RESUMEN
Objective: To explore the role of c-Jun NH2 terminal kinase (JNK) activation and JNK-mediated apoptotic signal pathway in intestinal ischemia/reperfusion (II/R) in mice. Methods: C57BL/6 mice were randomly divided into sham-operated group (n = 6) and II/R groups (n = 36); the latter was further divided according to time after perfusion (0,0. 5,1,4,6 and 12 h). Animal II/R model was established by clamping the superior mesenteric artery (SMA) for 40 min followed by reperfusion. Animals in the sham-operated group received no clamping. Animals in the two groups were sacrificed at defined time points, and the expression of JNK, phosphorylation (phospho-) JNK, cleaved caspase-3,Bcl-2 and Bax protein in the intestinal tissue was examined by Western blotting analysis, and the pathological changes of ileum tissue were observed under optical microscope. Results: Most severe intestinal injury was found at the early stage of reperfusion, and the intestinal tissues almost recovered 12 h later. The phospho-JNK in the intestine was significantly elevated within 1 h after II/R compared with sham group (P<0. 01). Cleaved caspase-3 was significantly increased in II/R group at 0. 5 h, 1 h after reperfusion compared to sham group (P<0. 01); the expression of Bcl-2 protein in II/R group was significantly decreased compared with the sham-operated group (P<0. 01), and there was no significant difference in Bax expression between different groups. Conclusion: JNK phosphorylation plays an essential role in the intestinal damages induced by II/R,possibly through down-regulating Bcl-2 protein expression and caspase-3 dependent apoptosis pathway.
RESUMEN
Objective To investigate the possible role of p38 mitogen-activated protein kinase (MAPK) in lung injury following intestinal ischemia reperfusion (II/R) in mice. Methods Intestinal ischemia/reperfusion was induced by occluding the superior mesenteric artery for 45 min followed by 6 h reperfusion. C57BL/6 mice were randomly divided into sham-operated group (sham group), II/R group and II/R plus SB239063 treatment (SB239063 group), n = 6/group. SB239063 (3 mg/kg), a novel second-generation p38 MAPK inhibitor, was administered intraperitoneally one hour before clamping. Pulmonary p38 MAPK and phospho-p38 MAPK protein were measured by Western blotting analysis. Gene expression of TNF-α and IL-1β in the lung was analyzed by RT-PCR. The lung pathology was observed by optical microscope. Results Compared with the sham- operated group, pulmonary p38 MAPK activation was significantly increased 6 h after II/R (P<0. 01), whereas SB239063 could markedly attenuate p38 MAPK activation in lung tissue (P<0. 05). In addition, the increased TNF-α and IL-1β mRNA levels induced by II/R in lungs were significantly blocked by inhibiting p38 MAPK activation (P<0. 05). SB239063 treatment ameliorated the pathologic lung injury induced by II/R. Conclusion p38 MAPK plays an important role in lung injury induced by intestinal ischemia reperfusion (II/R) in mice, and inhibition of p38 MAPK activation prevents lung injury following II/R in mice.