Department of Neurosurgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):144-152. doi: 10.26355/eurrev_201908_18641.
To study the effect of 3-n-butylphthalide (NBP) on neuronal apoptosis in rats with cerebral infarction (CI) through the p38/mitogen-activated protein kinase (MAPK) pathway.
A total of 30 rats were divided into control group (healthy rats, n=10), model group (CI rat model, n=10), and NBP group (CI rat model + intraperitoneal injection of NBP, n=10). Then, the neurological function, degree of cerebral ischemia, apoptosis of brain tissues, the protein and messenger ribonucleic acid (mRNA) expressions of p-p38 and MAPK in brain tissues were detected using the neurological score, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and Western blotting, respectively.
In NBP group, the neurological score was significantly lower than in model group, and the difference was statistically significant (p<0.05). The results of TTC staining revealed that the area of the white region in brain slices was significantly larger in model group than in control group, indicating the successful establishment of middle cerebral artery occlusion (MCAO) model. Compared with model group, NBP group had a smaller area and lighter color of the white region in brain slices, suggesting that NBP markedly reduces the MCAO-induced CI. The apoptosis rate in NBP group was higher than in control group (p<0.05), but lower than in model group (p<0.05), while it was higher in model group than in control group (p<0.05). The protein expressions of p38 and MAPK in NBP group were higher than in control group (p<0.05), but lower than in model group (p<0.05), while they were higher in model group than in control group (p<0.05). Moreover, the mRNA expressions of p38 and MAPK were lower in control group than in model group (p<0.05), while they were higher in model group than in NBP group (p<0.05), but there was no significant difference in the mRNA expression of p38 between NBP group and control group (p>0.05).
NBP alleviates neuronal apoptosis in CI by down-regulating the p38 signal and inhibiting the expression of MAPK, thereby treating CI.
通过研究 p38/丝裂原活化蛋白激酶（MAPK）通路，研究 3-正丁基苯酞（NBP）对脑梗死（CI）大鼠神经元凋亡的影响。
将 30 只大鼠分为对照组（健康大鼠，n=10）、模型组（CI 大鼠模型，n=10）和 NBP 组（CI 大鼠模型+腹腔注射 NBP，n=10）。然后，通过神经评分、2,3,5-三苯基四氮唑氯化物（TTC）染色、逆转录-聚合酶链反应（RT-PCR）、末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）检测和 Western 印迹分别检测脑组织中 p-p38 和 MAPK 的蛋白和信使核糖核酸（mRNA）表达、神经功能、脑缺血程度、脑组织凋亡情况。
NBP 组神经评分明显低于模型组，差异有统计学意义（p<0.05）。TTC 染色结果显示，模型组脑切片白色区域面积明显大于对照组，提示大脑中动脉闭塞（MCAO）模型成功建立。与模型组相比，NBP 组脑切片白色区域面积较小，颜色较浅，表明 NBP 可显著减轻 MCAO 诱导的 CI。NBP 组细胞凋亡率高于对照组（p<0.05），但低于模型组（p<0.05），而模型组高于对照组（p<0.05）。NBP 组 p38 和 MAPK 蛋白表达均高于对照组（p<0.05），但低于模型组（p<0.05），而模型组高于对照组（p<0.05）。此外，对照组 p38 和 MAPK 的 mRNA 表达均低于模型组（p<0.05），而模型组高于 NBP 组（p<0.05），但 NBP 组与对照组之间 p38 的 mRNA 表达无显著差异（p>0.05）。
NBP 通过下调 p38 信号和抑制 MAPK 的表达来减轻 CI 中的神经元凋亡，从而治疗 CI。
