Influence and Mechanism of Naoqing Penbi Weiru on the Permeability of Blood-brain Barrier in Rats after Acute Ischemic Stroke

SHI He-yuan; SONG Wan-shan; HUANG Yan

doi:10.11653/syfj2013200166

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Influence and Mechanism of Naoqing Penbi Weiru on the Permeability of Blood-brain Barrier in Rats after Acute Ischemic Stroke

更新时间：2024-01-04

- Influence and Mechanism of Naoqing Penbi Weiru on the Permeability of Blood-brain Barrier in Rats after Acute Ischemic Stroke
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 19, Issue 20, Pages: 166-171(2013)
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- DOI：10.11653/syfj2013200166
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- Published：2013
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SHI He-yuan, SONG Wan-shan, HUANG Yan. Influence and Mechanism of Naoqing Penbi Weiru on the Permeability of Blood-brain Barrier in Rats after Acute Ischemic Stroke[J]. Chinese journal of experimental traditional medical formulae, 2013, 19(20): 166-171.
DOI：

SHI He-yuan, SONG Wan-shan, HUANG Yan. Influence and Mechanism of Naoqing Penbi Weiru on the Permeability of Blood-brain Barrier in Rats after Acute Ischemic Stroke[J]. Chinese journal of experimental traditional medical formulae, 2013, 19(20): 166-171. DOI： 10.11653/syfj2013200166.

摘要

目的: 观察脑清喷鼻微乳对急性脑梗死大鼠血脑屏障(blood-brain barrier

BBB)超通透性影响及其相关分子机制。方法: 采用自身栓子法制备大鼠大脑中动脉栓塞模型(MCAO)

筛选后随机分为对照组、模型组、脑清喷鼻微乳组

并给予药物干预。脑清喷鼻微乳组予脑清喷鼻微乳0.19 mL·kg-1(相当于含麝香酮0.011 mg·kg-1)滴鼻给药

每日3次

对照组与模型组给予相同时间点等量生理盐水滴鼻。每组于1

7 d 3个时相对大鼠进行神经功能缺损评分后

取材观察各时相大鼠大脑皮质缺血区神经元及内皮细胞形态

检测伊文思蓝(EB)、紧密连接蛋白-1(zonula occludins protins-1

ZO-1)、层黏连蛋白(laminin

LN)及水通道蛋白-4(aquaporin protein-4

AQP-4)含量。结果: 与同一时相正常组相比

模型组Bederson's评分、EB及AQP-4蛋白含量明显升高(P<0.05)

ZO-1、Laminin蛋白含量显著降低(P<0.05)

神经元坏死较多及内皮细胞损害严重。与同一时相模型组相比

脑清喷鼻微乳组Bederson's评分、EB及AQP-4蛋白含量明显降低(P<0.05)

ZO-1

Laminin蛋白含量显著升高(P<0.05)

神经元存活率较高及内皮细胞损害较轻。同组内不同时相相比较

脑清喷鼻微乳组Bederson's评分、EB及AQP-4蛋白含量逐渐降低(P<0.05)

ZO-1蛋白含量逐渐升高(P<0.05)

Laminin蛋白含量3 d后逐渐升高(P<0.05)

1 d时神经元及内皮细胞水肿最严重

7 d时神经元变性坏死最多

内皮细胞基膜及细胞器缺损最为严重。结论: 脑清喷鼻微乳通过调控血脑屏障(BBB)3层结构中的主要蛋白ZO-1

Laminin及AQP-4蛋白的含量

调节BBB通透性

保护BBB结构及功能的完整性

减少神经元凋亡

减轻可逆性神经元损伤

促进神经功能的恢复。

Abstract

Objective: To observe the effects of Naoqing Penbi Weiru on the permeability of blood-brain barrier(BBB) and ultrastructure of cortex endothelial cells after acute ischemic stroke. Method: The model of middle cerebral artery occlusion (MCAO) was established using self-embolus method. After screening

the male SD rats were randomly divided into the control group

the model group

the Naoqing Penbi Weiru group and gived drug intervention. Naoqing Penbi Weiru group nasal drip with Naoqing Penbi Weiru 0.19 mL·kg-1(amount to contain muscone 0.011 mg·kg-1)

three times one day. Control group and model group nasal drip with equivalent normal saline at the same time. Every group detected the permeability of nerve function by the Bederson's score

the permeability of blood-brain barrier(BBB) by the Evans blue dye (EB dye)

watch the ultrastructure of Cortex endothelial cells in ischemic region by electron microscopy

Zonula occludins protins-1(ZO-1)

laminin(LN) and Aquaporin Protein-4(AQP-4)by western-blot. Result: Compared with the same phase control group

in the model group

the Bederson's score

the EB dye and the protein of AQP-4 significantly improved(P<0.05). The protein of ZO-1 and LN were significantly lower(P<0.05). Neurons and endothelial cell morphology were worse than the control group.Compared with the same phase model group

in the Naoqing Penbi Weiru group

the Bederson's score

the EB dye and the protein of AQP-4 significantly decreased(P<0.05). The protein of ZO-1 and LN were significantly higher(P<0.05). Neurons and endothelial cell morphology were better than the modol group. With the same group but at different time points compared

in the Naoqing Penbi Weiru group

Bederson's score

the Evans Blue dye (EB dye) and the protein of AQP-4 gradually decreased(P<0.05)

the protein of ZO-1 were gradually higher(P<0.05) and the protein of Laminin were gradually higher(P<0.05)at 3 day. Neurons and endothelial edema were the most serious at 1 day. At 7 day

degeneration and necrosis of neurons was the most and basement membrane and organelle of endothelial cell defects most serious. Conclusion: Naoqing Penbi Weiru group can adjust BBB permeability

protect the integrity of BBB structure and function

reduce the apoptosis of neurons

reduce the damage of reversible neurons and promote the recovery of neurological function by regulating and controling the main protein AQP-4

LN and ZO-1 in the three layer structure of BBB.

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Related Institution

Affiliated Hospital of Nanjing University of Chinese Medicine，Jiangsu Province Hospital of Chinese Medicine

The Affiliated Hospital of Nanjing University of Chinese Medicine/ Jiangsu Province Hospital of Chinese Medicine

Institute of Information on Traditional Chinese Medicine，China Academy of Chinese Medical Sciences

School of Chinese Materia Medica， Beijing University of Chinese Medicine

Xiyuan Hospital， China Academy of Chinese Medical Sciences

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