Mazhar Maryam, Yang Guoqiang, Xu Houping, Liu Yulin, Liang Pan, Yang Luyin, Spáčil Roman, Shen Hongping, Zhang Dechou, Ren Wei, Yang Sijin
National Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
Institute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, China.
Front Pharmacol. 2023 Jun 7;14:1197433. doi: 10.3389/fphar.2023.1197433. eCollection 2023.
One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but the scientific basis for its mechanism is lacking. To investigate the neuroprotective role of ZLHXTY capsules for ICH-induced oxidative injury through the regulation of redox imbalance with the Nrf2 signaling pathway. Autologous blood injection model of ICH in C57BL/6J mice was employed. Three treatment groups received ZLHXTY once daily through oral gavage at doses 0.35 g/kg, 0.7 g/kg, and 1.4 g/kg, started after 2 h and continued for 72 h of ICH induction. The neurological outcome was measured using a balance beam test. Serum was tested for inflammatory markers IL-1β, IL-6, and TNF-α through ELISA, oxidative stress through hydrogen peroxide content assay, and antioxidant status by total antioxidant capacity (T-AOC) assay. Nuclear extract from brain tissue was assayed for Nrf2 transcriptional factor activity. RT-qPCR was performed for Nfe2l2, Sod1, Hmox1, Nqo1, and Mgst1; and Western blotting for determination of protein expression of Nrf2, p62, Pp62, Keap, HO1, and NQO1. Fluoro-jade C staining was also used to examine neuronal damage. ZLHXTY capsule treatment following ICH demonstrated a protective effect against oxidative brain injury. Neurological scoring showed improvement in behavioral outcomes. ELISA-based identification demonstrated a significant decline in the expression of serum inflammatory markers. Hydrogen peroxide content in serum was found to be reduced. The total antioxidant capacity was also reduced in serum, but the ZLHXTY extract showed a concentration-dependent increase in T-AOC speculating at its intrinsic antioxidant potential. Nrf2 transcriptional factor activity, mRNA and protein expression analyses revealed normalization of Nrf2 and its downstream targets, which were previously elevated as a result of oxidative stress induced by ICH. Neuronal damage was also reduced markedly after ZLHXTY treatment as revealed by Fluoro-jade C staining. ZLHXTY capsules possess an intrinsic antioxidant potential that can modulate the ICH-induced redox imbalance in the brain as revealed by the normalization of Nrf2 and its downstream antioxidant targets.
脑出血（ICH）是出血性中风中严重致残和致命的亚型之一，目前缺乏有效的治疗方法。自上世纪以来，在中国的一些省份，（ZLHXTY）胶囊已被有效用于治疗脑出血，但缺乏其作用机制的科学依据。本研究旨在通过Nrf2信号通路调节氧化还原失衡，探讨ZLHXTY胶囊对脑出血诱导的氧化损伤的神经保护作用。采用C57BL/6J小鼠自体血注射脑出血模型。三个治疗组在脑出血诱导后2小时开始，每天一次通过口服灌胃给予ZLHXTY，剂量分别为0.35 g/kg、0.7 g/kg和1.4 g/kg，持续72小时。使用平衡木试验测量神经功能结局。通过ELISA检测血清中的炎症标志物IL-1β、IL-6和TNF-α，通过过氧化氢含量测定检测氧化应激，通过总抗氧化能力（T-AOC）测定检测抗氧化状态。检测脑组织核提取物中Nrf2转录因子活性。对Nfe2l2、Sod1、Hmox1、Nqo1和Mgst1进行RT-qPCR检测；采用蛋白质印迹法测定Nrf2、p62、Pp62、Keap、HO1和NQO1的蛋白表达。还用荧光玉C染色检测神经元损伤。脑出血后ZLHXTY胶囊治疗对脑氧化损伤具有保护作用。神经评分显示行为结局有所改善。基于ELISA的鉴定表明血清炎症标志物的表达显著下降。发现血清中过氧化氢含量降低。血清中的总抗氧化能力也降低，但ZLHXTY提取物显示T-AOC呈浓度依赖性增加，推测其具有内在的抗氧化潜力。Nrf2转录因子活性、mRNA和蛋白表达分析表明Nrf2及其下游靶点恢复正常，这些靶点先前因脑出血诱导的氧化应激而升高。荧光玉C染色显示，ZLHXTY治疗后神经元损伤也明显减少。ZLHXTY胶囊具有内在的抗氧化潜力，通过Nrf2及其下游抗氧化靶点的正常化，可调节脑出血诱导的大脑氧化还原失衡。
Zotero 插件
