protective effects of ulinastatin on cardiac dysfunction in mice with heat stroke and its mechanism

Objective To examine the effects of ulinastatin (UTI) on cardiac dysfunction in mice with heat stroke and its possible mechanism. Methods 20 mice were divided into four groups randomly: room temperature plus normal saline (Sham+NS), room temperature plus UTI (Sham+UTI), heat stress plus normal saline (HS+NS), heat stress plus UTI (HS+UTI), 5 each. 105U/kg UTI was delivered by intraperitoneal injection before the onset of the heat stress. Room temperature groups were housed at room temperature (23.0±0.5℃), while heat stress groups were kept in an incubator at 36.5±0.5℃ and humidity of 65.0%±2.0%. The rectal temperature (Tr) reaching 42℃ was taken as severe heat stroke, and the time in two heat stress groups was recorded. The mice were transferred to the room temperature (23.0±0.5℃) for natural cooling after the heat stroke onset. 6 hours after the treatment, cardiac output (CO) was ultrasonographically detected, the myocardium was separated for histopathological examination and the expression of total p38 and phosphorylated p38 (p-p38) was determined by Western blotting. Results The time to reach 42℃ in HS+UTI group was significantly prolonged (P=0.044). Compared with the Sham+NS group, the CO in HS+NS and HS+UTI group decreased significantly (P=0.017), and the score of myocardial inflammation (P<0.001) and p-p38/p38 ratio (P<0.001) increased. The CO was significantly higher in HS+UTI group than in HS+NS group (P=0.030), and the score of myocardial inflammation (P<0.001) and p-p38/p38 ratio (P=0.001) were significantly lower. Conclusion Ulinastatin might improve the cardiac function in mice with heat stroke by decreasing the p-p38 and alleviating the inflammation response. DOI: 10.11855/j.issn.0577-7402.2017.04.04