Department of Neurology, Changle People's Hospital, Changle County, Shandong Province, China.
Eur Rev Med Pharmacol Sci. 2017 Nov;21(22):5275-5282. doi: 10.26355/eurrev_201711_13852.
To investigate the potential effect of 3-n-butylphthalide (NBP) pretreatment on the cerebral ischemia/reperfusion injury in rats and the relevant mechanism.
A total of 90 rats was divided into three groups: Sham operation group (Sham group), ischemia-reperfusion group (I-R group), and NBP pretreatment group (NBP group 75 mg·kg-1·d-1 gavage). Pre-treatment was given once a day within 1 week before establishing the rat model of cerebral ischemia-reperfusion injury. The middle cerebral artery occlusion (MACO) rat models were established with the improved Longa-Zea method on the 7th day after ischemia for 2 h and reperfusion for 24 h in all the rats. We detected the cerebral infarction, the pathologic change of brain, the apoptosis of nerve cell, the production levels of reactive oxygen species (ROS), the content of malonaldehyde (MDA) and the activity of superoxide dismutase (SOD), the water content and the permeability of blood-brain barriers (BBB). In addition, we also observed the expressions of mitogen-activated protein kinase (MAPK, p-38, JNK, ERK1/2) and cleaved caspase-3 in the hippocampus tissues.
Compared with Sham group, we discovered that NBP significantly reduced infarction area, cell apoptosis, BBB damage and water content. Further, we found that NBP could also decrease ROS and MDA, and increase SOD activity in brain tissues of rats with a cerebral ischemia-reperfusion injury. Moreover, results showed that NBP also inhibited the levels p38 and JNK.
NBP protected the cerebral from I/R injury, providing ideas for the expansion of clinical adaptability of NBP and possible approaches for its application.
研究 3-正丁基苯酞（NBP）预处理对大鼠脑缺血再灌注损伤的潜在作用及其相关机制。
将 90 只大鼠分为三组：假手术组（Sham 组）、缺血再灌注组（I-R 组）和 NBP 预处理组（NBP 组，75mg·kg-1·d-1 灌胃）。在建立脑缺血再灌注损伤大鼠模型前 1 周内，每天给予预处理 1 次。所有大鼠在缺血 2 h 后第 7 天采用改良 Longa-Zea 法建立大脑中动脉闭塞（MACO）大鼠模型，并再灌注 24 h。检测脑梗死、脑组织病理改变、神经细胞凋亡、活性氧（ROS）产生水平、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性、脑含水量和血脑屏障（BBB）通透性。此外，还观察了海马组织中丝裂原活化蛋白激酶（MAPK、p38、JNK、ERK1/2）和裂解型半胱氨酸天冬氨酸蛋白酶-3（cleaved caspase-3）的表达。
与 Sham 组相比，NBP 明显减少了脑梗死面积、细胞凋亡、BBB 损伤和脑含水量。此外，NBP 还能降低缺血再灌注损伤大鼠脑组织中 ROS 和 MDA 的含量，增加 SOD 活性。结果还显示，NBP 还抑制了 p38 和 JNK 的水平。
NBP 对脑缺血再灌注损伤具有保护作用，为 NBP 临床适应范围的扩大提供了思路，也为其应用提供了可能的途径。
