丙泊酚对肺缺血再灌注损伤大鼠肺上皮细胞凋亡的影响

1、丙泊酚对肺缺血再灌注损伤大鼠肺上皮细胞凋亡的影响华中科技大学同济医学院附属协和医院詹美俊 张诗海 姚尚龙作者单位：430022 武汉 华中科技大学附属协和医院麻醉科 目的 探讨丙泊酚对肺脏缺血再灌注大鼠肺上皮细胞凋亡的影响。方法 采用大鼠肺原位热缺血模型, 缺血1h。 170只大鼠随机分为缺血再灌注组 (I/R组,n70), 丙泊酚再灌注组 (P组，n70) 以及相同机械通气时间的假手术组（S组，n30）。按照再灌注时间的不同，分别于缺血1h 、再灌注0.5h、1h、2h、4h时间点(或假手术组相应时间点)测定各组动脉血氧分压(Pa02)、支气管肺泡灌洗液(BALF)中中性粒细胞( PMN)百

2、分比、蛋白浓度, 以及肺组织丙二醛（MDA）、超氧化物歧化酶（SOD）含量和肺湿干重比值(W/D)。采用原位末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）技术，测定肺缺血再灌注下(或假手术组相应时间点)肺上皮细胞凋亡指数。结果 在缺血1h时间点(或假手术组相应时间点)三组间各种指标无显著差异性(P0.05)。再灌注后,与S组相比, 相同时间点的I/R组和P组PMN百分比、蛋白浓度、MDA含量及凋亡指数均有所升高且具有显著差异性（P0.05）；而Pa02 和SOD含量有所降低且具有显著差异性（P0.05）。再灌注后,与I/R组相比, 相同时间点的P组PMN百分比、蛋白浓度

3、、MDA含量及凋亡指数均有所降低且具有显著差异性（P0.05）; 而SOD含量在再灌注后较I/R组有所升高且在再灌注4h时具有显著差异性(P0.05) 。相关性分析显示，无论I/R组还是P组其凋亡指数与W/D均呈高度正相关（P0.01）。结论 丙泊酚对大鼠缺血再灌注肺损伤具有保护作用,可能与其减少缺血再灌注时氧自由基的产生,抑制再灌注损伤肺组织中中性粒细胞的聚集以及抑制肺上皮细胞凋亡有关。关键词 缺血; 再灌注损伤; 肺; 凋亡; 丙泊酚Relationship of propofol in attenuating lung injury after ischemia-reperfusion

4、with apoptosis in ratsZhan Mei-jun Zhang Shi-hai Yao Shang-long (Department of Anaesthesiology, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, 430022 Wuhan , China)Objective To observe the relationship of propofol attenuating lung injury after reperfusion with

5、 apoptosis in rats. Methods The model of situ pulmonary hilum occlusion was applied and warm ischemia was undergone for 1 hour. 170 Sprague-Dawley rats were randomized into 3 groups: reperfusion group and reperfusion group with propofol infusion, as well as time-matched sham group. Neutrophil count

6、percent, protein concentration in BALF and malondialdehyde (MDA), superoxide dismutase(SOD), Wet/Dry (W/D) ratio in lung tissue, arterial blood gas analysis were measured at the time of 1 hour after pulmonary ischemia and 0.5h，1h，2h , 4h after reperfusion (or at the same time in time-matched sham gr

7、oup)，respectively. Apoptotic cells were stained by the terminal deoxynucleotidyl transferase-mediate dUTP nick-end labeling (TUNEL) and apoptosis index were determined. Results There were no significant differences in all parameters in these groups at the time of 1 hour after pulmonary ischemia. Com

8、pared with time-matched sham group, neutrophil count percent and protein concentration in BALF, MDA, W/D ratio and apoptosis index in lung tissue increased significantly in reperfusion group and propofol group（P0.05 or P0.01）, and SOD in lung tissue and PaO2 decreased significantly（P0.05）. Compared

9、with time-matched reperfusion group, neutrophil count percent and protein concentration in BALF, MDA, W/D ratio and apoptosis index in lung tissue decreased significantly in the group with propofol infusion（P0.05 or P0.05), but there was a tendency of improvement. Compared with time-matched reperfus

10、ion group, there was a tendency of increase in SOD in lung tissue in the reperfusion group with propofol infusion and it increased significantly at the time of 4 hours after reperfusion （P0.05）. Correlation analysis showed that apoptosis index of reperfusion group and propofol group were direct correlation with W/D ratio of corresponding group. Conclusion Propofol can attenuate ischemia-reperfusion lung injury. As inhibiting neutrophil activation and oxygen free radical