姜黄素对大鼠脑缺血再灌注损伤炎症反应和血脑屏障通透性的作用研究

摘要

目的：探讨姜黄素对大鼠脑缺血再灌注损伤炎症反应和血脑屏障通透性的作用，为姜黄素的应用提供一定的理论依据。方法选取40只雄性SD大鼠，随机分为对照组、模型组、姜黄素低剂量组以及姜黄素高剂量组。除对照组外，其他3组采用线栓法制作大鼠脑缺血再灌注损伤模型。在制作缺血模型前15 min，姜黄素低剂量组给予10 mg／kg姜黄素制剂腹腔注射，姜黄素高剂量组给予50 mg／kg姜黄素制剂腹腔注射，模型组给予相同体积的玉米油腹腔注射。手术后24 h对所有大鼠进行神经功能评分，然后断头取脑组织进行脑组织髓过氧化物酶、基质金属蛋白酶－2（ MMP－2）、MMP－9和伊文思蓝容量水平、肿瘤坏死因子α（ TNF－α）、NF－κB p65水平测定及脑梗死体积的测定。结果模型组、姜黄素低剂量组以及姜黄素高剂量组的脑组织髓过氧化物酶活性、神经功能损伤评分、脑梗死体积、MMP－2、MMP－9、伊文思蓝容量、TNF－α和NF－κB p65均显著高于对照组（ P均＜0．05），而姜黄素低剂量组及姜黄素高剂量组均显著低于模型组（ P均＜0．05），且姜黄素高剂量组优于姜黄素低剂量组（P＜0．05）。结论姜黄素能够明显改善大鼠脑缺血再灌注引起的损伤，其药效机制可能与抑制NF－κB、TNF－α、MMP－2和MMP－9蛋白表达有关系。%Objective It is to analyze and discuss the effect of curcumin on inflammation actions and blood-brain barrier permeability in rats with cerebral ischemia/reperfusion injury, thus to provide a theoretical basis for the applications of this medicine.Methods 40 male SD rats were selected and randomly divided into control group, model group, low and high dosage of curcumin groups.The rats in all the groups except control group were made into ischemia/reperfusion injury models by su-ture method.At 15min before model establishing, low and high dosage of curcumin groups were respectively given 10 mg/kg and 50 mg/kg curcumin by intraperitoneal injection, model group was given the same volume of maize oil by intraperitoneal in-jection.In 24 hours after cerebral ischemia neurological severity scores of all the rats were evaluated, then the heads of the rats were cut off and and brain tissue was gotten to determine the levels of myeloperoxidase,matrix metalloproteinase-2 ( MMP-2), MMP-9 and Evans Blue capacity, TNF-αand NF-κB p65, neurological damage score and infarct volume were evalu-ated too.Results Myeloperoxidase activity, neurological injury score, infarction volume, MMP-2, MMP-9, Evans Blue ca-pacity, TNF-αand NF-κB p65 were significantly higher in model group and curcumin groups than that in control group ( P<0.05), and the indexes above in curcumin groups were significantly lower than that in the model group, and the indexes in high dosage of curcumin group were lower than that in low dosage group ( P<0.05) .Conclusion Curcumin can effectively re-lieve the damage caused by cerebral ischemia and reperfusion in rats, and the pharmacodynamics mechanism may be related with its inhibition of the expression of TNF-αand NF-κB, MMP-2 and MMP-9.