Rana Anil Kumar, Kumar Rajneesh, Shukla Durgesh Nandan, Singh Damanpreet
Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India.
Free Radic Biol Med. 2023 Oct;207:107-119. doi: 10.1016/j.freeradbiomed.2023.07.004. Epub 2023 Jul 4.
Cerebral ischemic stroke is one of the leading causes of adult disability worldwide. Reperfusion is the only therapeutic option with a lot of side effects. In the current study, we investigated the efficacy of rutin and lithium co-treatment in improving post-stroke neurological outcomes in a transient global cerebral ischemia-reperfusion injury rat model. Middle-aged male rats were subjected to transient global cerebral ischemia-reperfusion. NORT and Y-maze were used to assess the cognitive processes. Lipid peroxidation, protein carbonylation, and nitric oxide assays were performed to study oxidative stress. The excitotoxicity index was calculated by HPLC. Real time-PCR and western blotting were performed to study gene and protein expressions. The co-administration of rutin and lithium improved the overall survival, recognition memory, spatial working memory, and neurological score following cerebral ischemia-reperfusion in rats. Further, a marked decrease in malonaldehyde, protein carbonyls, and nitric oxide levels was observed following combined treatment. The mRNA expression of antioxidant (Hmox1 and Nqo1) and pro-inflammatory (Il2, Il6, and Il1β) markers were significantly attenuated in the rutin and lithium co-administrated group. The treatment inhibited the Gsk-3β and maintained a normal pool of the downstream β-catenin and Nrf2 proteins. The results revealed that co-administration of rutin and lithium had a neuroprotective potential, suggesting it to be a viable treatment to overcome post-stroke deaths and neurological complications.
脑缺血性中风是全球成年人残疾的主要原因之一。再灌注是唯一的治疗选择，但有很多副作用。在本研究中，我们在短暂性全脑缺血再灌注损伤大鼠模型中研究了芦丁和锂联合治疗对改善中风后神经功能结局的疗效。对中年雄性大鼠进行短暂性全脑缺血再灌注。使用旷场试验和Y迷宫评估认知过程。进行脂质过氧化、蛋白质羰基化和一氧化氮检测以研究氧化应激。通过高效液相色谱法计算兴奋性毒性指数。进行实时聚合酶链反应和蛋白质印迹法以研究基因和蛋白质表达。芦丁和锂联合给药改善了大鼠脑缺血再灌注后的总体存活率、识别记忆、空间工作记忆和神经评分。此外，联合治疗后观察到丙二醛、蛋白质羰基和一氧化氮水平显著降低。在芦丁和锂联合给药组中，抗氧化剂（血红素加氧酶1和醌氧化还原酶1）和促炎（白细胞介素2、白细胞介素6和白细胞介素1β）标志物的信使核糖核酸表达明显减弱。该治疗抑制糖原合成酶激酶-3β并维持下游β-连环蛋白和核因子E2相关因子2蛋白的正常水平。结果表明，芦丁和锂联合给药具有神经保护潜力，表明它是克服中风后死亡和神经并发症的一种可行治疗方法。
