姜黄素对缺血性脑室周围白质软化新生大鼠的脑保护作用

Cerebralprotective effect of curcumin on neonatal rats with ischemic periventricular leukomalacia

目的体内评估姜黄素对缺血性脑室周围白质软化(PVL)新生大鼠的脑保护作用。方法通过双侧颈总动脉结扎制备2日龄缺血型PVL新生大鼠动物模型。将新生大鼠分为假手术组(sham组)、缺氧缺血组(HI组)、缺氧缺血前用药组(HI前用药组)和缺氧缺血后用药组(HI后用药组)。在双侧颈总动脉结扎前和后应用姜黄素50 mg/(kg.d),制模后48 h取材,分别观察脑病理组织学变化,检测氧化/抗氧化物质,检测Bcl-2、Bax以及剪切型Caspases-3、9蛋白表达。结果脑病理显示两个用药组的脑白质病变较HI组明显改善,其中重度白质病变的发生率分别较HI组降低了62.5%和43.8%,另有12.5%的脑白质完全正常;免疫组化显示用药组脑内的O4阳性少突胶质细胞(OL)前体和髓鞘碱性蛋白(MBP)阳性成熟OL的积分光密度(IOD)值均较缺氧缺血组显著增高;姜黄素明显抑制由缺氧缺血引起的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和过氧化物酶(CAT)活性的下降、谷胱甘肽(GSH)含量减少,以及丙二醛(MDA)含量升高;用药组的Bcl-2合成量亦较HI组明显增加,Bax以及Caspases-3、9活化片段的合成量均较HI组明显减少。结论姜黄素对缺氧缺血引起的脑白质损伤具有良好的保护作用,与其调节脑内的抗氧化系统、以及调节脑内的凋亡相关蛋白的表达有关。

Objective To evaluate the cerebralprotective effect of curcumin on neonatal rats with ischemic periventricular leukomalacia（PVL）in vitro.Methods The models of ischemic two-day-old neonatal rats were established by ligating bilateral common carotid arteries.The neonatal rats were divided into the sham group,hypoxic-ischemic（HI）group,pre-treat with curcumin before HI group and post-treat with curcumin after HI group.The neonatal rats were given curcumin at a dose of 50 mg/kg·d before or after ligating bilateral common carotid arteries.The assessment of cerebral pathology,the detection of the oxidation/anti-oxidation materials,and the analysis of the expression of Bcl-2/Bax and cleaved-Caspases-3、9 were undertaken in 48 hours after the surgery.Results The patho-logical changes in cerebral white matter were improved significantly in both of the curcumin groups compared to those in the HI group with 62.5% and 43.8% of severe pathological changes and 12.5% of normal white matters,respectively.The IOD（integrated optical density）values of O4（oligodendrocyte marker O4）and MBP（myelin basic protein） staining were increased,the activities of SOD（superoxide dismutases）,GPx（glutathione peroxidase）and CAT（catalase）and level of GSH（glutathione）were increased,the level of MDA（malondialdehyde）was decreased,the expression of Bcl-2 was increased,the expression of Bax and the activation of caspase-3,9 were decreased significantly in both of curcumin groups compared to those in the HI group,respectively.Conclusions Curcumin exerts well protection on ischemia-induced white matter injury,and the effect may be related with its regulation on anti-oxidative defense system and the expression of apoptosis-associated proteins.