Ulinastatin attenuates paraquat-induced myocardial injury / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effect of ulinastatin (UTI) on endogenous antioxidant systems in the process of myocardial oxidative stress injury induced by paraquat (PQ),so as to elucidate UTI protecting cadiocytes against PQ-induced injury.Methods Thirty Japan white rabbits were randomly (random number) divided into A,a sham control group; B,PQ intoxication model group and C,D,E,three UTI groups as per different dosages of UTI given.PQ (30 mg/kg) was administered by intraperitoneal route to the rabbits of PQ intoxication model and rabbits of three UTI groups.UTI in doses of 15 000,30 000,50 000 U/kg was administered intravenously every day to the rabbits of three UTI groups respectively for 7 days after PQ intoxication.After the rabbits were sacrificed with 10％ chloral hydrate,left ventricles of rabbits were taken.Histomorphological changes of myocardium were observed by using HE staining.Hydroxyproline was measured by alkaline hydrolysis method,myocardial oxidative stress evaluated by 4-hydroxy-2-nonenal (4-HNE) immunohistochemistry staining,transcription levels of transforming growth factor-β1 (TGF-β1),adiponectin,peroxisome proliferator-activated receptor α (PPAR-α),AMP-activated protein kinase-β1 (AMPK-β1),uncoupling protein-1 (UCP-1) were assayed with reverse transcriptionpolymerase chain reaction (RT-PCR).The differences between two groups were analyzed by t test ; for multiple comparisons,data were analyzed by One-Way ANOVA followed by Dunnett' s post hoc test; for two and multiple ranked data comparisons,Mann-Whitney U test and Kruskal-Wallis test were used,and Spearman rank correlation analysis was used to investigate the correlation between UTI dose and transcription levels of endogenous antioxidant.Results Compared with group A,left ventricular cadiocytes in group B became swelled and disarranged,concentration of tissue HYP was elevated to (2.37 ± 0.49),P =0.001;scores of 4-HNE and TGF-β1 mRNA expressions were all upregulated (both P =0.001).Compared with group B,disordered myocytes in UTI treated groups tended towards normal,4-HNE scores in group D and group E descended respectively to (1.83 ± 0.53) and (1.70 ± 0.47),both P =0.001,HYP concentration reduced to (3.51 ±0.39) μg/mg and (3.29 ±0.37) μg/mg (P =0.002; P =0.001),and expressions of TGF-β1 mRNA in these two groups were decreased (both P =0.001).Transcription levels of four endogenuous antioxidant components,adiponectin,PPAR-α,AMPK-β1 and UCP-1,were all augmented in the group E with high dose UTI.The mRNA expressions of these four components positively correlated with the dose of UTI in the myocardium of PQ intoxicated rabbits.Conclusions UTI could protect myocardia against PQ-induced injury by increasing endogenous antioxidant systems.