脂氧素A4抑制5-LOX合成对脑缺血再灌注损伤具有神经保护作用

Neuroprotective effect of lipoxin A4 on cerebral ischemia-reperfusion injury by inhibiting 5-lipoxygenase synthesis

目的探讨脂氧素A4(LXA4)在大鼠缺血再灌注脑损伤的保护作用中5脂氧合酶(5-LOX)途径的作用和机制。方法 SPF级雄性Wistar大鼠随机分成假手术组、大脑中动脉区局灶性脑缺血(MCAO)组、MCAO+LXA4组及MCAO+LXA4+Boc2组。通过TTC染色法评估脑梗死体积;WB法测定5-LOX、ERK1/2、p-ERK1/2、p38/p-p38、JNK/p-JNK蛋白表达;ELISA法测定5-LOX产物LTB4/LTC4的表达。结果 MCAO+LXA4组动物的神经功能缺损评分、脑含水量、梗死体积百分比较MCAO组明显改善(P<0.05),并被Boc2部分阻断抑制作用;并且MCAO+LXA4组大鼠脑组织中5-LOX、ERK1/2/p-ERK1/2蛋白表达量及其调控产物LTB4/LTC4较MCAO组也明显降低(P<0.05),LXA4的抑制作用被Boc2部分阻断。结论脂氧素A4对大鼠缺血再灌注脑损伤的保护作用与其对5-LOX及其调控产物的抑制作用相关。

Objective The experiment aimed to confirm the neuroprotective effect of lipoxin A4 （LXA4） against cerebral ischemia-reperfusion injury and investigate its potential mechanism of 5-LOX pathway in in rats. Methods SPF male Wistar rats were randomly divided into four groups：Sham-operated group,MCAO group,MCAO＋LXA4 group and MCAO＋LXA4＋Boc2 group.The cerebral infarction volume was assessed by TTC staining.The protein expressions of 5-LOX,ERK1/2,p-ERK1/2,p38/p-p38 and JNK/p-JNK were determined by WB method.The products of 5-LOX-LTB4/LTC4 was measured by Elisa. Results The neurological deficit score,brain water content and infarct volume in MCAO＋LXA4 group were significantly improved compared with MCAO group （ P 〈0.05）,and could partially be blocked by Boc2.In MCAO＋LXA4 group,the expression of 5-LOX,ERK1/2,p-ERK1/2 and their products LTB4/LTC4 were significantly lower compared with MCAO group （ P 〈0.05）.The inhibitory effect of LXA4 was partially blocked by Boc2. Conclusion The protective effect of lipoxin A4 on brain ischemia-reperfusion injury is related to its inhibitory effect on 5-LOX and its regulatory products.