乌司他丁不同给药途径对重症急性胰腺炎模型大鼠治疗作用的研究

目的:探讨乌司他丁经2种给药途径对重症急性胰腺炎(SAP)模型大鼠的治疗作用及机制。方法:50只♂SD大鼠随机分成假手术组(自由饮水)、SAP模型组、阳性对照药萘莫思他组和乌司他丁外周静脉、腹腔动脉给药组共5组,后4组建立SAP模型后分组给药,12h后观察肺、胰腺大体病理及组织学并评分,检测血清淀粉酶、肿瘤坏死因子(TNF-α)、血栓素B2(TXB2)和肺、胰腺组织中髓过氧化物酶(MPO)水平。结果:与SAP模型组比较,各药物组的淀粉酶、TNF-α、TXB2和肺、胰腺组织的MPO及组织学Hughes评分均明显降低(P<0.05);乌司他丁腹腔动脉给药组与其静脉给药组比较,除肺组织的MPO水平更高外(P<0.05),其余各项指标均明显降低(P<0.05)。结论:乌司他丁经腹腔动脉给药比经外周静脉给药对SAP治疗作用更明显,其作用机制可能与其抑制淀粉酶活性、抑制TNF-α、TXB等炎症介质释放以及肺、胰腺组织中的中性粒细胞的浸润及其活化程度有关。

Ulinastatin Administered by Different Routes for Severe Acute Pancreatitis in Rats

OBJECTIVE:To study the curative effect and mechanism of ulinastatin (UTI) administered by two different routes for severe acute pancreatitis (SAP). METHODS: 50 healthy male SD rats were randomly divided into 5 groups: sham operation (SO) group (fed with water ad libitum), SAP model group, positive control(nafamostat) group, ulinastatin peripheral venous perfusion group, and ulinastatin celiac arterial perfusion group. SAP model was established in the latter four groups, and then the rats were treated with corresponding drugs. 12h later, sample tissues were taken from pancreas and lungs for measurement of MPO level and histopathologic observation and the blood samples were collected for measurement of serum amylase, TNF-α and TXB2. RESULTS: Levels of amylase, TNF-α, TXB2, MPO and Hughes histopathologic scores of pancreas and lungs in all drug-treated groups were significantly lower than in SAP group (P<0.05). The content of MPO in lung tissues in ulinastatin celiac arterial perfusion group was higher than in ulinastatin peripheral venous perfusion group (P< 0.05), however, all the other indexes in the former group were lower than in the latter group (P<0.05). CONCLUSION: Administration of ulinastatin by celiac arterial perfusion showed significantly higher efficacy than by peripheral vein perfusion for SAP. The mechanism of ulinastatin for treatment of SAP on rats is possibly associated with its inhibition on the pancreatic enzyme activity and the release of TNF-α, TXB2 and other inflammatory mediators as well as infiltration and the activation degree of neutronphils in pancreas and lungs.