摘要
目的观察p38蛋白激酶（p38MAPK）抑制剂对大鼠急性胰腺炎肺损伤（LI）肺内细胞间黏附分子（ICAM）-1表达和肺微血管通透性的影响。方法SD大鼠36只，假手术组12只；5％的牛黄胆酸（0．1ml／100g）逆行注射到sD大鼠的胰胆管内，造成重症急性胰腺炎（SAP）；分为SAP组12只和p38MAPK抑制剂组（SB203580，0．5mg／kg，静脉注射）12只。各组在3、6、12h分别剖杀大鼠，检测肺组织的含水量、肺组织髓过氧化物酶（MPO）；免疫组织化学检测肺组织p38MAPK的表达；逆转录-聚合酶链反应（RT．PCR）检测肺组织ICAM-1mRNA表达水平；检测肺微血管通透性Balf/Serum FITC比率；光镜下检测肺组织组织损害。结果假手术组肺组织含水量、MPO、肺组织病理评分、ICAM-1mRNA分别为3．41±0．05、1．48±0．10、0和0．48±0．03；SAP组在3、6、12h肺组织含水量分别为为3．77±0．12、3．87±0．11和4．03±0．05，SB治疗组分别为3．53±0．07、3．57±0．05和3．69±0．09，SAP组MPO分别为2．17±0．42、4．65±0．26和7．70±0．01，SB治疗组分别为1．72±0．14、2．46±0．29和5．63±0．15；SAP组肺组织病理评分分别为3．16±0．03、5．33±0．05和7．18±0．02，SB治疗组分别为3．12±0．02、5．26±0．03和7．13±0．02；；SAP组ICAM-1mRNA在6、12h表达为1．45±0．04和1。65±0．06，SB治疗组分别为1．19±0。06和0．96±0．05。SAP组和SB治疗组上述指标较假手术组升高（P〈0．05），但SB治疗组较SAP组下降（P〈0．05）；而且肺组织p38MAPK表达和ICAM-1mRNA表达一致，在12h达高峰。结论急性胰腺炎肺损伤可能与肺组织中p38MAPK和ICAM-1mRNA过度表达有关；p38MAPK抑制剂可抑制肺内ICAM-1表达，降低肺微血管通透性，减轻急性胰腺炎肺损伤。
Objective To investigate the effects of p38 mitogen-activated protein kinase （p38 MAPK） inhibitor on intercellular adhesion molecule （ICAM） expression and microvascular permeability of lung injury in rats with severe acute pancreatitis （SAP）. Methods Sixty Sprague Dawley rats were randomly divided into sham operation group, SAP group and SB203580 treatment group （SB group）. The rats of SB group were injected with SB203580 （0. 5 mg/kg） via the femoral vein. The rats were sacrificed at 3rd, 6th and 12th h after operation. The lung myeloperxidase （MPO） activity, water content of lung tissue and ratio of microvascular permeability of lung were determined. The expression of p38 MAPK protein and mRNA in the lung tissues was detected by immunohistochemical technique and reverse transcription-polymerase chain reaction （RT-PCR） respectively. Lung tissue samples were stained with hematoxylin and eosin for histopathological examination. Results Water content of lung tissue, the levels of MPO activity, lung pathologic score, the expression of ICAM-1 mRNA in the lung tissues in sham operation group were 3.41 ± 0. 05, 1.48 ±0. 10, 0 and 0. 48 ±0. 03 respectively. Water content of lung tissue at the 3rd, 6th and 12th h after operation in SAP group was 3.77 ±0. 12, 3. 87 ±0. 11 and 4. 03 ±0. 05 respectively, and that in SB group was 3.77 ±0. 12, 3. 87 ±0. 11 and 4. 03 ±0. 05 respectively. The levels of MPO activity in SAP group at each time point were 2. 17 ±0. 42, 4. 65 ±0. 26 and 7.70 ±0. 01 respectively, and those in SB group were 2. 17 ±0.42, 4. 65 ±0. 26 and 7.70 ±0.01 respectively. Lung pathologic score in SAP group at each time was 3. 16 ±0. 03, 5. 33 ±0. 05 and 7. 18 ±0. 02 respectively, and that in SB group was 3. 16 ±0. 03, 5. 33 ± 0. 05 and 7. 18 ±0. 02 respectively. ICAM-1 mRNA in SAP group at the 6th and 12th h was 1.45 ±0. 04 and 1.65 ±0. 06, and that in SB group was 1.19 ±0. 06 and 0. 96 ±0. 05, respectively. Those in the SAP and SB group were increased more significantly than those in the sham operation group （P 〈0. 05 ）. Those in the SB group were more significantly reduced in SB group than those in SAP group at the 3rd, 6th and 12th h （P 〈0. 05）, and the expression of ICAM-1 mRNA reduced at the 6th and 12th h （P 〈 0. 05）. Conclusion The activation and overexpression of p38 MAPK and ICAM-1 mRNA in the lung tissues may be one of the reasons for lung injury in SAP, and SB203580 can be used to treat the SAP associated lung injury through downregulating the expression of p38 MAPK and ICAM-1 mRNA in the lung tissues and decreasing microvascular permeability of pulmonary.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2010年第4期471-473,共3页
Chinese Journal of Experimental Surgery
基金
河南省科技攻关计划资助项目（200903126）
