Effect of ulinastatin, a human urinary protease inhibitor, on heatstroke-induced apoptosis and inflammatory responses in rats

Ulinastatin has been demonstrated to protect against heatstroke by reducing cerebral ischemia and damage in rats. In order to extend these observations, apoptosis and systemic inflammatory responses were assessed in rats treated with ulinastatin prior to the initiation of heatstroke. Following the onset of heatstroke, histological analysis revealed that the hippocampal tissues displayed edema and damage. In addition, upregulation of malondialdehyde, inducible nitric oxide synthase (iNOS) and reactive oxygen species and downregulation of superoxide dismutase were observed compared with the respective levels in the control group. Furthermore, TUNEL staining and western blotting assays indicated that heatstroke induced cell apoptosis by increasing the Bax/Bcl-2 ratio and caspase-3 levels, and upregulating the protein expression levels of nuclear factor-κB, cyclooxygenase-2 and iNOS. However, the injury induced by heatstroke was significantly inhibited by ulinastatin pretreatment at doses of 5,000 and 10,000 IU/kg. Survival analysis of the rats subjected to heatstroke demonstrated that rats treated with ulinastatin at a dose of 10,000 IU/kg lived longer than those that did not receive ulinastatin treatment. These observations indicate that ulinastatin may protect against heatstroke by reducing apoptosis and systemic inflammatory responses.