Effects of p38 MAPK inhibitor on adhesion molecule expression and microvascular permeability of lung injury in rats with severe acute pancreatitis

Objective To investigate the effects of p38 mitogen-activated protein kinase (p38 MAPK) inhibitor on intercellular adhesion molecule (ICAM) expression and microvasctdar permeability of lung injury in rats with severe acute pancreatitis (SAP). Methods Sixty Sprague Dawley rats were ran-domly 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-polymer-ase 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 patho-logic 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 de-creasing miemvaseular permeability of pulmonary. Key words: Acute pancreatitis;  p38 Mitogen-activated protein kinases;  Lung injury;  Adhe-sion molecule