Abstract：
Intracerebral hemorrhagic (ICH) stroke is a major cause of death and disability globally, with no proper treatment available so far. Rutin, a dietary flavonoid, has shown protection against cerebral ischemic stroke due to its antioxidant and anti-inflammatory attributes. However, the efficacy of rutin against ICH stroke remained unexplored. Therefore, in the current study, we investigated the effect of rutin in an ICH stroke zebrafish larva model. The larvae were exposed to atorvastatin (1.25 μM) in system water for induction of experimental ICH. Rutin treatment reduced the hematoma size, ROS production and decreased apoptosis in the zebrafish larvae brains. Reduction in the malondialdehyde and protein carbonyl level in the rutin-treated larvae also indicated quenching of the free radicals. The treatment increased the expression of tight junction claud5a gene and decreased the mRNA level of matrix metalloproteases (mmp2 and mmp9). Furthermore, rutin treatment also attenuated the genomic expression of oxidative markers (nrf2, hmox1a, sod1, and gpx) and inflammatory genes (il6, tnfa, il10, and irf2a) related to ICH. The Gsk-3β activity was also downregulated, and a normal pool of β-catenin and Nrf2 was maintained in the larvae treated with rutin. The current study suggested that rutin protects ICH stroke via suppressing oxidative stress and inflammatory events in a zebrafish model.
摘要：
脑出血（ICH）中风是全球范围内死亡和残疾的主要原因，到目前为止还没有适当的治疗方法。芦丁,一种膳食类黄酮，由于其抗氧化和抗炎特性，已显示出对缺血性脑卒中的保护作用。然而,芦丁对ICH卒中的疗效尚待研究.因此,在目前的研究中，我们研究了芦丁在ICH中风斑马鱼幼虫模型中的作用。将幼虫暴露于在系统水中的阿托伐他汀(1.25μM)以诱导实验性ICH。芦丁治疗减少了血肿大小，斑马鱼幼虫大脑中ROS的产生和细胞凋亡的减少。芦丁处理的幼虫中丙二醛和蛋白质羰基水平的降低也表明自由基的猝灭。该处理增加了紧密连接claud5a基因的表达，并降低了基质金属蛋白酶（mmp2和mmp9）的mRNA水平。此外，芦丁治疗也减弱了氧化标记的基因组表达(nrf2，hmox1a，sod1和gpx)和炎症基因(il6，tnfa，il10和irf2a)与ICH相关。Gsk-3β活性也下调，在用芦丁处理的幼虫中保持了正常的β-catenin和Nrf2库。目前的研究表明，在斑马鱼模型中，芦丁通过抑制氧化应激和炎症事件来保护ICH卒中。
