p38MAPK抑制剂对大鼠急性坏死性胰腺炎合并肺损伤的保护作用  

Protective effects of p38MAPK inhibitor on acute necrotizing pancreatitis associated lung injuries in rats

作　　者：许永春[1] 刘枫[2] 龚燕芳[2] 金晶[2] 李兆申[2] 

机构地区：[1]解放军第九四医院消化内科,南昌330002 [2]第二军医大学长海医院消化科

出　　处：《中华胰腺病杂志》2012年第4期257-260,共4页Chinese Journal of Pancreatology

基　　金：全军医药卫生科研基金资助（08MA064）

摘　　要：目的探讨p38MAPK特异性抑制剂SB203580对急性坏死性胰腺炎（ANP）大鼠合并肺损伤的保护作用。方法54只雄性sD大鼠按数字表法随机分为对照组、ANP组和SB203580（干预）组，每组18只。以左旋盐酸精氨酸腹腔注射建立大鼠ANP模型，对照组大鼠腹腔注射等容积生理盐水，干预组在制模前腹腔注射SB203580（用二甲基亚枫溶解配制成10μmol／L）5mg／kg体重。术后3、6、12h分批处死大鼠，取血测淀粉酶、TNF-α和IL-6含量，行胰腺及肺组织病理学检查，计算肺组织湿／干重比，测髓过氧化酶（MPO）含量，RT-PCR法检测中性粒细胞趋化因子（CINC）mRNA表达，蛋白质印迹法检测磷酸化p38MAPK（p-p38MAPK）蛋白表达。结果术后6h，对照组的血淀粉酶、TNF-α和IL-6含量、肺组织湿／干重比、MPO活性、CINCmRNA及p．p38MAPK蛋白表达量分别为（1035±73）U／L、（0．944-0．16）μg／L、（4．77±0．86）μg／L、3．92±0．29、（0．39±0．02）U／g、0．28±0．04、0．09±0．04；ANP组分别为（5848±656）U／L、（3．84±0．32）μg／L、（103．54±15．32）μg／L、4．97±0．47、（1．03±0．08）U／g、0．62±0．06、0．52±0．14；干预组分别为（4259±286）U／L、（1．64±0．21）μg／L、（76．56±11．46）μg/L、4．32±0．34、（0．78±0．05）U／g、0．374±0．04、0．27±0．08。ANP组的各项指标均显著高于对照组，干预组的各项指标均显著低于ANP组，但仍显著高于对照组（P值均〈0．01）。结论SB203580可通过阻断p38MAPK信号通路，在一定程度上减少炎症因子的产生，减轻ANP大鼠胰腺及肺组织损伤。Objective To investigate the protective effects of p38MAPK inhibitor SB203580 on acute necrotizing pancreatitis associated lung injuries in rats. Methods Fifty-four SD male rates were randomly divided into 3 groups, including control group, ANP group, SB203580 group with 18 rats in each group. ANP was induced by intraperitoneal injection of L-arginine solution. Rats in control group were intraperitoneally injected with same amount of saline. Before ANP induction, the rats in SB203580 group received 10 μmol/L SB203580 dissolved by dimethyl sulfoxide at a dose of 5mg/kg weight via intraperitoneal injection. The rats were sacrificed at 3, 6, and 12 h after operation, the serum levels of amylase, TNF-α, IL-6 was determined. Pathological changes of pancreas and lung were observed. The wet/dry （W/D） weight ratio of lung and MPO were measured. CINC mRNA of lungs was determined by RT PCR. Expression of phosphated-p38MAPK （p-p38MAPK） protein was evaluated by Western blotting. Results The serum levels of amylase, TNF-α, IL-6 and wet/dry （W/D） weight ratio of lung, MPO activity , CINC mRNA and p-p38MAPK protein expression of lungs were （ 1035 ± 73 ） U/L, （0.94±0.16 ） μg/L, （ 4.77 ± 0.86 ） μg/L, 3.92 ± 0.29, （ 0.39 ± 0.02 ） U/g, 0.28 ±0.04,0.09 ±0.04 in control group at 6 h after operation, and the corresponding values were （5848 ± 656 ） U/L, （ 3.84 ± 0.32） μg/L, （ 103.54 ± 15.32） μg/L,4.97 ± 0.47, （ 1.03 ±0.08 ） U/g, 0.62 ± 0.06, 0.52 ±0.14 in ANP group, while they were （4259±286） U/L, （ 1.64±0.21 ） μg/L, （76.56 ± 11.46） μg/L, 4.32 ±0.34, （0.78 ±0.05）U/g, 0.37 ±0.04, 0.27 ±0.08 in SB203580 group. The values in ANP group were significantly higher than those in control group, and the values in SB203580 group were significantly lower than those in ANP group, but they were still signifieantly higher than those in control group （P 〈0.01 ）. Conclusions SB203580 may attenuate injury of lung and panereas in ANP by bloeking p38MAPK signal

关 键 词：胰腺炎 急性坏死性 P38丝裂原活化蛋白激酶 SB203580 急性肺损伤 

分 类 号：R576[医药卫生—消化系统]