hemorrhage.

Method:

Eighty male Sprague-Dawley rats were randomly divided into sham operation group

model group

Buyang Huanwu Tang low and high dose (13

26 g·kg

-1

·d

-1

) group. According to 10 mL·kg

-1

the drug was administered twice a day for 7 days. The subarachnoid hemorrhage model was made by double occipital pool injection method. The neurological function scores of rats in each group were evaluated at 1

5 and 7 days. The diameter of basilar artery was measured by hematoxylin-eosin (HE)staining. The expressions of phosphp-phosphoinositide 3-kinases(p-PI3K)

phosphp-protein kinase B(p-Akt)

endothelial nitric oxide synthase(eNOS) and neuronal nitric oxide synthase(nNOS) protein in basilar artery brain tissue were detected by Western blot. The expression of nitric oxide(NO) and endothelin-1(ET-1) in rat cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA).

Result:

Compared with sham operation group

the neurological function scores of the model group were significantly decreased (

0.05)

the diameter of the basilar artery was significantly reduced (

0.05)

and The expression of p-PI3K

p-Akt

eNOS

nNOS proteins of the basilar artery brain tissue were significantly decreased (

0.05). The level of NO in the cerebrospinal fluid was significantly decreased (

0.05)

and the ET-1 was significantly increased (

0.05). Compared with model group

the different doses in Buyang Huanwu Tang group (26

13 g·kg

-1

·d

-1

) increased the neurological function scores 3 to 5 days after treatment

and the basilar artery diameter was significant increased (

0.05). The expression of p-PI3K

p-Akt and eNOS protein was significantly increased (

0.05). The level of NO was significantly increased (

0.05)

and ET-1 was significantly decreased (

0.05). Compared with low-dose group

the neurological scores of high-dose group were significantly increased after 7 days of treatment with Buyang Huanwu Tang (

0.05)

and the diameter of the basilar artery was significantly increased (

0.05)

p-PI3K

The expression of p-Akt and eNOS protein was higher (

0.05)

the increase of NO was more obvious (

0.05)

the decrease of ET-1 was more significant (

0.05).

Conclusion:

The protective effect of Buyang Huanwu Tang on cerebral vasospasm after subarachnoid hemorrhage may be related to up-regulation of p-PI3K

p-Akt and eNOS expression in PI3K/Akt/eNOS signaling pathway

thereby increasing NO production.

关键词

Keywords

references

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