| 摘要: |
| 目的 观察乌司他丁治疗后梗阻性黄疸大鼠肺的炎性浸润以及组织形态学改变, 探讨乌司他丁对梗阻性黄疸大鼠肺的保护作用及其机制。 方法 通过胆总管结扎来建立梗阻性黄疸大鼠模型。乌司他丁治疗组术后每天给予乌司他丁10万U/kg的剂量腹腔注射给药, 梗阻性黄疸对照组不进行治疗。分别在术后第1、3、7、14天取材, 检测大鼠的肝功能、肺组织病理, 计算干湿比及含水率, 并测定肺通透性指标(伊文思蓝含量)、肺组织中髓过氧化物酶(MPO)活性以及丙二醛(MDA)含量, 免疫组化测定肺组织标本TNF-α和IL-1β表达。 结果 乌司他丁治疗组血清胆红素含量、肺组织干湿比及含水率与梗阻性黄疸对照组相比,差异无统计学意义。而乌司他丁治疗组MPO、MDA及伊文思蓝含量较梗阻性黄疸对照组下降, 差异有统计学意义(P<0.01)。乌司他丁治疗组与梗阻性黄疸对照组比较, 肺间质水肿减轻, 炎性细胞浸润和肺泡内红细胞渗出减少。乌司他丁治疗组第1天和第14天的TNF-α和IL-1β表达均低于同期梗阻性黄疸对照组。 结论 乌司他丁可抑制梗阻性黄疸大鼠致炎因子TNF-α和IL-1β在肺组织中的表达, 降低中性粒细胞浸润并减少氧自由基的产生, 改善肺泡毛细血管通透性, 降低肺内炎症反应。 |
| 关键词: 乌司他丁 梗阻性黄疸 毛细血管通透性 髓过氧化物酶 丙二醛 肺损伤 |
| DOI：10.3724/SP.J.1008.2011.01208 |
| 投稿时间：2011-03-09修订日期：2011-08-20 |
| 基金项目:上海市科技启明星计划(08QA14007), 2009年度天普科研基金. |
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| Protective effect of ulinastatin against cholestasis-associated lung injury in rats |
| ZHU Min1△,HUANG Mei-ying2△,CHEN Wei-xin3,TANG Zhao-hui4*,YANG Li-qun1,YU Wei-feng1 |
(1. Department of Anesthesia & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical Univesity, Shanghai 200438, China;
2. Liyang Health Centre of Ninghai, Ningbo 315602, Zhejiang, China;
3. Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, China;
4. Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, China
△Co-first authors.
*Corresponding author.) |
| Abstract: |
| Objective To observe the inflammatory infiltration and morphological changes of lung after treatment with unlinastatin in cholestatic rats, so as to study the protective effect of unlinastatin on the lung of cholestatic rats. Methods Rat obstructive jaundice models were established by bile duct ligation (n=48). Ulinastatin (UTI, 100 000 U/kg) was injected intraperitoneally after operation. The lung tissues were collected at day 1, 3, 7, and 14 after operation. The hepatic function and pulmonary pathology were observed after treatment; dry/wet ratio and water content were calculated. The parameters for alveolar capillary permeability, content of myeloperoxidase (MPO), and activity of malondialdehyde (MDA) were also assessed. Expression of TNF-α and IL-1β was examined by immunohistochemical method. Results The serum bilirubin,dry to wet ratio and water content of the lung tissues were not significantly different between UTI group and jaundice group(P>0.05). The levels of evans blue dyes (EBD), MPO, and the activity of MDA in UTI group were significantly lower than that in the jaundice group and UTI groups at the same time points (P<0.05). The pulmonary histology showed alleviated edema, less neutrophil infiltration and RBC in alveolar space in UTI group compared to jaundice group. The pulmonary expression of and IL-1β and TNF-α was significantly lower in UTI group than that in jaundice group on day 1 and day 14 (P<0.01). Conclusion Ulinastatin can inhibit pulmonary expression of pro-inflammatory cytokines TNF-α and IL-1β and decrease MPO activity and MDA levels in bile duct-ligated rats, thus improving the permeability of the pulmonary capillary membrane in obstructive jaundice rats and decreasing the pulmonary inflammatory reactions. |
| Key words: ulinastatin obstructive jaundice capillary permeability myeloperoxidase malondialdehyde lung injuries |
