■缺血性中风是一种严重的疾病,发病率很高,致残率和死亡率。缺血性卒中涉及多种发病机制,如炎症和神经元细胞凋亡。激活的信号转导和转录激活因子1的蛋白质抑制剂(PIAS1)在各种生物过程中起着至关重要的作用,包括炎症。PIAS1在缺血再灌注损伤中也下调并参与疾病过程。然而,PIAS1在脑缺血中的作用尚不清楚.
■Sprague-Dawley(SD)大鼠大脑中动脉阻塞(MCAO)。通过Longa试验探讨PIAS1在缺血性脑梗死中的作用及机制,氯化2,3,5-三苯基四唑(TTC)染色,Morris水迷宫(MWM)试验,苏木精-伊红(HE)染色,脑含水量的量化,逆转录-定量聚合酶链反应(RT-qPCR),酶联免疫吸附测定(ELISA),末端脱氧核苷酸转移酶脱氧尿苷三磷酸(dUTP)缺口末端标记(TUNEL),蛋白质印迹和免疫荧光测定。
■与假手术大鼠相比,PIAS1在MCAO诱导大鼠中的表达下降。PIAS1的过表达降低了Longa神经评分,梗死面积的百分比,病理异常,游泳的逃避潜伏期和大脑含水量的百分比,并增加了MCAO诱导的大鼠的平台穿越次数和目标象限的时间。此外,PIAS1的过表达降低了MCAO诱导的IL-1β的含量,IL-6和TNF-α,但进一步升高血清和脑组织中IL-10的浓度。此外,PIAS1的过表达逆转了MCAO诱导的细胞凋亡率和Bax的相对蛋白水平,裂开的caspase3和Bcl-2。PIAS1的过表达也逆转了参与NF-κB途径的蛋白质水平。
■PIAS1减少炎症和细胞凋亡,从而通过调节NF-κB通路减轻MCAO诱导的大鼠缺血性脑梗死。
UNASSIGNED: Ischemic stroke is a severe disorder with high incidence, disability rate and mortality. Multiple pathogenesis mechanisms are involved in ischemic stroke, such as inflammation and neuronal cell apoptosis. Protein inhibitor of activated signal transducer and activators of transcription 1 (
PIAS1) plays a crucial role in various biological processes, including inflammation.
PIAS1 is also downregulated in ischemia-reperfusion injury and involved in the disease processes. However, the role of
PIAS1 in cerebral ischemia is unclear.
UNASSIGNED: Sprague-Dawley (SD) rats were induced with middle cerebral artery occlusion (MCAO). The role and mechanisms of PIAS1 in ischemic cerebral infarction were explored by Longa test, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Morris water maze (MWM) test, hematoxylin-eosin (HE) staining, quantification of brain water content, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), Western blot and immunofluorescence assays.
UNASSIGNED: The expression of
PIAS1 in MCAO-induced rat was declined compared to sham rats. Overexpression of PIAS1 reduced the Longa neurological scores, the percent of infarction area, the pathological abnormality, the escape latency of swimming and the percent of brain water content, and increased the number of platform crossings and time in the target quadrant in the MCAO-induced rats. Besides, overexpression of PIAS1 decreased the MCAO-induced the contents of IL-1β, IL-6 and TNF-α, but further elevated the concentrations of IL-10 in both sera and brain tissues. Moreover, overexpression of PIAS1 reversed the MCAO-induced apoptosis rate and the relative protein level of Bax, cleaved caspase3 and Bcl-2. Overexpression of
PIAS1 also reversed the level of proteins involved in NF-κB pathway.
UNASSIGNED: PIAS1 reduced inflammation and apoptosis, thereby alleviating ischemic cerebral infarction in MCAO-induced rats through regulation NF-κB pathway.