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1、山西医科大学 硕士学位论文 舒芬太尼后处理对大鼠肠缺血再灌注时肺组织损伤的影响 姓名：郑巧芬 申请学位级别：硕士 专业：麻醉学 指导教师：曹定睿 2011-05-01 山西医科大学硕士学位论文 1 舒芬太尼后处理对大鼠舒芬太尼后处理对大鼠 肠缺血再灌注时肺组织损伤的影响肠缺血再灌注时肺组织损伤的影响 中 文 摘 要 目的目的 通过研究舒芬太尼对肠缺血再灌注大鼠肺组织及血清中肿瘤坏死因子-（TNF-）和肺 组织中核因子-B（NF-B）的影响，探讨舒芬太尼后处理对大鼠肠缺血再灌注时肺组织的影 响及可能机制，以期为临床提供实验依据。 方法方法 将 32 只健康成年雄性 Wistar 大鼠，随机分为
2、4 组：假手术组（S 组）、肠缺血再灌注 组（I/R 组）、肠缺血后处理组（I-post 组）及 1ug/kg 舒芬太尼后处理组（SP 组）。每组各 8 只。假手术组：仅行开腹，分离肠系膜上动脉（SMA）不夹闭；缺血-再灌注组：采用夹 闭肠系膜上动脉 60min 后再灌注 120min 的方法制备肠 I/R 模型； 缺血后处理组： 缺血 60 min 后即刻行 3 个循环的灌注 30 s/阻断 30 s，余同 I/R 组。舒芬太尼后处理组：将 1ug/kg 舒芬 太尼稀释到 0.3ml 在再灌注即刻经股静脉用微量注射泵泵入 0.1ml/30S，期间间断 30s，如此 循环 3 次(共 0.3m
3、l)，余同 I/R 组。于再灌注 120min 时处死 8 只大鼠。HE 染色观察大鼠肺组 织病理改变。采用放射免疫法测定血清及肺组织中 TNF- 的含量；采用免疫组织化学法测定 肺组织中 NF-B 表达水平。 结果结果 （1）HE 检测病理变化：S 组：未发现明显病理变化，肺泡大小均匀，结构完整，壁 薄，未见出血水肿及炎性细胞浸润；I/R 组可见肺泡大小不均，完整性破坏，肺泡腔有蛋白 样渗出物，肺泡壁增厚，间隔增宽，肺间质和肺泡水肿，大量炎细胞浸润、充血、出血明显。 I-post 组、SP 组上述病理变化均较轻，肺泡腔内蛋白渗出减少，肺泡壁增厚、炎细胞浸润 减轻。（2） TNF-、 NF-B
4、 检测： 与 S 组相比， 其余各组 TNF- 增加、 NF-B 表达上调 （05. 0P） ； 与 I/R 组相比，I-post 组及 SP 组 NF-B 表达下调、TNF- 减少（05. 0P）；I-post 组及 SP 组比较上述指标差异无统计学意义（05. 0P）。 结论结论 (1)小肠缺血再灌注可以导致严重的肺损伤。（2）肠缺血再灌注肺损伤机制复杂，其发 生和发展可能与 TNF- 和 NF-B 有关。（3）舒芬太尼后处理对肠缺血再灌注导致的肺损伤 有保护作用， 可抑制肺组织中 NF-B 的表达， 减轻大鼠肠缺血再灌注时血清及肺组织中 TNF- 的含量。 关键词关键词 舒芬太尼; 肺损
5、伤; 缺血再灌注损伤; 肿瘤坏死因子-; 核因子-B 山西医科大学硕士学位论文 2 Effects of Sufentanil post-conditioning on acute lung injury induced ischemia-reperfusion in rats Objective Research sufentanil on intestinal ischemia-reperfusion rat lung tissue and serum tumor necrosis factor- (TNF-) and lung tissue nuclear factor-B (NF-B)
6、, and investigate the effects of Sufentanil post-conditioning (SP) acute lung injury induced by ischemia-reperfusion in rats and possible mechanisms, In order to provide experimental basis for clinical. Methods Thirty-two healthy male Wistar rats were randomly divided into four group (n=8): Sham-ope
7、ration group (S group),I/R group(I/R group),intestinal ischemic Post-conditioning group(I-post group) and 1ug/kg Sufentanil post-conditioning group (SP group).Each group of 8.(1)S group :Superrior mesenteric artery was only isolated but not blocked.(2)I/R group was established by clamping superior m
8、esenteric artery(SMA)for 1 hour and reperfusing for 2 hours.(3) Line immediately after 60 min ischemia and 3 cycles of reperfusion 30 s / block 30 s, more than with the I / R group. (4) The 1ug/kg sufentanil diluted to 0. 3ml immediately after reperfusion through the femoral vein with a syringe pump
9、 pump 0.1ml/30S, during the intermittent 30s, so the cycle 3 times (a total of 0.3ml), than with the I / R Group. The animals were killed at 2 h of reperfusion respectively (n=8). HE dyed observe lung tissue pathology changes in rats. TNF- in the serum and lung tissue were determined using radio-imm
10、unifaction method .Expression of NF-B P65 in the lung tissue was assessed by immunohistichemical method. Results (1) HE detection pathological changes: S group: not found significant pathological changes, alveolar size uniform, complete structure, wall thin, did not see the bleeding edema and inflam
11、matory cells infiltrating; I/R group visible alveolar size is uneven and integrity damage, alveolar exudate of cavity have protein samples, the alveolar wall thickening widened, the interval, interstitial lung and alveolar edema, a lot of inflammatory cell, congestion, bleeding obvious. I-post group
12、 and SP group are lighter the pathological changes, the alveolar lumen protein, the alveolar exudate is reduce thickened wall, inflammatory cell ease. Compared with the sham-operated control group, serum and lung TNF-a lever was increased significantly in the other groups (05. 0P), and NF-kB p65 pro
13、tein in the lung was increased (P0.05). Compared with the I/R group, TNF- in the serum and lung tissues were decreased significantly following Sulfentanil treatment (05. 0P), and the expression of lung NF-B was markedly ameliorated (P0.05).There were no significant difference between I-post group an
14、d SP group(05. 0P). 山西医科大学硕士学位论文 3 Conclusion （1）This study demonstrated that intestinal ischemia-reperfusion l may result in sincerely lung damage.(2) The mechanism of lung injury induced by intestinal ischemia-reperfusion is complicated, and its occurrence and development may be related to TNF- an
15、d NF-KB related.(3) sulfentanil post-conditioning on intestinal ischemia-reperfusion induced lung injury has a protective effect, can inhibit NF-B in lung tissue expression of rat intestinal ischemia and reperfusion reduce the serum and lung tissue content of TNF-. Key words Sulfentanil ; lung injur
16、y ; Ischemia-reperfusion injury; TNF-; NF- B 山西医科大学硕士学位论文 4 英英 文文 缩缩 略略 词词 表表 英文缩写英文缩写 英文全称英文全称 中文全称中文全称 IIR intestinal ischemia reperfusion 肠缺血再灌注损伤 SIRS systemic inflammatory response syndrome 全身炎症反应综合征 MODS Multiple organ dysfunction syndrome 多器官功能障碍综合症 ARDS acute respiratory distresssyndrome 急性呼吸窘迫综合征 TNF- Tumor Necrosis Factor- 肿瘤坏死因子 NF-B nuclear factor kappa-B
