Mechanism research and effect of ulinastatin in the brain tissue injury of acute hydrogen sulfide intoxicated rats

Abstract

To observe the effect of Ulinastatin (UTI) in the dynamic changes of aquaporin 4 (AQP4) and cyclooxygenase-2 (COX-2) in the brain tissue injury of acute hydrogen sulfide (H2S) intoxicated, to explore the Mechanism of brain tissue injury of acute H2S-intoxicated and the protection effect of UTI. A total of 96 SD rats of clean grade were divided randomly into four groups: normal control group (NS group, n=8) , UTI control group (UTI group, n=8) , H2S-intoxicated model group (H2S group, n=40) , UTI treatment group (H2S+UTI group, n=40). The H2S group and H2S+UTI group were exposed to H2S (284 mg/m(3)) by inhalation for 1 h, then H2S+UTI group was intraperitoneally exposed to UTI at the dose of 10(5) U/kg for 2 h, H2S group and H2S+UTI group were sacrificed at 2, 6, 12, 24 and 48 h after exposure, respectively. Remove the brain tissue, observe the rats behavioral changes at each time points. The mRNA expression of AQP4、COX-2 and NSE in the brain tissue were measured by RT-PCR method, and the protein expression of AQP4、COX-2 and NSE in the brain tissue were detected by immunohistochemical Streptavidin-perosidase method. Pathological changes of brain tissue were observed by lightmicroscope. 1、Nerve cells in the H2S group rats had edema, degeneration, focal inflammatory cell infiltrate, capillary hyperplasia, expansion. Compared with NS group, the cerebral NSE mRNA and protein expression at each time point in H2S group after exposure were significantly increased (P<0.01). 2、Compared with NS group, the cerebral AQP4 and COX-2 mRNA and protein expression at each time point in H2S group after exposure were significantly increased (P<0.01). 3、The degree of brain damage was significantly decreased in H2S+UTI group than that in H2S group. Compared with H2S group, the cerebral NSE mRNA and protein expression at 6, 12, 24 and 48 h in H2S+UTI group after exposure were significantly decreased (P<0.01) , no significantly difference at 2h (P>0.05). 4、Compared with the H2S group, the cerebral AQP4 and COX-2 mRNA and protein expression at 6, 12, 24 and 48 h in H2S+UTI group after exposure were significantly decreased (P<0.01) , slightly decreased at 2 h. The mechanism of brain injury of acute hydrogen sulfide intoxicated associated with abnormal expression of the cerebral AQP4, COX-2 levels. Intervention of UTI can reduce the cerebral AQP4 and COX-2 levels after hydrogen sulfide intoxicated, reduce the degree of brain injury.