巨噬细胞移动抑制因子抑制剂对蛛网膜下腔出血大鼠脑损伤的保护作用

Protective effects of macrophage migration inhibitory factor inhibitor on brain injury in rats with subarachnoid hemorrhage

目的探讨巨噬细胞移动抑制因子(MIF)抑制剂对蛛网膜下腔出血(SAH)大鼠脑损伤的保护作用。方法将120只12月龄健康雄性大鼠按照随机数字表法分为假手术组、SAH组、小剂量、中剂量和大剂量抑制剂组,每组24只。采用枕大池二次注血法制作大鼠SAH动物模型,小剂量、中剂量和大剂量抑制剂组分别给予10 mg/kg、20 mg/kg和40 mg/kg剂量MIF抑制剂注射大鼠腹腔,测定五组大鼠炎症因子、神经细胞凋亡、脑含水量、血脑屏障通透性和神经功能情况。结果大鼠脑组织白介素-1β、肿瘤坏死因子-α及白介素-6蛋白表达、神经细胞凋亡指数、脑水肿指数、伊文氏蓝含量及神经行为学评分五组间比较,差异均有统计学意义(F=76.406、62.664、64.106、40.211、24.869、60.229、43.664,均P<0.01),与假手术组比较,SAH组白介素-1β、肿瘤坏死因子-α及白介素-6蛋白表达、神经细胞凋亡指数、脑水肿指数和伊文氏蓝含量增高,神经行为学评分下降,差异均有统计学意义(P<0.01),MIF抑制剂腹腔注射可逆转上述作用,且呈剂量-疗效依赖关系(P<0.05)。结论MIF抑制剂对SAH大鼠脑损伤具有明显的保护作用,且呈量效关系。

Objective To investigate the protective effects of macrophage migration inhibitory factor(MIF)inhibitor on brain injury in rats with subarachnoid hemorrhage(SAH).Methods A total of 12012-month-old healthy male rats were randomly divided into Sham surgery group,SAH group,lowdose,medium-dose and high-dose inhibitor groups according to the random number table method,with 24 rats in each group.The SAH rat animal models were created via double autologous blood injection into the cisterna magna.Rats in the low-dose,medium-dose and high-dose inhibitor groups were injected intraperitoneally with MIF inhibitor at dosages of 10 mg/kg,20 mg/kg and 40 mg/kg,respectively.Inflammatory factors,neuronal cell apoptosis,brain water content,blood-brain barrier permeability and neurologic function were determined in the five groups of rats.Results The expressions of interleukin-1β,tumor necrosis factor-α,and interleukin-6 in the brain tissues of rats,percentage of apoptotic neuronal cells,brain edema index,Evans blue content,and neurobehavioral scores of rats were compared among the five groups,and showed statistically significant differences(F=76.406,62.664,64.106,40.211,24.869,60.229,43.664;all P<0.01).Compared with the Sham surgery group,the expressions of interleukin-1β,tumor necrosis factor-α,and interleukin-6,percentage of apoptotic neuronal cells,brain edema index,and Evans blue content in the SAH group were significantly elevated,while the neurobehavioral scores were substantially decreased(P<0.01).Intraperitoneal injection of MIF inhibitor significantly reversed the aforementioned effects and demonstrated a dose-dependent relationship(all P<0.05).Conclusion The MIF inhibitor displays an obvious protective effect on brain injury in SAH rats and exhibits a dose-response relationship.