Study on the relationship between Toll like receptor 4 expression and apoptosis in periventricular leukomalacia rat model induced by hypoxia-ischemia

Abstract

Objective To investigate the correlation between Toll like receptor 4 (TLR4) expression and apoptosis in periventricular leukomalacia (PVL) rat model induced by hypoxia-ischemia. Methods One hundred and forty three-day-old sprague-dawley (SD) rats, which were divided into experimental group (ischemia-hypo-xia group) and control group (sham operation group) randomly, were used to establish a hypoxic model by ligating the right common carotid artery and inhaling gas mixtures with 60 mL/L oxygen and 940 mL/L nitrogen.The rats were killed 6 h, 12 h, 24 h, 3 d, 7 d after model reproducing and the brain tissues were used for the following experiments.The pathological changes and apoptosis of brain tissues were detected by way of hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel) assay respectively, and TLR4 expression was detected by adopting immunohistochemistry and reverse-transcription polymerase chain reaction(RT-PCR). The data were analyzed by using the SPSS 19.0 software. Results TLR4 expression in the modeling rat brain commenced to increase in 6 hours (0.541±0.069, 0.166±0.058)and reached the peak in 3 days(1.932±0.161, 0.300±0.039), and then began to decline in 7 days (1.242±0.109, 0.220±0.025) post hypoxia-ischemia.Compared with the control group, there were statistical significances at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The apoptosis of brain ti-ssue cells in the modeling rat brain started to increase at 6 hours(21.33±3.50) and reached the peak in 3 days (35.97±4.20), and then began to decline in 7 days (31.02±4.22) post hypoxia-ischemia.Compared with the control group, there were statistical significance at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The TLR4 expression was positively correlated with cell apoptosis (r=0.774, 0.575, all P<0.05). Conclusions In the rat model of PVL induced by hypoxia-ischemia, TLR4 is likely to injure the neural cell through apoptosis. Key words: Periventricular leukomalacia; Toll like receptor 4; Apoptosis; Hypoxia-ischemia