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嵌段共聚物纳米胶束包裹的姜黄素通过抑制长链非编码RNA GAS5减轻脑缺血损伤并影响干细胞标志物表达。

Block Copolymer Nanomicelle-Encapsulated Curcumin Attenuates Cerebral Ischemia Injury and Affects Stem Cell Marker Expression by Inhibiting lncRNA GAS5.

作者信息

Li Fengguang, Xu Yan, Wang Xinghua, Cai Xuan, Li Wanli, Cheng Wei, Li Xing, Yan Gangli

机构信息

Department of Neurology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, 430081 Hubei, China.

Department of Pharmacy, General Hospital of Central Theater Command, Wuhan, 430010 Hubei, China.

出版信息

Stem Cells Int. 2023 Feb 17;2023:9821500. doi: 10.1155/2023/9821500. eCollection 2023.

Abstract

Stroke has become the most common cause of death among residents in China, among which ischemic stroke accounts for the vast majority reaching 70% to 80%. It is of great importance to actively investigate the protective mechanism of cerebral ischemia injury after IS (ischemic stroke). We constructed cerebral ischemia injury models MACO rat and (oxygen-glucose deprivation cell model) and set up different interference groups. RT-PCR (reverse transcription PCR) was conducted to detect the expression of lncRNA in neuronal cells, brain tissue, and plasma of different groups, and ELISA (enzyme-linked immunosorbent assay) and western blot were used to detect the expression of the protein in neuronal cells, brain tissue, and plasma of different groups. Cell activity was detected by the CCK-8 assay, while cell apoptosis was examined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. In the rats' neuronal cells and brain tissue, curcumin can inhibit the expression of lncRNA GAS5 (long noncoding RNA growth arrest-specific 5). In oxygen-glucose-deprived neuronal cells , curcumin and low-expressed lncRNA GAS5 can enhance cell activity and decline cell apoptosis, but the addition of curcumin and overexpressed lncRNA GAS5 can make this phenomenon disappear. In neuronal cells, plasma, and brain tissue, curcumin and the low-expressed lncRNA GAS5 can inhibit the expression of IL-1 (interleukin 1 beta), TNF- (tumor necrosis factor alpha), IL-6 (interleukin 6), Sox2 (SRY-box transcription factor 2), Nanog, and Oct4 (octamer-binding transcription factor 4). However, overexpressed lncRNA GAS5 and curcumin made the inhibitory effect disappear. In conclusion, this study demonstrated that curcumin could inhibit the expression of lncRNA GAS5, thereby inhibiting the expression of inflammation-related factors IL-1, TNF-, and IL-6, and ultimately achieve the purpose of attenuating cerebral ischemic cell damage. However, curcumin and lncRNA GAS5 may not alleviate cerebral ischemic cell damage by affecting stem cell differentiation.

摘要

中风已成为中国居民中最常见的死亡原因,其中缺血性中风占绝大多数,达70%至80%。积极研究缺血性中风(IS)后脑缺血损伤的保护机制具有重要意义。我们构建了大脑中动脉闭塞(MACO)大鼠脑缺血损伤模型和氧糖剥夺细胞模型,并设置了不同的干预组。采用逆转录聚合酶链反应(RT-PCR)检测不同组神经元细胞、脑组织和血浆中lncRNA的表达,采用酶联免疫吸附测定(ELISA)和蛋白质免疫印迹法检测不同组神经元细胞、脑组织和血浆中蛋白质的表达。通过细胞计数试剂盒-8(CCK-8)法检测细胞活性,采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测细胞凋亡。在大鼠神经元细胞和脑组织中,姜黄素可抑制长链非编码RNA生长停滞特异性5(lncRNA GAS5)的表达。在氧糖剥夺的神经元细胞中,姜黄素和低表达的lncRNA GAS5可增强细胞活性并减少细胞凋亡,但加入姜黄素和过表达的lncRNA GAS5可使此现象消失。在神经元细胞、血浆和脑组织中,姜黄素和低表达的lncRNA GAS5可抑制白细胞介素1β(IL-1)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、性别决定区Y框蛋白2(Sox2)、Nanog和八聚体结合转录因子4(Oct4)的表达。然而,过表达的lncRNA GAS5和姜黄素使这种抑制作用消失。总之,本研究表明姜黄素可抑制lncRNA GAS5的表达,从而抑制炎症相关因子IL-1、TNF-α和IL-6的表达,最终达到减轻脑缺血细胞损伤的目的。然而,姜黄素和lncRNA GAS5可能不会通过影响干细胞分化来减轻脑缺血细胞损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a57/9957624/781a8bdc5bf3/SCI2023-9821500.001.jpg

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