ω-3多不饱和脂肪酸对脂多糖所致脑损伤新生大鼠海马组织中氧化应激产物和细胞凋亡的影响

Effect of ω-3 polyunsaturated fatty acid on oxidative stress production and apoptosis in hippocampus of neonatal rats with brain injury induced by lipopolysaccharide

目的探讨ω-3多不饱和脂肪酸(PUFA)对脂多糖(LPS)所致脑损伤新生大鼠海马组织中氧化应激产物和细胞凋亡的影响。方法将48只3日龄新生Sprague Dawley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组新生大鼠腹腔注射0.6 mg·kg-1LPS后分别立即腹腔注射等容积生理盐水、ω-3 PUFA和ω-6 PUFA;对照组大鼠腹腔注射等容积生理盐水;24 h后快速断头取海马组织,检测各组新生大鼠海马组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)、氧化型GSH(GSSG)水平,并计算GSSG/GSH比值;原位末端转移酶标记法检测各组新生大鼠海马组织细胞凋亡指数(AI)。结果与对照组比较,LPS组、ω-6 PUFA组和ω-3 PUFA组新生大鼠海马组织中SOD和GSH水平显著降低(P<0.05),MDA、GSSG水平及GSSG/GSH比值显著升高(P<0.05)。与LPS组比较,ω-6 PUFA组新生大鼠海马组织中SOD和GSH水平显著降低(P<0.05),MDA、GSSG水平及GSSG/GSH比值显著升高(P<0.05);ω-3 PUFA组新生大鼠海马组织中SOD和GSH水平显著升高(P<0.05),MDA、GSSG水平及GSSG/GSH比值显著降低(P<0.05)。与ω-6 PUFA组比较,ω-3 PUFA组新生大鼠海马组织中SOD和GSH水平显著升高(P<0.05),MDA、GSSG水平及GSSG/GSH比值显著降低(P<0.05)。LPS组、ω-6 PUFA组和ω-3 PUFA组新生大鼠海马组织AI显著高于对照组(P<0.05);ω-6 PUFA组新生大鼠海马组织AI显著高于LPS组(P<0.05);ω-3 PUFA组新生大鼠海马组织AI显著低于ω-6 PUFA组和LPS组(P<0.05)。结论ω-3 PUFA能够减轻LPS所致脑损伤新生大鼠海马组织中的氧化应激反应,减少海马组织细胞凋亡,对LPS所致的脑损伤具有保护作用。

Objective To investigate the effects of ω-3 polyunsaturated fatty acid（PUFA） on oxidative stress production and apoptosis in hippocampus of neonatal rats with brain injury induced by lipopolysaccharide（LPS）. Methods Fortyeight 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 given0. 6 mg·kg-1 LPS via intraperitoneal injection,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 all given equal volume of saline. The rats in each group were sacrificed at 24 hours after intraperitoneal injection with saline or fat emulsions to obtain the hippocampus. The levels of superoxide dismutase（SOD） and malondialdehyde（MDA）,reduced glutathion（GSH）,oxidized glutathione（GSSG）were detected and GSSG/GSH was calculated. The apoptotic index was measured by terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling. Results Compared with the control group,the levels of SOD and GSH in hippocampus of rats in the LPS group,ω-6 PUFA group and ω-3 PUFA group were significantly decreased（P〈0. 05）,and the levels of MDA,GSSG and the ratio of GSSG/GSH were significantly increased（P〈0. 05）. Compared with the LPS group,the levels of SOD and GSH in hippocampus of rats in ω-6 PUFA group were significantly decreased（P〈0. 05）,the levels of MDA,GSSG and the ratio of GSSG/GSH were significantly increased（P〈0. 05）; the levels of SOD and GSH in hippocampus of rats in ω-3 PUFA group were significantly increased（P〈0. 05）,the levels of MDA,GSSG and the ratio of GSSG/GSH were significantly decreased（P〈0. 05）. Compared with the ω-6 PUFA group,the levels of SOD and GSH in hippocampus of rats in ω-3 PUFA group were significantly decreased（P〈0. 05）,the levels of MDA,GSSG and the ratio of GSSG/GSH were significantly increased（P〈0. 05）. The apoptotic index in the LPS group,ω-6 PUFA group and ω-3 PUFA group was higher than that in the control group（P〈0. 05）. The apoptotic index in the ω-6 PUFA group was higher than that in the LPS group（P〈0. 05）. The apoptotic index in the ω-3 PUFA group was lower than that in the LPS group and ω-6 PUFA group（P〈0. 05）. Conclusionω-3 PUFA can alleviate the oxidative stress,and decrease the apoptosis of hippocampus in neonatal rats with brain injury induced by LPS. So it has a neuroprotective effect in brain injury induced by LPS.