DMTU对大鼠SAP致肺损伤的保护作用

目的研究二甲基硫脲（dimethylthiourea，DMTU）对大鼠急性重症胰腺炎（severe acute pancreatitis，SAP）肺损伤是否具有保护作用，为临床治疗SAP所致肺损伤提供新思路。方法将18只雄性Wistar大鼠随机分为治疗a组（注射DMTU a组）、对照a组（注射生理盐水a组）和假手术a组，每组6只。在存活实验中，将60只Wistar大鼠随机分为3组（治疗b组、对照b组和假手术b组）每组包括20只大鼠。应用逆行胰胆管穿刺注射牛黄胆酸钠制备SAP大鼠模型，造模成功后对治疗组大鼠腹腔注射DMTU（500 mg/kg体质量、150 mg/kg体质量，2次/d）。其余各组大鼠均腹腔注射生理盐水（1 ml/100 g体质量）。术后观察72 h后通过心脏放血处死大鼠，取走肺及胰腺组织。观察大鼠肺脏组织的髓过氧化酶（MPO）活性、丙二醛（MDA）水平和组织学变化及DMTU对其的影响。在存活实验中，观察各组大鼠的存活情况。结果对照a组的MPO活性增强，MDA水平提高；DMTU可以明显降低肺组织的MPO活性和MDA水平，同时DMTU可以减轻大鼠肺组织的病理损害而没有改善胰腺组织的病理损害；术后72h内各时间点治疗b组的大鼠生存率均比对照b组高。结论各种炎症介质、细胞因子及氧自由基参与了SAP的病理生理过程。DMTU可直接降低SAP大鼠肺组织MPO活性和MDA水平而减轻组织脂质过氧化和肺组织病理损害，最终可以降低死亡率。

Protection of Dimethylthiourea against lung injury induced by severe acute pancreatitis in rats

Objective To observe the protective effects of dimethylthiourea （DMTU） on lung injury induced by severe acute pancreatitis （SAP） in rats. Methods Eighteen male Wistar rats were divided randomly into three groups： DMTU treating group, control group and sham operation group randomly. In the survival experiment, a total of 60 rats were divided into three groups and each group consisted of twenty rats. Sodium taurocholate were injected into the pancreatic bile duct to induce SAP model. Rats in DMTU treating group were treated with an intraperitoneal injection of DMTU 500 mg/kg （ body weight） on the first day and followed by 150mg/kg （body weight） twice a day for next 2 days. The other two groups were given intraperitoneal injection of physiological saline （ 1 ml/100 g body weight） instead. The rats were sacrificed by bleeding from the heart after 72 h and their lungs and pancreas were removed. The levels of myeloperoxidase （MPO） and malondialdehyde （MDA） in lungs were measured and histological changes in lungs and pancreas were observed. In the survival experiment, the survival information was documented. Results The survival rate in DMTU treating group was higher than that in the control group. The levels of MPO and MDA in lungs were significantly higher in control group （ P 〈 0.05 ） indicating that DMTU treatment decreased the levels of MPO and MDA in lungs. DMTU suppressed the histological changes in lungs but had no effect on pancreas. Conclusion It is postulated that mediators of inflammation, cytokines and oxygen free radicals participate in the process of pathological changes in SAP. DMTU might decrease MPO activity and MDA level then attenuate lipid peroxidation and histological injury in lungs of SAP directly. DMTU might reduce the fatality of SAP rats.