Huang Jun-Yao, Ma Qiang, Qi Ya-Jie, Wang Zhi-Yao, Liu Xiao-Guang, Zhu Yi-Ming, Li Yu-Ping
Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225000, Jiangsu, China.
Neuromolecular Med. 2025 Feb 20;27(1):15. doi: 10.1007/s12017-025-08838-0.
This in vivo study explored the impact of TUBB6 inhibition in intracerebral hemorrhage (ICH), focusing on its effects on hematoma volume, microtubule stability, inflammation, neuronal preservation, and sensorimotor recovery. Sprague-Dawley rats was used to induce ICH by collagenase injection into the right striatum, followed by administration of TUBB6 antisense oligonucleotide (ASO) or Control ASO directly into the hematoma site 3 h post-ICH. Outcomes measured included hematoma volume, microtubule stability (acetylated α-tubulin), levels of inflammatory cytokines, mitogen-activated protein kinase (MAPK) pathway activity, neuronal degeneration (Fluoro-Jade C staining), and cell integrity (Cresyl Violet staining). Functional recovery was assessed using neurological severity scores (mNSS), corner turn, forelimb-placing, and rotarod tests, with body weight tracked for up to 28 days. TUBB6 expression increased with the severity of hemorrhage in the ICH models. TUBB6 ASO significantly reduced hematoma volume at 24- and 72-h post-ICH, restored acetylated α-tubulin levels, suppressed MAPK signaling pathway, and decreased pro-inflammatory markers with increased IL-10. TUBB6 ASO also reduced neuronal degeneration and improved cell viability. In terms of functional outcomes, the TUBB6 ASO + ICH group exhibited reduced mNSS scores, improved body weight maintenance, and better performance on corner turn, forelimb-placing and rotarod tests compared to the Control ASO + ICH group. TUBB6 ASO treatment demonstrated therapeutic potential in a rat model of ICH by reducing hematoma volume, stabilizing microtubules, modulating the MAPK signaling pathway, and mitigating inflammation. It also preserved neuronal integrity and enhanced sensorimotor recovery, suggesting its effectiveness as a therapeutic approach to improve ICH outcomes.
这项体内研究探讨了TUBB6抑制在脑出血（ICH）中的作用，重点关注其对血肿体积、微管稳定性、炎症、神经元保护和感觉运动恢复的影响。采用Sprague-Dawley大鼠，通过向右侧纹状体注射胶原酶诱导脑出血，然后在脑出血后3小时将TUBB6反义寡核苷酸（ASO）或对照ASO直接注入血肿部位。测量的结果包括血肿体积、微管稳定性（乙酰化α-微管蛋白）、炎性细胞因子水平、丝裂原活化蛋白激酶（MAPK）信号通路活性、神经元变性（Fluoro-Jade C染色）和细胞完整性（甲酚紫染色）。使用神经严重程度评分（mNSS）、转角、前肢放置和转棒试验评估功能恢复情况，并跟踪体重长达28天。在ICH模型中，TUBB6表达随出血严重程度增加而升高。TUBB6 ASO在脑出血后24小时和72小时显著减小血肿体积，恢复乙酰化α-微管蛋白水平，抑制MAPK信号通路，并降低促炎标志物水平，同时增加白细胞介素-10。TUBB6 ASO还减少了神经元变性并改善了细胞活力。在功能结果方面，与对照ASO + ICH组相比，TUBB6 ASO + ICH组的mNSS评分降低，体重维持改善，在转角、前肢放置和转棒试验中的表现更好。TUBB6 ASO治疗通过减小血肿体积、稳定微管、调节MAPK信号通路和减轻炎症，在大鼠ICH模型中显示出治疗潜力。它还保留了神经元完整性并增强了感觉运动恢复，表明其作为改善ICH预后的治疗方法的有效性。
