ω-3多不饱和脂肪酸对大鼠急性胰腺炎炎性介质及p38丝裂原活化蛋白激酶影响  

Effect of ω-polyunsaturated fatty acids on inflammatory mediators and p38 mitogen-activated protein kinase in rats with severe acute pancreatitis

作　　者：王冬冬[1] 刘红山[2] 岳学良[2] 

机构地区：[1]新乡医学院 郑州大学人民医院(河南省人民医院)肝胆胰腺外科,河南453003 [2]郑州大学人民医院(河南省人民医院)肝胆胰腺外科

出　　处：《中华实验外科杂志》2015年第5期1066-1068,共3页Chinese Journal of Experimental Surgery

基　　金：河南省科技厅基础与前言研究项目（122300410055）

摘　　要：目的 观察ω-3多不饱和脂肪酸（ω-PUFA）对大鼠急性胰腺炎炎性介质及其p38丝裂原活化蛋白激酶（p38MAPK）的影响.方法 150只SD大鼠,体质量220～ 260 g,注入3.5％牛磺胆酸（60 μl/min）.建模成功后,随机分为重症急性胰腺炎（SAP）对照组（SAP组）、传统肠内营养组（EN组）和加入ω-3PUFA肠内营养组（ω-EN组）各50只.EN组采用能全力.ω-EN组加入ω-PUFA3 g/kg.各组大鼠能量摄入均为126 kJ/（kg·d）.建模后24h内,各组均经颈内静脉以400 ml/（kg·d）输入平衡液,建模后24 h后,开始分别行肠内营养,输注速度控制在12 ml/（kg·h）,应用14 d.EN和ω-EN组营养液第2天输入日需总量的1/3,第3天输入1/2,不足量由静脉营养补充,从第4天开始全量肠内营养支持.各组总液体量入量相等.基础治疗：自建模成功后,每组大鼠腹部皮下注射善宁6 μg/（kg·d）作为基础治疗,每日分3次给药.于实验第1、4、7、14天分别经分批处死大鼠：检测血淀粉酶、采用酶联免疫吸附试验（ELISA）检测细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）,电镜下检测胰腺组织;免疫组织化学检测大鼠胰腺组织p38MAPK的表达,并计算大鼠14 d的生存率.结果 SAP组各时段血清TNF-α显著升高,IL-10降低,到4d时达峰值,TNF-α[（257.40±4.52） ng/L],IL-10[（3.40 ±4.52） ng/L],胰腺组织p38MAPK的表达显著升高;用药后,EN组及ω-EN组TNF-α显著降低,EN组[（207.40±0.65） ng/L],ω-EN组[（96.51±0.92） ng/L];IL-10升高,EN组[（9.40 ±0.61） ng/L],ω-EN组[（4.35±1.91） ng/L],与SAP组比较差异有统计学意义（P＜0.01）,胰腺组织p38MAPK的表达也显著减少;SAP组大鼠到7d时,全部死亡,EN组及其ω-EN组全部成活.结论 ω-PUFA的治疗作用之一是可能抑制大鼠急性胰腺炎p38MAPK的表达,从而减少炎性介质的释放来实现.Objective To investigate the effects of ω-polyunsaturated fatty acids （ω-PUFA） on the inflammatory mediators and p38 mitogen-activated protein kinase （p38MAPK） in rats with severe acute pancreatitis （SAP）.Methods 150 Sprague Dawley rats were randomized into SAP group,enteral nutrition （EN） group and ω-PUFA EN group.SAP model was induced by low pressure retrograde infusion of biliopancreastic duct with 3.5% sodium taurocholate solution （0.1 ml/100 g）.The rats were sacrificed at 1st,4th,7th and 14th day after operation.The serum amylase （AMY）,tumor necrosis factor-α （TNF-α） and interleukin （IL）-10 were determined.The expression of p38MAPK in the pancreas was detected by immunohistochemistry.Pancreas tissue samples were stained with hematoxylin and eosin for histopathological evalution.Results The serum TNF-α was significantly increased,and IL-10 was significantly reduced in SAP group at all time points,and they reached the peak at 4th day after operation [for TNF-α,（257.40 ±4.52） ng/L;for IL-10,（3.40 ±4.52） ng/L],and the expression of p38MAPK the pancreatic tissue was significantly increased.After treatment,serum TNF-α was significantly reduced in EN group [（207.40±0.65） ng/L],and ω-PUFA EN group [（96.51 ±0.92） ng/L],and IL-10 increased in EN group [（9.40 ±0.61） ng/L],and ω-PUFA EN group [（4.35 ± 1.91） ng/L] as compared with SAP group （P 〈 0.01 for all）.The p38MAPK expression in pancreatic tissues was also significantly reduced in EN group andω-PUFA EN group.The animals in SAP group were died at 7th day after operation,and those in EN group and ω-PUFA EN group survived.Conclusion The activation and over-expression of p38MAPK in pancreas tissue may be one of the reasons for SAP,and ω-PUFA can be used to treat the SAP through downregulating the expression of p38MAPK in the pancreas tissue.

关 键 词：急性胰腺炎 Ω-3多不饱和脂肪酸 肿瘤坏死因子-Α 白细胞介素-10 

分 类 号：R576[医药卫生—消化系统]