莱菔硫烷对大鼠局灶性脑缺血再灌注损伤炎症反应的影响

Effects of sulforaphane on inflammation of focal cerebral ischemia/reperfusion injury in rats

摘要:

目的：研究莱菔硫烷（sulforaphane，ＳＦＮ）对大鼠局灶性脑缺血再灌注损伤炎症反应的影响，并进一步探讨其可能的机制。方法：利用线栓法制备大鼠大脑中动脉栓塞（middle cerebral artery occlusion，MCAO）模型，于MCAO后1 h腹腔注射ＳＦＮ 5 mg/kg。缺血2 h，再灌注24 h时，检测大鼠神经功能缺损评分并用TTC染色测定脑梗死体积；通过检测脑组织髓过氧物酶的含量反映中性粒细胞浸润和炎症反应的程度；Western blot检测核因子－κB（nuclear factor-κB，NF-κB）、肿瘤坏死因子－α（tumor necrosis factor-α，TNF-α）以及白介素－６（interleukin-6，IL-6）的表达变化。结果：与模型组相比，5 mg/kg ＳＦＮ治疗组均能改善大鼠缺血再灌注损伤后神经功能缺损[（2.49±0.48）分 vs. （1.34±0.62）分，P=0.000] 、减少脑梗死体积[（0.41±0.02）% vs. （0.26±0.03）%，P=0.000]，降低髓过氧化物酶（myeloperoxidase，MPO）的含量[（0.43±0.02） Ｕ/g vs. （0.35±0.02） U/g，P=0.000]。Western blot的结果显示，ＳＦＮ组脑组织NF-κB、TNF-α以及IL-6蛋白表达与MCAO组比较表达明显降低，分别为（0.39±0.05） vs. （1.65±0.05），P=0.000；（0.30±0.05） vs. （0.91±0.03），P=0.000；（0.49±0.11） vs. （1.50±0.03），P=0.000。结论：ＳＦＮ可以通过减轻炎症反应对大鼠脑缺血/再灌注损伤起神经保护作用，其相关机制可能与其降低 NF-κB、TNF-α以及 IL-6表达有关。

Abstract:

Objective：To explore the protective effects of sulforaphane（ＳＦＮ） on inflammation of focal cerebral ischemia/reperfusion in－jury in rats and its possible mechanism． Methods：Middle cerebral artery occlusion（MCAO） was induced by intraluminal suture． Five mg/kg ＳＦＮ was administrated intraperitoneally at 60 min after MCAO. At 24 h after reperfusion，neurologic deficiency scores were de－tected and the infarct volume was evaluated by TTC staining． Myeloperoxidase（MPO） activities in rat brain were measured as an in－dex of neutrophil infiltration. Expressions of nuclear factor-κB（NF-κB），tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in rat brain were determined by Western blot. Results：Neurological deficiency scores（（2.49±0.48） vs. （1.34±0.62），P=0.000） were significantly improved，infarcted volume was diminished（（0.41±0.02）% vs. （0.26±0.03）%，P=0.000） and activity of MPO in cere－bral tissues（（0.43±0.02） U/g vs. （0.35±0.02） U/g，P=0.000） was decreased in 5 mg/kg ＳＦＮ group than in MCAO group. Results of Western blot showed that SFN could also decrease the expression of NF-κB，TNF-α and IL-6 compared with those in MCAO group（（0.39±0.05） vs. （1.65±0.05），P=0.000；（0.30±0.05） vs. （0.91±0.03），P=0.000；（0.49±0.11） vs. （1.50±0.03），P=0.000）. Conclusions：ＳＦＮ exerts the neuroprotective effect on cerebral ischemia/reperfusion injury in rats through inhibiting the inflammatory response，which may be associated with the inhibition of NF-κB，TNF-α and IL-6 expression.