Mechanism Of Resveratrol In Improving Cerebral Ischemia-Reperfusion Injury In Rats Based On SIRT1/NF-?B Pathway

Objective Through the tail vein inject resveratrol activator of SIRT1 and EX527 inhibitor of SIRT1 and observe the effect of resveratrol on the expression of tumor necrosis factor(TNF)–? and interleukin(IL)-6 and interleukin(IL)-1?,SIRT1 and the nuclear factor-kappa B(NF-?B).Finally,we explored the possible mechanism of resveratrol in improving cerebral ischemia-reperfusion injury in rats and finding a new treatment method for acute cerebral infarction.Methods Rats were selected 7-8 weeks of age,260 ~ 300 g,animal cage,5 per cage,free diet,drinking tap water,standard pellets,room temperature 18 ~ 22 ?,to take natural light,feeding freely,The experiment is carried out in a week.40 healthy male SD rats were randomly divided into sham group,I/R group,Res+I/R group and EX527+I/R group(10 in each group).In addition to the sham group,the cerebral ischemic stroke in the rat model of right middle cerebral artery embolization was constructed,and the improved Longa line embolus method was used in the middle artery infarction model in rats.Res+I/R group(20 mg/kg,in sterile 5% DMSO,100 mg/ml)and EX527 were formulated according to instruction manual(1 ?g/kg,5ug in sterile 5% DMSO in a total volume of 5 ?L,1ug/u L).Res+I/R group was injected with resveratrol via caudal vein at the dose of 20 mg/kg in 15 min before ischemia and 1 min before reperfusion;EX527+I/R group was treated with resveratrol at the same time,and EX527 1?g/kg.The expression levels of interleukin(IL)-1?,IL-6,tumor necrosis factor-?(TNF-?),SIRT1 and NF-?B in peri-ischemic brain tissues were detected using Western blot and RT-PCR respectively in 14 th days.Neurological severity score(NSS)were measured in 1th,3th,7th,14 th days after reperfusion(10 in each group).Results mNSS in Res+ I/R group in 3th,7th,14 th days after reperfusion was significantly lower than those of I/R group and EX527+I/R group(P<0.01);Compared with I/R and EX527+I/R group,the peri-ischemic brain tissue m RNA expression and the protein expression of NF-?B,IL-1?,IL-6 and TNF-? were significantly decreased in Res+I/R group.SIRT1 was significantly increased(P<0.01).Conclusion This study shows that resveratrol can reduce the inflammatory reaction and improve the cerebral ischemia-reperfusion injury in rats by activating SIRT1/NF-?B.