依达拉奉对重症急性胰腺炎大鼠脑损伤保护作用的试验研究

An experimental study on protective effects of edaravone on cerebral damage caused by severe acute pancreatitis in rats

目的:研究依达拉奉对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)相关性脑损伤的保护作用。方法:72只健康雄性SD大鼠随机分SAP组、处理组及正常对照组,每组24只。采用胰管穿刺注射5%牛磺胆酸钠制备大鼠SAP模型,处理组加用依达拉奉。分别在术后第3 h、6 h、12 h采集血液、胰腺组织、脑组织标本,观察血浆淀粉酶、胰腺组织病理变化,应用ELISA法检测血浆、脑组织TNFα-的水平,测定脑组织含水量、丙二醛含量及微血管内聚集和附壁的白细胞计数。应用RT-PCR法检测脑组织核因子-κB p65 mR-NA的表达情况。结果:SAP组6 h、12 h脑组织含水量比正常对照组明显升高(P<0.05);而处理组6 h、12 h上述指标比SAP组显著下降(P<0.05)。SAP组各时间点的胰腺组织病理学评分分值,脑组织NFκ-B p65 mRNA表达水平、TNFα-水平,脑组织丙二醛含量及微血管内白细胞聚集和附壁计数,血浆淀粉酶、TNFα-水平,与正常对照组比较均明显增高(P<0.05);处理组6 h、12 h上述各项指标比SAP组明显降低(P<0.05)。结论:依达拉奉可能通过清除SAP大鼠脑自由基,抑制核因子-κB的激活,减少TNFα-等细胞因子的生成,抑制炎症反应,从而对SAP大鼠脑损伤起保护作用。

Objective： To study the protective effects of edaravone on cerebral damage caused by severe acute pancreatitis（SAP） in rats. Methods： A total of 72 male healthy SD rats were randomly divided into SAP group （24 rats）, treated group （24 rats） and normal control group （24 rats）. Rat SAP model was induced by pricking injection of 5% sodium taurocholate into the pancreatic duct. The treated group was treated by edaravone. A series of blood, pancreatic tissue and brain tissue samples were obtained at 3, 6 and 12 hours after operation respectively. Hemodiastase and histopathological change of pancreas were observed. The levels of TNF-α in the blood and brain tissue were measured with ELISA. Water content, MDA content, the count of leucocytes accumulation and adhesion of the brain tissue were measured. Levels of NF-κB p65 mRNA in rat brain tissue were measured by RT-PCR. Results： Compared with normal control group, water content of brain tissue significantly increased at 6 and 12 hours in SAP group（ P 〈0. 05 ） and significantly decreased at 6 and 12 hours in the treated group compared with SAP group （P 〈 0. 05 ）. Compared with normal control group, histopathology score of the rat pancreas, levels of NF-κB p65 mRNA and TNF-α, MDA, the count of leucocytes accumulation and adhesion of the brain tissue, levels of hemodiastase and TNF-α in the blood significantly increased at each time point in SAP group （ P 〈 0. 05 ）.However, when compared with SAP group they significantly decreased at 6 and 12 hours in the treated group（P 〈 0. 05 ）. Conclusion： It is possible that edaravone can clean up free radical, inhibit NF-KB activities, reduce TNF-α or other cytokines in rat brain and inhibit inflammatory response, and play a protective role on cerebral damage caused by SAP in rats.