姜黄素预处理对大鼠脑缺血/再灌注损伤后AQP-4及脑水肿的影响

Effects of chemical synthesized curcumin preconditioning on the expression of AQP-4 and cerebral edema after focal cerebral ischemia/reperfusion damage in rats

目的研究化学合成的姜黄素预处理对大鼠脑缺血/再灌注损伤后AQP-4及脑水肿的影响。方法采用线栓法阻塞大鼠大脑中动脉(MCAO),建立大鼠局灶性脑缺血/再灌注实验模型,72只SD大鼠被随机分为假手术组(S组)、缺血/再灌注组(I组)和姜黄素(缺血前30 min腹腔给予50、100 mg.kg-1)组(C1和C2组),每组18只。I组和C1、C2组分别在脑缺血/再灌注后24 h处死。观察大鼠神经功能缺失的评分;干湿重法观察大鼠脑含水量的变化,通过收集透出脑血管外的伊文思蓝(EB)来示踪血脑屏障(BBB)的变化,免疫印记法检测AQP-4和c-Jun氨基端激酶(JNK)的表达情况。结果 S组无神经行为改变;C1、C2组脑含水量、EB量、AQP-4表达及JNK磷酸化水平与I组相比明显降低(P<0.05);C1、C2组神经学评分高于Ⅰ组(P<0.05)。结论化学合成的姜黄素可减轻大鼠局灶性脑缺血/再灌注后AQP-4表达水平及BBB的破坏程度,减轻脑水肿,其机制可能与抑制JNK通路的磷酸化激活有关。

Aim To explore the effect of chemical synthesized curcumin（Cur） preconditioning on the expression of aquaporin 4（AQP-4） and cerebral edema after focal cerebral ischemia-reperfusion damage in rats.Methods Local ischemia/reperfusion model of middle cerebral artery occlusion（MCAO） was made by inserting a nylon thread into internal carotid artery in rats.72 healthy SD rats weighing 290~310 g were randomly divided into 3 groups： sham operated group（S）（n=18）,ischemia/reperfusion group（I）（n=18）,Cur group（C1 and C2）（n=18） which were preconditioned with cur 50 or 100 mg·kg-1 intraperitoneally 30 min before focal cerebral ischemia-reperfusion.In I group,NS was given instead of Cur and in S group,the carotid arteries were exposed without performing MCAO.The rats in I group and C1,C2 group were killed 24 hours after cerebral ischemia/reperfusion.Neurological scores were studied,method of dry/wet weight was used to observe water content,and Evans Blue（EB） was collected to observe the changes of blood-brain barrier（BBB） permeability.Expression of AQP-4 and activation of c-Jun N-terminal kinase（JNK） in rat brain were determined by Western blot.Results Sham operated group presented no neurological changes.The water content and EB in C1 and C2 group were significantly lower than those of Ⅰ group（P0.05）.Curcumin could also alleviate the expression of AQP-4 and the phosphorylation of JNK（P0.05）.The neurological deficiency scores in C1 and C2 groups were obviously higher than those of I group（P0.05）.Conclusions Chemical synthesized curcumin can alleviate the expression of AQP-4 and the phosphorylation of JNK,therefore protect the structure of BBB and alleviate the cerebral edema which can exert the neuroprotective effect after focal cerebral ischemia and reperfusion.