ω-3多不饱和脂肪酸对脂多糖诱导的脑损伤新生大鼠的神经保护作用

Neuroprotective effect of ω-3 polyunsaturated fatty acid on brain injury induced by lipopolysaccharide in neonatal rats

目的探讨ω-3多不饱和脂肪酸(ω-3 PUFA)对脂多糖(LPS)诱导的脑损伤新生大鼠的神经保护作用。方法将48只3日龄Sprague-Dawley新生大鼠随机分为对照组、LPS组、ω-3 PUFA组和ω-6 PUFA组,每组12只。LPS组、ω-3 PUFA组和ω-6 PUFA组大鼠腹腔注射0.6 mg·kg^(-1)LPS建立脑损伤模型,然后分别立即腹腔注射等容积的生理盐水、ω-3 PUFA和ω-6 PUFA;对照组大鼠腹腔注射等容积的生理盐水。24 h后处死各组大鼠,取海马组织,采用实时荧光定量聚合酶链反应和Western blot法检测各组大鼠海马组织中Toll样受体4(TLR4)、核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6的mRNA和蛋白表达。结果 LPS组、ω-3 PUFA组、ω-6 PUFA组新生大鼠海马组织中TLR4、NF-κB、TNF-α、IL-1β及IL-6 mRNA和蛋白表达均高于对照组(P<0.05);ω-6 PUFA组新生大鼠海马组织中TLR4、NF-κB、TNF-α、IL-1β及IL-6 mRNA和蛋白表达高于LPS组(P<0.05);ω-3 PUFA组新生大鼠海马组织中TLR4、NF-κB、TNF-α、IL-1β及IL-6 mRNA和蛋白表达均低于LPS组和ω-6 PUFA组(P<0.05)。结论ω-3 PUFA能下调大鼠海马组织中TLR4/NF-κB信号通路,减少炎性因子TNF-α、IL-1β、IL-6释放,对LPS所致的脑损伤新生大鼠有神经保护作用。

Objective To investigate neuroprotective effect of ω-3 polyunsaturated fatty acid（ ω-3 PUFA） on brain injury induced by lipopolysaccharide（ LPS） in neonatal rats. Methods Forty-eight neonatal Sprague-Dawley rats（ 3 days） were randomly divided into control group,LPS group,ω-3 PUFA group and ω-6 PUFA group,with 12 rats in each group. The rats in the LPS group,ω-3 PUFA group and ω-6 PUFA group were given 0. 6 mg·kg-1 LPS via intraperitoneal injection to establish the brain inury model,then equal volume of saline,ω-3 PUFA and ω-6 PUFA was immediately given via intraperitoneal injection respectively; while the rats in the control group were given equal volume of saline. Those rats were sacrificed after 24 hours. The expression of Toll like receptor 4（ TLR4）,nuclear factor-κB（ NF-κB）,tumor necrosis factor-α（ TNF-α）,interleukin（ IL）-1β and IL-6 mRNA in hippocampus was examined by real-time quantitative polymerase chain reaction,meanwhile the expression of TLR4,NF-κB,TNF-α,IL-1β and IL-6 protein in hippocampus was measured by Western blot. Results The expression of TLR4,NF-κB,TNF-α,IL-1β,IL-6 mRNA and protein in rats hippocampus in the LPS group,ω-3 PUFA group andω-6 PUFA group was significantly higher than that in the control group（ P 〈 0. 05）. The expression of TLR4,NF-κB,TNF-α,IL-1β,IL-6 mRNA and protein in rats hippocampus in the ω-6 PUFA group was significantly higher than that in the LPS group（ P 〈 0. 05）. The expression of TLR4,NF-κB,TNF-α,IL-1β,IL-6 mRNA and protein in rats hippocampus in the ω-3 PUFA group was significantly lower than that in the LPS group and ω-6 PUFA group（ P 〈 0. 05）. Conclusion ω-3 PUFA can play a role of neuroprotective effect on brain injury induced by LPS in neonatal rats. The mechanism may involve in down-regulate the activity of TLR4 and NF-κB and reduce the release of TNF-α,IL-1β and IL-6.