重症急性胰腺炎模型大鼠肺组织血红素加氧酶-1的表达及意义

目的：探讨重症急性胰腺炎（SAP）肺组织血红素加氧酶-1（HO-1）活性的变化和意义以及乌司他丁的干预作用。方法：将大鼠随机分为正常对照组，SAP模型组，HO-1诱导剂组和乌司他丁组，后3组大鼠用5%牛磺胆酸钠逆行胆胰管注射制法诱导SAP模型，其中HO-1诱导剂组和乌司他丁组于造模后5 min分别静脉注射牛血晶素和乌司他丁，而SAP模型组给予等体积生理盐水。于术后不同时间点观察各组的肺组织病理变化，检测肺组织湿/干重比、髓过氧化物酶（MPO）活性及HO-1的表达量。结果：除正常对照组外，各组均出现明显的肺损伤，但2个治疗组的肺损伤情况明显好于SAP模型组。与正常对照组比较，各组术后肺组织湿/干重比、肺组织MPO活性及HO-1的表达量均明显升高（均P<0.05），且基本呈随时间延长的增加趋势；与SAP模型组比较，2个治疗组肺组织湿/干重比、MPO活性降低，HO-1的表达量升高（均P<0.05）；2个治疗组间比较，以上指标的差异均无统计学意义（均P>0.05）。相关分析显示，SAP大鼠肺组织HO-1活性与肺组织MPO活性和湿/干重比均呈明显负相关（r=-0.79，-0.77，均P<0.05）。结论：SAP大鼠肺组织HO-1活性增高，应用HO-1诱导剂增加肺组HO-1活性能减轻SAP急性肺损伤，乌司他丁对SAP急性肺损伤保护作用也可能部分与升高HO-1活性有关。

Heme oxygenase 1 expression in lung tissues in rats with severe acute pancreatitis and its significance

Objective: To investigate the alteration in heme oxygenase 1 (HO-1) activity in lung tissues from rats with severe acute pancreatitis (SAP) and its significance, as well as the influence of ulinastatin intervention. Methods: Rats were randomly divided into normal control group, SAP model group, HO-1 inducer treatment group and ulinastatin treatment group. Rats in the latter 3 group underwent retrograde cholangiopancreatic duct injection of 5% sodium taurocholate to elicit SAP model, and then rats in HO-1 inducer treatment group and ulinastatin treatment group were intravenously injected with bovine hemin or ulinastatin at 5 min after SAP model induction respectively, while those in SAP model group were injected with normal saline instead. On different time points after operation, in each group of rats, the pathological changes in the lung tissues were assessed, and the wet-to-dry lung weight ratio as well as the myeloperoxidase (MPO) activity and HO-1 expression in the lung tissues were determined. Results: Except in the normal control group, rats in all other groups exhibited obvious lung injury, which in the two treatment groups was obviously milder than that in SAP model group. Compared with normal control group, the wet-to-dry lung weight ratio, and pulmonary MPO activity and HO-1 expression in all the remaining groups were significantly elevated (all P<0.05), with a basically time increasing trend. Compared with SAP model group, the wet-to-dry lung weight ratios and pulmonary MPO activities were significantly decreased, while lung HO-1 expressions were significantly increased in the two treatment groups (all P<0.05). No statistical difference was noted in any of the parameters between the two treatment groups (all P>0.05). The correlation analysis revealed that there was a significant correlationship between HO-1 expression in the lung tissue and pulmonary MPO activity or wet-to-dry lung weight ratio in SAP rats (r=–0.79 and –0.77, both P<0.05). Conclusion: HO-1 activity is increased in rat lung tissue during SAP, and its enhancement through using HO-1 inducer can alleviate the SAP-induced acute lung injury. The protective effect of ulinastatin against SAP-induced acute lung injury may be partially associated with promotion of HO-1 activity.