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Iranian Journal of Basic Medical Sciences، جلد ۲۷، شماره ۶، صفحات ۷۴۰-۷۴۶
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عنوان انگلیسی Febuxostat attenuates secondary brain injury caused by cerebral hemorrhage through inhibiting inflammatory pathways
چکیده انگلیسی مقاله Objective(s): Neuroinflammation is considered an important step in the progression of secondary brain injury (SBI) induced by cerebral hemorrhage (ICH). The nucleotide-binding and oligomerization structural domain-like receptor family of pyridine structural domain-containing 3 (NLRP3) inflammasomes play an important role in the immune pathophysiology of SBI. Febuxostat (Feb) is a xanthine oxidase inhibitor that is approved for the treatment of gout and has been found to have potent anti-inflammatory effects. However, it has been less studied after ICH and we aimed to explore its protective role in ICH.Materials and Methods: We established an autologous blood-brain hemorrhage model in C57BL/6 mice. Functions of co-expressed genes were analyzed by trend analysis and bioinformatics analysis. Enzyme-linked immunosorbent assay were used to assess the inflammatory factor levels. Fluoro-Jade B histochemistry and TUNEL staining were used to detect neuronal apoptosis. Immunofluorescence staining and western blotting were used to detect the expression of NLRP3 inflammasomes.Results: Pretreatment with Feb reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders in vivo. Feb was found to modulate inflammation-related pathways by trend analysis and bioinformatics analysis. In addition, Feb inhibited microglia activation and elevated cytokine levels after ICH. Furthermore, double immunofluorescence staining showed that co-localization of NLRP3 with Iba1 positive cells was reduced after treatment with Feb. Finally, we found that Feb inhibited the activation of the NLRP3/ASC/caspase-1 pathway after ICH. Conclusion: By inhibiting the NLRP3 inflammasome, preconditioning Feb attenuates inflammatory injury after ICH. Our findings may provide new insights into the role of Feb in neuroprotection.
کلیدواژه‌های انگلیسی مقاله Bioinformatics analysis, Febuxostat, Inflammation, Intracerebral hemorrhage NLRP3 inflammasome, Second brain injury, Trend analysis
نویسندگان مقاله | yang bai
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Hongxia Shi
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Ying Zhang
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Chenyu Zhang
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China|West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China


| Bin Wu
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Xinghan Wu
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Zhenwei Fang
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Qi Wang
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Xiutian Sima
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China


| Tiejun Zhang
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
نشانی اینترنتی https://ijbms.mums.ac.ir/article_23946.html
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