ω-3多不饱和脂肪酸对脂多糖所致新生大鼠脑损伤Toll-NF-κB信号通路调节作用

Effect of ω-3 PUFAs on regulation of Toll-like receptor 4 and nuclear factor-ΚB signaling pathway in neonatal rats with brain injury induced by LPS

目的探讨ω-3PUFAs在脂多糖(LPS)诱导的新生大鼠脑损伤中对TLR4、NF-κB信号通路的调节作用。方法将96只SD新生大鼠按随机数字法分为对照组,ω-3组,ω-6组和LPS组。4组大鼠分别采用生理盐水或LPS腹腔注射后,立即注射生理盐水或不同的脂肪乳剂,使用时间分别为1天或5天,建立感染所致新生大鼠脑损伤模型;1天或5天后处死新生大鼠,检测TLR4mRNA、NF-κB mRNA和对应蛋白水平的变化。结果 LPS注射后的第1天、第5天,新生大鼠TLR4mRNA、NF-κB mRNA表达及其对应的蛋白水平均明显高于对照组(P均<0.05)。1d时ω-3组TLR4mRNA、NF-κB mRNA表达及其对应的蛋白水平均低于ω-6组和LPS组(P均<0.05)。5d时ω-3组TLR4mRNA、NF-κB mRNA表达及其对应的蛋白水平均低于ω-6组和LPS组(P均<0.05)。不论第1d和第5d,ω-3PUFAs均可明显降低TLR4mRNA、NF-κB mRNA表达及其对应的蛋白水平(P均<0.05);而ω-6PUFAs能提高TLR4mRNA、NF-κB mRNA表达及对应的蛋白水平(P均<0.05)。结论ω-3PUFAs能下调TLR4、NF-κB活性,在LPS所致的脑损伤中具有抗炎作用。

Objective To investigate the effects of ω-3 PUFAs on regulation of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） signaling pathway in neonatal rats with brain injury induced by LPS. Methods Totally 96 neonatal Sprague-Dawley rats were divided into control group,ω-3 group,ω-6 group,and LPS group.Intraperitoneal injection with saline or LPS was administered and immediately saline or fat emulsions was injected to establish a model of rat with brain injury induced by infection and the duration time was 1 day or 5 days respectively.Those groups were sacrificed at 1d or 5 d after intraperitoneal injection with saline or fat emulsions.Expression levels of TLR4 mRNA and NF-κB mRNA were examined by real-time PCR,meanwhile the levels of TLR4,and NF-κB in the hippocampus were measured by Western Blot. Results The expressions of TLR mRNA and NF-κB mRNA and the protein level of TLR4 and NF-κB in the hippocampus were significantly different in four groups（all P〈0.05）.TLR mRNA and NF-κB mRNA and the protein expression levels in ω-3 group were lower than those in ω-6 group and LPS group on 1 d after injection （all P〈0.05）.And the protein expression levels of TLR mRNA and NF-κB mRNA in ω-3 group were lower than those in ω-6 group and LPS group on five days after injection （all P〈0.05）.No matter the first day or the fifth day,the expression of TLR mRNA and NF-κB mRNA and the level of TLR4 and NF-κB in ω-3 group were significantly lower than those in ω-6 group（all P〈0.05）. Conclusion ω-3 PUFAs can down regulate the activity of signaling pathway of TLR4 and NF-κB,so it may has an anti-inflammatory effect on brain injuryinduced by LPS.