Objective: To investigate the effects of ulinastatin (UTI) on myocardial injury induced by acute paraquat poisoning.
Methods: Twenty-four Japan white rabbits were divided into control group, model group (37 mg/kg paraquat intraperitoneally once), UTI low dosage group and high dosage group [25 kU×kg(-1)×d(-1) and 50 kU×kg(-1)×d(-1) UTI was intravenously injected respectively for 9 days beginning from 1 week before poisoning] through random number table. Rabbits were sacrificed 24 hours after the last UTI administration. Left ventricle of hearts were harvest, and tissue hydroxyproline (HYP) contents were determined. Matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) transcriptional levels were assayed respectively with reverse transcription-polymerase chain reaction (RT-PCR). Expression levels of MMP-2 in tissue of left ventricle were quantified with immunohistochemistry.
Results: Compared with normal myocardium, acute paraquat poisoning induced elevated HYP (mg/g) content significantly (3.85 ± 0.36 vs. 2.52 ± 0.29, P < 0.05); with RT-PCR and immunohistochemistry, it was shown that both mRNA expression levels and immunohistochemistry score of MMP-2 were much higher (mRNA: 2.07 ± 0.57 vs. 1.00 ± 0.35; immunohistochemistry score: 2.24 ± 0.82 vs. 1.40 ± 0.62, both P < 0.05). TIMP-2 appeared to be down-regulated in mRNA expression level (0.78 ± 0.24 vs. 1.00 ± 0.17, P > 0.05). Disorganized cardiocytes were observed. Compared with paraquat poisoning model, low and high UTI administration produced depression of tissue HYP contents (3.40 ± 0.48, 3.12 ± 0.43 vs. 3.85 ± 0.36, P > 0.05 and P < 0.05). With low or high dosage of UTI reduced mRNA expression levels and immunohistochemical scores of MMP-2 in left ventricle were observed (mRNA: 1.86 ± 0.44, 1.58 ± 0.46 vs. 2.07 ± 0.57, P > 0.05 and P < 0.05; immunohistochemical score: 1.93 ± 0.86, 1.75 ± 0.67 vs. 2.24 ± 0.82, both P < 0.05), and TIMP-2 mRNA level was increased slightly, though there was no significant differences (0.82 ± 0.35, 0.94 ± 0.33 vs. 0.78 ± 0.24, both P > 0.05). Improvements in disordered myocardium were demonstrated.
Conclusions: UTI significantly attenuated myocardial injury induced by acute paraquat poisoning. Its mechanism might be related to a reduction of expression level of MMP-2 in tissue, with a dose-dependent manner.