let-7a Inhibits Cell Apoptosis in Hypoxic-Ischemic Neonatal RatBrain Tissue by Inhibiting Fas/FasL
LIU Yifeng, YAN Jun*, ZHOU Ling, LEI Beibei
This study was to explore whether let-7a alleviated the cell apoptosis in hypoxic-ischemic neonatal rat brain tissue by inhibiting Fas/FasL. A hypoxic-ischemic model of neonatal rats was established by ligatingthe carotid artery. Sixty SPF SD neonatal rats were randomly grouped into: sham operation group (Sham group),Model group, let-7a agonist (agomir) group, negative control (NC) agomir group, and let-7a agomir+Fas activatorgroup, 12 animals per group. After modeling, drug injection was performed, and the Sham group and the Modelgroup were injected with the same amount of normal saline. After the administration, the neurological function ofthe rats in each group was evaluated by the NDS (neurological deficit scale). HE staining was used to observe thepathological changes of the brain tissue of the rats in each group. RT-qPCR method was used to determine the expression levels of let-7a, Fas and FasL mRNA in the brain tissue of rats in each group; Western blot was used to determinethe expression of Fas/FasL signaling pathway and apoptosis-related proteins in the brain tissue of rats in each group;TUNEL staining was used to detect the apoptosis rate in the brain tissue of rats in each group; the targeting relationship between let-7a and Fas and FasL was detected by dual-luciferase reporter gene assay. Compared with the Shamgroup, the NSD score, cell apoptosis rate, the mRNA expression level of Fas and FasL, and the protein expressionlevel of Fas, FasL, Bax and Caspase-3 in the Model group were obviously increased (P<0.05); the brain tissue pathological damage was serious. Compared with the Model group, there was no obvious difference in the indicators of therats in the NC agomir group (P>0.05); the NSD score, apoptosis of brain tissue and the expression level of Fas andFasL were obviously decreased in let-7a agomir group (P<0.05), and the pathological damage was alleviated to someextent. Fas activator attenuated the inhibitory effect of overexpression of let-7a on apoptosis of brain tissue in hypoxicischemic neonatal rats (P<0.05). There was a targeting relationship between let-7a and Fas, FasL. let-7a may reducethe cell apoptosis of hypoxic-ischemic neonatal rat brain tissue by inhibiting Fas/FasL.
CN
EN