Mild hypothermia regulates aquaporin 4 expression in brain tissue of rats with cardiopulmonary resuscitation and reduces brain edema through p38 mitogen-activated protein kinase signaling pathway

Abstract

To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in the expression of aquaporin 4 (AQP4) in brain tissue of rats with cardiopulmonary resuscitation (CPR) during mild hypothermia. Forty-eight healthy male Sprague-Dawley (SD) rats were divided into sham operation group, normal temperature group and mild hypothermia group according to random number table method, with 16 in each group. The rat model of cardiac arrest-cardiopulmonary resuscitation (CPR) was established by asphyxia method. The sham operation group only experienced venous catheterization and tracheal intubation. The mild hypothermia group was treated with hypothermia 0.5 hours after restore of spontaneous circulation (ROSC, maintaining esophageal temperature at 32-34 centigrade); the normal temperature group was treated at room temperature after ROSC (maintaining esophageal temperature at 36-38 centigrade). Brain tissue was harvested at 6 hours after ROSC, and histopathological changes were observed by hematoxylin-eosin (HE) staining. The water content of brain tissue was determined by dry-wet specific gravity method. The protein expressions of phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK), p38MAPK and AQP4 in brain tissue were determined by Western Blot. Compared with the sham operation group, the nerve cells in the normal temperature group were reduced in size, cytoplasmic loosening, nuclear pyknosis, and in apoptotic body formation, water content of brain tissue was significantly increased [(83.64±2.53)% vs. (77.95±0.94)%, P < 0.05], the protein expressions of p-p38MAPK, p38MAPK, AQP4 were significantly increased (p38MAPK/β-actin: 1.010±0.217 vs. 0.427±0.090, p-p38MAPK/p38MAPK: 0.451±0.172 vs. 0.191±0.141, AQP4/β-actin: 3.129±0.754 vs. 1.598±0.464, all P < 0.05). Compared with the normal temperature group, the degree of necrosis of nerve cells in the mild hypothermia group was reduced, the water content of brain tissue was significantly decreased [(80.49±2.05)% vs. (83.64±2.53)%, P < 0.05], the protein expression of p38MAPK, p-p38MAPK and AQP4 in brain tissue were significantly decreased (p38MAPK/β-actin: 0.590±0.162 vs. 1.010±0.217, p-p38MAPK/p38MAPK: 0.298±0.076 vs. 0.451±0.172, AQP4/β-actin: 2.061±0.340 vs. 3.129±0.754, all P < 0.05). Mild hypothermia may regulate the expression of AQP4 in brain tissue of CPR rats through p38MAPK signaling pathway, and reduce brain edema, thereby exerting brain protection.