維生素D3於缺血性腦損傷的角色：藉調控糖化終產物受器與第十型類鐸受體訊息以減緩發炎反應之研究

Ischemic stroke accounts for almost 80% of the clinical stroke. Ischemic stroke cause severe brain inflammation, and pro-inflammatory cytokines secretion through the activation of toll-like receptor and inflammasome. Clinical studies indicate that the level of vitamin D concentration is associated with higher risk of stroke. However, the molecular mechanism is remain unclear. This study aimed to investigate the protective action of vitamin D on cerebral ischemia-reperfusion injury and the possible molecular mechanism. Eight-weeks-old male Sprague-Dawley rats were assigned to (1) control group (sham) ; (2) ischemia/reperfusion group (I/R) ; (3) vitamin D deficiency group (VDD group) : dietary deprivation of vitamin D for 14 days ; (4) vitamin D supplements group (VDS group) : 0.7μg /kg vitamin D supplements for 8 days. Middle cerebral artery occlusion (MCAO) was performed with SD rats, and 90 mins late to initiate reperfusion to investigate the effect of vitamin D supplements and deprivation to the brain damage and the performance of relational molecular. Results showed that vitamin D deficiency increased the severity of brain damage, lipid peroxidation products MDA accumulation and pro-inflammatory cytokines release. In contrast, vitamin D supplements improved brain damage. Western blot indicated that vitamin D deficiency may active TLR2-MyD88-NF-κB signaling cascade and NLRP3 inflammasome induce cleaved caspase-1 protein expression, increase IL-1β secretion. However, vitamin D can inhibit TLR2 and NLRP3-related protein expression. Besides, vitamin D can inhibit inflammation through the activation of TLR10-PI3K-AKT signaling pathway.In conclusion, Vitamin D might reduce cerebral ischemic-reperfusion oxidative damage and inflammation by inhibited activation of TLR2, reduced the mature of pro-inflammatory factor IL-1β and activation of TLR10 to protect against cerebral ischemia-reperfusion injury.