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冰片开放血脑屏障的作用及机制

The Role and Mechanism of Borneol to Open the Blood-Brain Barrier.

作者信息

Wu Tao, Zhang Aiqin, Lu Hongyang, Cheng Qiaoyuan

机构信息

1 Nantong Rich Hospital, Nantong, Jiangsu Province, People's Republic of China.

2 Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, People's Republic of China.

出版信息

Integr Cancer Ther. 2018 Sep;17(3):806-812. doi: 10.1177/1534735418767553. Epub 2018 Apr 13.

Abstract

BACKGROUND

The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors.

OBJECTIVE

The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms.

MATERIALS AND METHODS

Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy.

RESULTS

The concentration of Evans blue in the borneol group was higher than in the control group ( P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group ( P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group ( P < .05).

CONCLUSION

Borneol can open the BBB, which might be related with the increased expression of ICAM-1.

摘要

背景

血脑屏障(BBB)是颅内恶性肿瘤治疗中最大的挑战。

目的

本研究旨在确定冰片在打开血脑屏障中的作用并阐明其潜在机制。

材料与方法

将20只Sprague-Dawley(SD)大鼠随机分为冰片组,经胃内给予10%冰片玉米油(2 mL/kg)和对照组。30分钟后,注射2%伊文思蓝(4 mL/kg)。30分钟后,使用伊文思蓝标准曲线分析脑组织。另外40只SD大鼠随机分为高、中、低剂量冰片组和对照组。实验组中的每只大鼠经胃内分别给予10%冰片玉米油(分别为2 mL/kg、1.25 mL/kg和0.5 mL/kg)。对照组注射1.25 mL/kg玉米油。30分钟后,处死大鼠并收集脑组织。通过免疫组织化学检测闭合蛋白、闭合蛋白-1、一氧化氮合酶、P-糖蛋白和细胞间细胞黏附分子-1(ICAM-1)的表达。

结果

冰片组伊文思蓝浓度高于对照组(P <.05)。实验组ICAM-1表达的平均密度高于对照组(P <.05)。相比之下,仅高剂量组与对照组之间ICAM-1的阳性面积和总密度存在显著差异(P <.05)。

结论

冰片可打开血脑屏障,这可能与ICAM-1表达增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d1/6142104/3bb304c43919/10.1177_1534735418767553-fig1.jpg

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