Abstract: Objective To explore the protective effect of resveratrol on aluminum induced cranial nerve injury in rats based on the nod-like receptor family pyrin domain containing 3（NLRP3）- nuclear factor kappa-beta（NF-κB）- metalloproteinase 9（MMP-9） pathway. Methods Totally 40 adult rats were divided into a normal control group,an aluminum exposure group,and resveratrol low-dose and high-dose groups（100 and 200 mg/kg）. Rats in the aluminum exposure group and the low-dose and high-dose resveratrol group were exposed to aluminum trichloride to establish a model of cranial nerve function injury. During the exposure period,the rats in the low-dose and high-dose resveratrol groups were given daily resveratrol gavage intervention,while the normal control group and the aluminum exposure group were given an equal volume of normal saline. After the experiment,neurological function indicators,blood-brain barrier leakage level,neuronal apoptosis levels in brain tissue,brain tissue NLRP3,NF-κB,MMP-9 mRNA protein expression levels,tumor necrosis factor-α（TNF-α）,interleukin-1 beta（IL-1β）,nitric oxide synthase（iNOS） levels. Results Compared with the normal control group,the aluminum exposure group showed an increase in neurobehavioral scores,swimming distance,escape latency,blood-brain barrier leakage rate,apoptosis index of cranial nerve cells,NLRP3,NF-κB,and MMP-9 mRNA protein levels in cranial tissue（0.86 ±0.09 vs 3.58±0.29,0.75± 0.08 vs 4.20±0.22,0.97± 0.06 vs 4.12±0.18, 0.29± 0.05 vs 1.74± 0.19,0.38±0.07 vs 1.86± 0.18,0.34±0.08 vs 1.79±0.20）, as well as an increase in levels of inflammatory factors TNF-α, IL-1β, and iNOS in cranial tissue,and a decrease in the number of crossing the original platform position,and the differences were statistically significant（all P<0.05）. Compared with the aluminum exposure group,resveratrol low-dose and high-dose groups neurobehavioral scores,swimming distance,escape latency,blood-brain barrier leakage rate,apoptosis index of cranial nerve cells,cranial tissue NLRP3,NF-κB,MMP-9 mRNA protein levels（3.58±0.29 vs 2.68±0.19,1.62±0.13,4.20±0.22 vs 2.55±0.17,1.72±0.17,4.12±0.18 vs 3.14±0.13,2.01±0.10;1.74±0.19 vs 1.04±0.13,0.73±0.10,1.86±0.18 vs 1.53±0.16,1.02±0.10,1.79±0.20 vs 1.27±0.18,0.74±0.11）,cranial tissue inflammatory factor TNF-α,IL-1β,and iNOS levels decreased,and the number of crossing the original platform position increased,the differences were statistically significant（allP <0.05）. Compared with the resveratrol low-dose group, the resveratrol high-dose group showed a decrease in neurobehavioral scores,swimming distance,escape latency,blood-brain barrier leakage rate,apoptosis index of cranial nerve cells,cranial tissue NLRP3,NF-κB,MMP-9 mRNA protein levels and cranial tissue inflammatory factors TNF-α,IL-1β,iNOS levels,an increase in the number of crossing the original platform position,and the differences were statistically significant（all P<0.05）. Conclusion Resveratrol has a significant therapeutic effect on aluminum exposure induced cranial nerve injury in rats,and its mechanism is related to the inhibition of NLRP3,NF-κB,and MMP-9 mRNA protein expression induced by aluminum exposure,thereby inhibiting the activation of the NLRP3-NF-κB-MMP-9 pathway.

Key words: NLRP3, NF-κB, MMP-9, Resveratrol, Aluminum, Cranial nerve injury