Knockdown of IL-6 Plays a Crucial Role in Protection of Hypoxia-Ischemia in Neonatal Rats via Inhibiting Casp3 and BAX Signaling Pathway

Abstract Background: The effect of interleukin-6 (IL-6) knockdown on hypoxia-ischemia (HI) of neonatal rat models was investigated to explore the underlying molecular regulation mechanism. Methods: To establish the HI model, we treated 7days postnatal Sprague-Dawley (SD) rats with the right carotid artery ligation and had them exposed to the environment of 8% oxygen and 92% nitrogen for 2 h, respectively. Then, the neurologic function and morphology changes were assessed. Subsequently, IL-6 siRNA lentivirus was injected into cerebral cortex motor area 2 days before HI; meanwhile, the interference efficiency was detected by quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot. Immunofluorescence staining of Glial fibrillary acidic protein (GFAP), Hexaribonucleotide Binding Protein-3 (NeuN) and IL-6 were used to identify the location and interference effect of IL-6. In order to further research the underlying mechanisms, the expressions of downstream molecular including Bcl-2-associated X protein (BAX) and Casp3 were examined following IL-6 up-regulation by QRT-PCR. Results: It was found that both the growth of cortical neurons and the length of axon were promoted after IL-6 interference, and the cell apoptosis was decreased. In addition, the expression of BAX and Casp3 were closely associated with IL-6. Conclusions: The present findings confirmed that the decreased IL-6 improves the deficiencies in neurologic function and morphology induced by HI, and the potential mechanism may be closely related with the regulation of Casp3 and BAX.