Rh-relaxin-2 attenuates oxidative stress and neuronal apoptosis via ERK-nNOS-NO pathway after germinal matrix hemorrhage in rats

作者：Jun Liu, Yonghua Cai, Khalil Ur Rahman, Qixiong Zhou, Guangjie Liu, Huibin Kang, Mingzhou Li, Shichao Zhang, Gang Wang, Wenfeng Feng, Xian Zhang, Guozhong Zhang, Ye Song, Li Peng · 发表于：Fluids and Barriers of the CNS · 年份：2025 · DOI：10.1186/s12987-024-00616-7 · 被引用次数：5 · 研究领域：Pregnancy-related medical research

Oxidative stress and neuronal apoptosis could be an important factor leading to post-hemorrhagic consequences after germinal matrix hemorrhage (GMH). Previously study have indicated that relaxin 2 receptor activation initiates anti-oxidative stress and anti-apoptosis in ischemia-reperfusion injury. However, whether relaxin 2 activation can attenuate oxidative stress and neuronal apoptosis after GMH remains unknown. To investigate the beneficial effect of relaxin 2 on oxidative stress injury and neuronal apoptosis by GMH, a total of 150 rat pups were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Recombinant human relaxin-2 (rh-relaxin-2) was administered intraperitoneally injections at 1 h and 13 h after GMH. Lenti-virus with sgRXFP1 and sgCtrl was administered intracerebroventricular (i.c.v.) on the left side of the brain to inhibit the RXFP1 at 2d prior to GMH induction, and LY321499, ERK inhibitor, was administered by i.c.v. injection at 1 h on the left side of the brain prior to GMH induction, respectively. Co-immunoprecipitation, immunofluorescence, TUNEL, Fluoro-Jade C, DHE staining, western blot, Nitrix Oxide (NO) quantification and side effect experiments were performed to evaluate post-GMH. We found endogenous relaxin-2 interacts with RXFP1 and both protein colocalized in neurons on the first day after GMH. Additionally, RXFP1 activation with rh-relaxin-2 significantly inhibited oxidative stress and neuronal apoptosis in GMH + rh-relaxin-...