摘要
目的 探讨伏立诺他(SAHA)调节高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)信号通路对脑出血(ICH)小鼠神经功能损伤的影响。方法 通过注射Ⅶ型胶原酶建立ICH小鼠模型。将造模小鼠随机分为ICH组、SAHA组(15 mg/kg SAHA)、重组高迁移率组蛋白B1(rHMGB1)组(16μg/kg rHMGB1)、SAHA+rHMGB1组(16μg/kg rHMGB1+15 mg/kg SAHA),每组10只;以不注射Ⅶ型胶原酶的10只小鼠为假手术组。干预结束后,对小鼠进行神经功能缺损评分(NDS),检测小鼠认知障碍状况及脑水肿变化、血清TNF-α及IL-1β水平、神经元细胞凋亡数量、血肿周围组织中HMGB1/TLR4通路相关蛋白的表达。结果 与ICH组比较,假手术组、SAHA组NDS评分、脑水肿率、神经元凋亡数量、TNF-α水平、IL-1β水平及HMGB1、TLR4蛋白表达显著降低,分辨指数显著升高(均P<0.05),rHMGB1组NDS评分、脑水肿率、神经元凋亡数量、TNF-α水平、IL-1β水平及HMGB1、TLR4蛋白表达显著升高,分辨指数显著降低(均P<0.05)。与SAHA+rHMGB1组比较,SAHA组NDS评分、脑水肿率、神经元凋亡数量、TNF-α水平、IL-1β水平及HMGB1、TLR4蛋白表达显著降低,分辨指数显著升高(均P<0.05),rHMGB1组NDS评分、脑水肿率、神经元凋亡数量、TNF-α水平、IL-1β水平及HMGB1、TLR4蛋白表达显著升高,分辨指数显著降低(均P<0.05)。结论 SAHA抑制HMGB1/TLR4信号通路的炎症反应,改善ICH小鼠神经功能。
Objective To investigate the impact of vorinostat(SAHA)on neurological damage in mice with intracerebral hemorrhage(ICH)by regulating the high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway.Methods The ICH mouse model was established by injecting typeⅦcollagenase.The model mice were randomly grouped into ICH group,SAHA group(15 mg/kg SAHA),recombinant high mobility histone B1(rHMGB1)group(16μg/kg rHMGB1)and SAHA+rHMGB1 group(16μg/kg rHMGB1+15 mg/kg SAHA),with 10 mice in each group.Ten mice without injection of typeⅦcollagenase were used as the sham operation group.After the intervention,the neurological deficit score(NDS)was performed on the mice.The cognitive impairment and brain edema changes,serum TNF-αand IL-1βlevels,the number of neuronal apoptosis,and the expression of HMGB1/TLR4 pathway-related proteins in tissues surrounding the hematoma were detected.Results Compared with those in ICH group,NDS score,cerebral edema rate,the number of neuronal apoptosis,TNF-αlevel,IL-1βlevel and HMGB1 and TLR4 protein expression in sham operation group and SAHA group were significantly decreased,and the resolution index was significantly increased(all P<0.05);NDS score,cerebral edema rate,number of neuronal apoptosis,TNF-αlevel,IL-1βlevel and HMGB1 and TLR4 protein expression in rHMGB1 group were significantly increased,and resolution index was significantly decreased(all P<0.05).Compared with those in SAHA+rHMGB1 group,NDS score,cerebral edema rate,number of neuronal apoptosis,TNF-αlevel,IL-1βlevel and HMGB1 and TLR4 protein expression in SAHA group were significantly decreased,and resolution index was significantly increased(all P<0.05);NDS score,cerebral edema rate,number of neuronal apoptosis,TNF-αlevel,IL-1βlevel and HMGB1 and TLR4 protein expression in r HMGB1 group were significantly increased,and resolution index was significantly decreased(all P<0.05).Conclusion SAHA inhibits the inflammatory response of HMGB1/TLR4 signaling pathway and improves neural function in ICH mice.
作者
李阳阳
方建
王晓雪
LI Yangyang;FANG Jian;WANG Xiaoxue(Department of Neurology for the Elderly,the First Affiliated Hospital of Henan University,Kaifeng 475001,China)
出处
《临床神经病学杂志》
CAS
2024年第4期292-296,共5页
Journal of Clinical Neurology
基金
2021年度河南省医学科技攻关计划项目(LHGJ20210555)。
