Shi Yafeng, Zhu Gemin, Yan Jun, Zhang Linxin, Du Yongku, Bian Zhuoqiong, Fan Jing
Department of Neurology, Xi'an Fifth Hospital, Xi'an, 710082, Shaanxi Province, China.
Department of Neurology, Xi'an Central Hospital, Xi'an, 710000, Shaanxi Province, China.
Cell Biochem Biophys. 2025 Mar 22. doi: 10.1007/s12013-025-01702-9.
This study explored the neuroprotective mechanism of rosuvastatin calcium (RSC) combined with hyperbaric oxygen (HBO) in rats with leukoaraiosis (LA), and its impact on the p38MAPK signaling pathway (SPW). Clean-grade male SD rats were used as subjects, which were assigned into Sham group (SG), LA group (LAG), RSC group (RSCG), HBO group (HBOG), and RSC + HBO group (combination group, CG), 20 rats in each. At 14 d post-modeling, the effects of RSC, HBO, and RSC + HBO treatment on the cognitive function, brain neuronal cell apoptosis, brain tissue matrix metalloproteinases (MMPs) family gene expression, and the status of the p38MAPK SPW in LA rats were analyzed. As against the LAG, the escape latency (EL) was shortened, the count of platform crossings was augmented, the number of brain neuronal cell apoptosis decreased, the relative expression (RE) of brain TIMP-1, MMP-2, MMP-3, and MMP-9 mRNA were reduced (P < 0.05), and the RE of brain cleaved caspase (Cas)-3 and p-p38MAPK proteins were reduced in the RSCG, HBOG, and CG (P < 0.05); As against the RSCG and HBOG, the CG showed more visible improvements in all indicators (P < 0.05). The combination of RSC and HBO can inhibit brain neuronal cell apoptosis and the expression of the MMPs family genes in rats with LA by suppressing the overactivation of the p38MAPK SPW, which is beneficial for the recovery of the rats' cognitive function.
本研究探讨了瑞舒伐他汀钙（RSC）联合高压氧（HBO）对脑白质疏松症（LA）大鼠的神经保护机制及其对p38丝裂原活化蛋白激酶信号通路（SPW）的影响。选用清洁级雄性SD大鼠作为研究对象，将其分为假手术组（SG）、LA组（LAG）、RSC组（RSCG）、HBO组（HBOG）和RSC+HBO组（联合组，CG），每组20只。造模后14天，分析RSC、HBO及RSC+HBO治疗对LA大鼠认知功能、脑神经元细胞凋亡、脑组织基质金属蛋白酶（MMPs）家族基因表达及p38MAPK SPW状态的影响。与LAG组相比，RSCG组、HBOG组和CG组的逃避潜伏期（EL）缩短，平台穿越次数增加，脑神经元细胞凋亡数量减少，脑TIMP-1、MMP-2、MMP-3和MMP-9 mRNA的相对表达（RE）降低（P<0.05），脑裂解型半胱天冬酶（Cas）-3和p-p38MAPK蛋白的RE降低（P<0.05）；与RSCG组和HBOG组相比，CG组在所有指标上的改善更明显（P<0.05）。RSC与HBO联合应用可通过抑制p38MAPK SPW的过度激活，抑制LA大鼠脑神经元细胞凋亡及MMPs家族基因的表达，有利于大鼠认知功能的恢复。
