丙泊酚对大鼠缺血-再灌注脑TNF-α、IL-10、NF-κB的影响

摘要

目的 研究丙泊酚对缺血性脑炎性因子表达的影响.方法 SD大鼠30只随机分为假手术对照(S)组、脑缺血-再灌注(IR)组(双侧颈总动脉夹闭造成暂时性脑缺血)、丙泊酚预处理(PP)组(缺血前60 min输注丙泊酚50 mg·kg-1·h-1),丙泊酚后处理(PA)组(再灌注后10 min给予丙泊酚50 mg·kg-1·h-1)以及不行脑缺血丙泊酚(P)组(输注丙泊酚50 mg·kg-1·h-1),每组6只.用酶联免疫吸附法(ELISA)测定脑组织肿瘤坏死因子α(TNF-α)和白细胞介素-10(IL-10),用同位素([32P]-ATP)方法测定脑内核因子-κB(NF-κB)的变化.结果 与S组比较,IR组TNF-α明显增高[(2.57±0.19)Pg/g vs.(1.60±0.15)pg/g](P<0.05),同时IL-10明显增高[(11.59±1.32)pg/gvs.(7.97±1.96)pg/g](P<0.05).与IR组比较,PP组TNF-α明显减低[(1.88±0.26)pg/g vs.(2.57±0.19)pg/g](P<0.05),IL-10水平明显降低[(8.35±1.00)pg/g vs.(11.59±1.32)Pg/g](P<0.05),NF-κB活性明显减低.PA组TNF-α、IL-10、NF-κB与IR组差异无统计学意义.IL-10和NF-κB水平与TNF-α活性呈现平行变化关系.结论 脑缺血前丙泊酚预处理可抑制脑的炎性介质TNF-α、IL-10和NF-κB的增高,但脑缺血-再灌注后应用丙泊酚对缺血性炎性介质的增高没有抑制作用;丙泊酚对缺血性炎性介质TNF-α的作用可能与抑制NF-κB转导途径有关.%Objective To study the effects of propofol on the expressions of tumor necrosis factor(TNF)-α, interleukin-10 (IL-10) and nuclear factor-κB(NF-κB) in rat cerebrum undergoing ischemia and reperfusion. Methods Thirty rats were randomly divided into five groups with 6 rats each. The rats in group S accepted sharm operation as the controls, in group IR focal cerebral ischemia Concentrations of TNF-α and IL-10 in the cerebrum were measured by enzyme-linked immunosorbance assay(ELISA). An isotope([32P]-ATP) technique was applied for detecting nuclear factor-κB(NF-κB) in rat cerebral cortex. Electrophoretic mobility shift assay (EMSA) was performed in nuclear extracts from cerebral tissues. Results Compared with group S,TNF-α of group IR increased [(2.57±0.19) pg/g vs. (1.60±0.15) pg/g](P<0.05),so did the IL-10 [(11.59±1.32) pg/g vs. (7.97±1.96) pg/g](P<0.05). Compaered with group IR,TNF-α of group PP decreased [(1.88±0.26) pg/g vs. (2. 57±0. 9) pg/g](P<0.05) ,so did the IL-10 [(8.35±1.00) pg/g vs. (11.59±1.32) pg/g](P< 0.05),with decreased activity of NF-κB. There was no significant difference in the levels of TNF-α, IL-10 and NF-κB between group IR and group PA. The changes of IL-10 and NF-κB activity were parallel to that of TNF-α. Conclusion Pre-treatment with propofol can prevent the elevation of inflammatory factors in the cerebrum undergoing ischemia and reperfusion, which was not when used after cerebral ischemia. The effect of propofol on reduction of TNF-α production in ischemic cerebrum may be through inhibiting transduction pathway of NF-κB.