Abstract
This study aims to explore the effects of the TLR4 signaling pathway on the apoptosis of neuronal cells in rats with diabetes mellitus complicated with cerebral infarction (DMCI). A DMCI model was established with 40 Sprague Dawley rats, which were assigned into blank, sham, DM + middle cerebral artery occlusion (MCAO) and DM + MCAO + TAK242 groups. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. A TUNEL assay was applied for detecting cell apoptosis, and Western blotting was used for detecting the expression of TLR4, TNF-α, IL-1β and apoptosis-related proteins. Compared with the blank and sham groups, there was an increase in cell apoptosis, expression of Bcl-2, Bax, cleaved caspase-3, TNF-α, IL-1β and TLR4 proteins and MDA content and a decrease in SOD activity in the DM + MCAO and DM + MCAO + TAK242 groups. Compared with those in the DM + MCAO group, rats in the DM + MCAO + TAK242 group exhibited an increase in SOD activity and a decrease in cell apoptosis, expression of Bcl-2, Bax, cleaved caspase-3, TNF-α, IL-1β and TLR4 proteins and MDA content. Inhibition of the TLR4 signaling pathway reduces neuronal cell apoptosis and nerve injury to protect the brain.
Highlights
Resistance, lipid metabolism disorder, endothelial cell dysfunction and blood coagulation, which all affect diabetic vascular disease[13,14]
The fasting blood glucose of rats (n = 30) in the sham, diabetes mellitus (DM) +middle cerebral artery occlusion (MCAO) and DM +MCAO +TAK242 groups was more than 16.7 mmol/L
Toll-like receptor 4 (TLR4), which transmits an inflammatory signal, functions as a portal protein involved in diabetic angiopathies via mediating a signaling pathway that activates the transcription and synthesis of inflammatory factors and has become a new attractive field for studying DM and related complications[13,14]
Summary
Resistance, lipid metabolism disorder, endothelial cell dysfunction and blood coagulation, which all affect diabetic vascular disease[13,14]. There has been no research on the effects of the TLR4 signaling pathway on DMCI. This study aims to explore the effects of the TLR4 signaling pathway on apoptosis of neuronal cells via introducing TAK242 (a TLR4 signaling inhibitor) and establishing a DMCI rat model to provide a theoretical basis for the pathological mechanism for DMCI and the development of a targeted drug treatment
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